mercaptopurine and Lymphoma--Non-Hodgkin

Cancer may be a complication of inflammatory bowel disease (IBD) or its treatments. In older Crohn's disease and ulcerative colitis patients, the risk of malignancy is of particular concern. IBD diagnosis at an advanced age is associated with earlier development of colitis-associated colorectal cancer. Thiopurine use in older IBD patients is tied to an increased risk of non-Hodgkin's lymphoma, nonmelanoma skin cancer, and urinary tract cancers. Additionally, older age is accompanied by multimorbidity, an increased risk of malnutrition, and decreased life expectancy, factors that complicate the management of cancer in the elderly. The optimal approach to the increased risk of malignancy in older age IBD is appropriate cancer screening and medical treatment. This may include age-specific colorectal cancer screening and limiting UV radiation exposure. With a growing number of older IBD patients, further studies are necessary to delineate the risk of cancer in this population.

Topics: Age Factors; Aged; Colorectal Neoplasms; Early Detection of Cancer; Humans; Inflammatory Bowel Diseases; Lymphoma, Non-Hodgkin; Mercaptopurine; Skin Neoplasms; Urologic Neoplasms

Topics: Aged; Antigens, CD; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Bone Marrow; Bone Marrow Transplantation; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Daunorubicin; Dendritic Cells; Disease Progression; Doxorubicin; Humans; Immunophenotyping; Leukemia, Myelomonocytic, Acute; Lymph Nodes; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Prognosis; Remission Induction; Skin Neoplasms; Transplantation, Homologous; Vincristine

Recently, rare CD4+/CD56+ hematodermic neoplasm has been described as a distinct clinico-pathologic entity, with aggressive course and poor outcome. Skin is typically involved at presentation, but widespread dissemination to bone marrow is rapid. To date, no standardized therapeutic approach to this disease has been established. As its diffusion mainly concerns elderly patients, only a few paediatric cases have been documented. We report an additional case of CD4+/CD56+ hematodermic tumour that showed a good response to chemotherapy based on a lymphoma protocol. Moreover, we try to analyse features and outcome of a few other paediatric CD4+/CD56+ hematodermic tumours as they are reported in the literature.

Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; CD4 Antigens; CD56 Antigen; Child; Cyclophosphamide; Cytarabine; Daunorubicin; Dendritic Cells; Dexamethasone; Humans; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Prednisone; Remission Induction; Skin Neoplasms; Vincristine

Topics: Azathioprine; Bone Marrow; Drug Interactions; Drug Monitoring; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Lymphoma, Non-Hodgkin; Mercaptopurine; Methyltransferases; Structure-Activity Relationship; Thioguanine

Topics: Acute Disease; Allopurinol; Antineoplastic Agents; Child; Humans; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Mercaptopurine; Methotrexate; Prednisone; Uric Acid; Xanthine Oxidase

Skewed drug metabolism of 6-mercaptopurine (6-MP) can jeopardize antileukemic effects and result in toxicities during the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma. Allopurinol can alter 6-MP metabolism to maximize therapeutic effects while reducing toxicities. Over 75% of our patients with acute lymphoblastic leukemia or lymphoblastic lymphoma experienced a 6-MP-related toxicity. Review of metabolite date a showed 6-methylmercaptopurine nucleotide levels were >10,000 in 55% of the cohort, suggesting 6-MP shunting. Allopurinol was initiated in 12 of 23 shunters with resolution of toxicities. We propose an algorithm to incorporate allopurinol into chemotherapy regimens for patients with inappropriate 6-MP metabolism.

Topics: Adolescent; Adult; Algorithms; Allopurinol; Antimetabolites; Antimetabolites, Antineoplastic; Child; Child, Preschool; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Retrospective Studies; Young Adult

Between November 1990 and November 1996, EORTC Children Leukemia Group conducted a randomized trial in de novo acute lymphoblastic leukemia and lymphoblastic non-Hodgkin's lymphoma patients using a Berlin-Frankfurt-Munster protocol to evaluate the monthly addition of intravenous 6-mercaptopurine (i.v. 6-MP) (1 g/m(2)) to conventional continuation therapy comprising per oral MTX weekly and 6-MP daily. Only during the first 18 months of the randomization period, 6-MP p.o. was interrupted for 1 week after each i.v. 6-MP. A total of 877 patients was randomized to either no i.v. 6-MP (Arm A) or additional i.v. 6-MP (Arm B). A total of 217 relapses (91 in Group A vs 128 in Group B) and 13 deaths in CR (5 vs 8) were reported; a total of 134 patients (55 vs 79) died. The median follow-up was 7.6 years. At 8 years, the disease-free survival rate was lower (P=0.005) in Arm B (69.1% (s.e.=2.2%)) than in Arm A (77.9% (s.e.=2.0%)), and the hazard ratio was 1.45 (95% CI 1.12-1.89). In conclusion, as delivered in this study, i.v. 6-MP was detrimental to event-free survival.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Evaluation Studies as Topic; Female; Humans; Infant; Injections, Intravenous; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Patient Compliance; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Reproducibility of Results; Treatment Outcome

We report here on treatment results of consecutive CCLSG NHL studies (NHL855, 1985-1989; NHL890, 1989-1996). The NHL855 protocol consisted of an induction phase of five drugs (VCR, PRD, CPM, DXR, and high-dose MTX) and a maintenance phase of 7 drugs. The probabilities of EFS at 7 years were 78% (SE, 10%) for the patients with localized disease, and 38% (SE, 7%) for those with advanced disease. In the NHL 890 protocol, the patients were assigned to two different treatment groups according to their histology and received different consolidation therapy; non-lymphoblastic subtype was treated almost identically to NHL855 while LASP and VP-16 were newly added for the lymphoblastic subtype. The 7-year EFS improved to 91% (SE, 6%) for localized disease, and 61% (SE, 6%) for advanced disease. A remarkable improvement was particularly evident for lymphoblastic type with mediastinal mass. Optional trial of high-dose sequential chemotherapy and peripheral blood progenitor cell auto grafting resulted in an unfavorable outcome. The 7-year EFS according to main histological subgroups were as follows: 84% (10%) for large cell type, 67% (11%) for Burkitt's-type, 58% (10%) for lymphoblastic type. Secondary cancer occurred in two of the 163 patients studied. Both patients were AML (M0/M4) and MLL rearrangement was detected in the M4 case.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Doxorubicin; Etoposide; Female; Follow-Up Studies; Humans; Hydrocortisone; Infant; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Neoplasms, Second Primary; Prednisolone; Remission Induction; Treatment Outcome; Vincristine

Children and young adults with early-stage non-Hodgkin's lymphoma have an excellent prognosis, but treatment is prolonged and is associated with many side effects. We performed two studies to determine whether therapy could be simplified.. Between 1983 and 1991, we conducted two consecutive trials in children and young adults (age, <21 years) with early-stage non-Hodgkin's lymphoma. In the first trial, patients were treated for 9 weeks with induction chemotherapy consisting of vincristine, doxorubicin, cyclophosphamide, and prednisone, followed by 24 weeks of continuation chemotherapy with mercaptopurine and methotrexate. Half the patients were randomly assigned to receive involved-field irradiation. In the second trial, after the 9 weeks of induction chemotherapy, the patients were randomly assigned to receive 24 weeks of continuation chemotherapy or no further therapy.. A total of 340 patients were enrolled in the two trials, 12 of whom did not have complete remissions. One hundred thirteen patients received nine weeks of chemotherapy without radiotherapy, 131 received eight months of chemotherapy without radiotherapy, and 67 received eight months of chemotherapy with radiotherapy. At five years, the projected rates of continuous complete remission were 89, 86, and 88 percent for the three groups, respectively. At five years, event-free survival among the patients with early-stage lymphoblastic lymphoma was inferior to that among the patients with other subtypes of lymphoma (63 percent vs. 88 percent, P<0.001). Continuation therapy was effective only in patients with lymphoblastic lymphoma.. A nine-week chemotherapy regimen without irradiation of the primary sites of involvement is adequate therapy for most children and young adults with early-stage, nonlymphoblastic non-Hodgkin's lymphoma.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Female; Humans; Infant; Life Tables; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Prednisone; Remission Induction; Research Design; Survival Analysis; Vincristine

Standard prophylaxis and treatment of malignancy-associated hyperuricemia in the USA has been allopurinol with vigorous hydration, urinary alkalinization and osmotic diuresis. Urate oxidase, the enzyme that converts uric acid to allantoin (a readily excreted metabolite that has 5- to 10-fold higher solubility than uric acid), is an alternative therapy; however, few published findings support this practice. Between February 1994 and December 1996, we administered non-recombinant urate oxidase (Uricozyme) to 126 children with newly diagnosed non-B cell acute lymphoblastic leukemia (ALL) during the first 5 days of chemotherapy with methotrexate, 6-mercaptopurine or both. Their blood levels of uric acid and other indicators of tumor lysis were measured at diagnosis and during treatment and then compared with findings in 129 similarly treated historical controls who had received allopurinol to control hyperuricemia. Clinical responses to urate oxidase were also determined in eight patients with newly diagnosed B cell ALL or advanced-stage non-Hodgkin lymphoma. Patients treated with urate oxidase had rapid and significantly greater decreases in their blood uric acid levels than did the historical controls (median maximal level during treatment, 2.3 vs 3.9 mg/dl, P < 0.001). They also had lower creatinine (0.6 vs 0.7 mg/dl, P = 0.01) and blood urea nitrogen (11 vs 24 mg/dl, P < 0.001) levels. Similar findings were made in the eight cases of B cell ALL or non-Hodgkin lymphoma. None of the patients required dialysis for acute renal failure. Six (4.5%) of the 134 children given urate oxidase had allergic reactions, manifested primarily by urticaria, bronchospasm and hypoxemia. Thus, non-recombinant urate oxidase is a more effective uricolytic agent than allopurinol but is associated with acute hypersensitivity reactions, even in patients without a history of allergy.

Topics: Allopurinol; Antimetabolites; Antineoplastic Agents; Child; Child, Preschool; Female; Humans; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Time Factors; Urate Oxidase; Uric Acid

We investigated the metabolism of high dose 6 mercaptopurine (HD-6MP) infusions and its influence on the metabolism by allopurinol, an inhibitor of xanthine oxidase, the enzyme that catabolizes 6MP into thioxanthine and thiouric acid.. Nine patients (aged 2-11 years) with non-Hodgkin lymphoma (NHL) were treated with HD-6MP (1300 mg/m(2).24h) within a therapeutic window after diagnosis. Four patients received oral allopurinol (200 mg/m(2).day) to prevent urate nephropathy, and five did not. Plasma and RBC were isolated before and 4, 20, 24, 28, and 48h after the start of the infusion. All measurements were performed with HPLC.. Considerable variations were found in the plasma levels of 6MP, thioxanthine, and thiouric acid and of RBC-MeTIN levels. 6MP-riboside was not detectable, and MeMP and MeMPR levels were <1.3 muM in the plasma. In general, 6MP, thioxanthine, and MeMP levels in plasma were higher, and thiouric acid plasma levels and RBC-MeTIN levels were lower in the patients treated with allopurinol compared to those who did not receive allopurinol.. 6MP is extensively metabolized in patients with NHL treated with HD-6MP. Thiopurine methylation, at the levels of nucleotide, nucleoside, and base, is an important metabolic pathway after HD-6MP. Co-administration of allopurinol can result in both a decreased catabolism and anabolism of 6MP compared to treatment with HD-6MP alone. This observation may have consequences for the therapeutic efficacy and toxic effects of 6MP in combination with allopurinol.

Topics: Allopurinol; Antimetabolites, Antineoplastic; Antineoplastic Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Enzyme Inhibitors; Erythrocytes; Female; Humans; Hypoxanthine; Hypoxanthines; Individuality; Infusions, Intravenous; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methylthioinosine; Nucleotides; Xanthine; Xanthine Oxidase; Xanthines

From 1985 to 1989, 69 patients with non-Hodgkin's lymphoma (NHL) were treated by members of the Children's Cancer and Leukemia Study Group of Japan with a protocol consisting of vincristine, prednisolone, cyclophosphamide, doxorubicin, high-dose methotrexate (HD-MTX), mercaptopurine and cytarabine; central nervous system (CNS) prophylaxis with intrathecal MTX and hydrocortisone (NHL855). The 4-year event-free survival (EFS) was 78% (S.E., 10%) for patients with localized disease (n = 18) and 38% (S.E., 7%) for those with advanced disease (n = 51). Among the patients with advanced disease, those with non-lymphoblastic lymphoma tended to have a better 4-year EFS than those with lymphoblastic lymphoma (52% vs. 25%). Based on these findings, we initiated a new protocol NHL890 in which patients were assigned to two different chemotherapies according to the histology. Non-lymphoblastic subtype was treated almost identically to NHL855 while asparaginase and VP-16 were newly added in the consolidation-maintenance phase in advanced-stage lymphoblastic lymphoma. Sixty-seven patients with advanced disease were assessable. The overall 4-year EFS for advanced disease improved to 69% (S.E., 6%). A significant improvement was gained in the lymphoblastic lymphoma with a 4-year EFS of 56% (S.E., 11%) as compared with 25% (S.E., 9%) in the preceding study (P < 0.05). These findings suggest the importance of histology in the treatment of advanced-stage non-Hodgkin's lymphoma in childhood.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Doxorubicin; Etoposide; Female; Humans; Hydrocortisone; Infant; Japan; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Prednisolone; Remission Induction; Vincristine

Seventy-three patients with Stage III abdominal non-Hodgkin's lymphoma were prospectively treated following two sequential protocols (P): L278 P (group A, 33 patients) (1978-1983) and L384 P (group B, 40 patients), (1984-1991). No patient received radiotherapy. The L278 P included 7 drugs: cyclophosphamide, vincristine (VCR), adriamycin (ADR), prednisone, methotrexate (MTX), dexamethasone, and 6-mercaptopurine, given for remission induction, maintenance, and CNS prophylaxis. In the L384 P we introduced a consolidation phase consisting of intravenous MTX and citrovorum factor rescue, and IV cytosine arabinoside. VCR was also added to the monthly doses and the maintenance phase was reduced from 18 to 15 months. From January 1988 we changed ADR for epirubicin in the same doses. Prophylactic treatment of the CNS, in the L384 P, was intensified by increasing the number of doses of MTX IT in the remission, induction, and consolidation phases, and with the use of ara-C IT. Laparotomy in 50 patients allowed partial resection in 16, and second-look laparotomy was performed in 27 patients. Viable tumor was found in four patients. Three patients (G-A) died from metabolic complications and another 4 (2 G-A and 2 G-B) failed to attain CR and died. A total of 28 (85%) of 33 children of G-A and 38 (95%) of 40 children in G-B achieved CR. Five children died in remission (2 G-A, 3 G-B). Three patients (G-A) relapsed in the CNS and one (G-B) relapsed in the abdomen and died. Disease-free survival at 120 months was 70% in G-A and 84% in G-B.

Topics: Abdominal Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Neoplasms; Child; Child, Preschool; Costa Rica; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Female; Humans; Infusions, Intravenous; Leucovorin; Life Tables; Lymphatic Metastasis; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Neoplasm Recurrence, Local; Prednisone; Prospective Studies; Remission Induction; Survival Rate; Vincristine

In order to evaluate the role of Mitoxantrone in the therapy of non-Hodgkin's lymphoma (NHL) (intermediate-high grade malignancy) a series of successive phase II-III studies were performed in a multicenter cooperative group. The first phase II study consisted of Mitoxantrone alone administered at 14 mg/m2 i.v. on day 1 and repeated every 3 weeks for six times. Fifteen refractory or relapsed patients (pts) entered the study, and an overall response of 54% (CR 4 pts, PR 4 pts) was obtained. 7 pts progressed or remained stable disease (NR). The second phase II consisted of Mitoxantrone in combination with Etoposide and Prednisone (VeMP). Twenty pts were treated and a complete remission (CR) of 50% with 1 partial remission (PR) were obtained with an overall response of 55%. The third phase II study consisted of 13 pts with refractory or relapsed disease treated with Mitoxantrone, Cis-platinum, Etoposide and Prednisone (CEMP); an overall response of 62% was obtained with an acceptable toxicity. This was not superior to other conventional salvage regimens. On this background a phase III study with VEMP (Etoposide, Cyclophosphamide, Mitoxantrone, Prednisone) was started as first line therapy for pts presenting one or more of following criteria: Performance Status (P.S.) 2-3, aggressive histology at stage I-IIE or advanced stage in old pts, low grade histology with B-symptoms stage in III-IV, age over 65 years. Until now 64 pts entered this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Cyclophosphamide; Drug Administration Schedule; Etoposide; Female; Gastrointestinal Diseases; Humans; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Middle Aged; Mitoxantrone; Prednisolone; Prednisone; Remission Induction; Salvage Therapy; Survival Analysis; Treatment Outcome; Vincristine

For over 30 years, oral 6-mercaptopurine (6-MP) has been a mainstay of systemic maintenance therapy for acute lymphoblastic leukemia. Despite its efficacy as an antileukemic agent, 6-MP has not been previously administered by the intrathecal (IT) route. In anticipation of a clinical trial of IT 6-MP, preclinical cytotoxicity and pharmacology studies were performed to define a safe, effective dose. The optimal concentration (greater than 1 microM) and duration of exposure (greater than 12 h) to 6-MP required for cytotoxicity were determined in vitro using human leukemia cell lines. The dose required to achieve the desired cerebrospinal fluid concentrations in humans was derived from pharmacokinetic parameters determined in rhesus monkeys. A phase I/II study was then performed in pediatric patients with refractory meningeal leukemia. Nine patients (aged 3.5 to 16 years) with chronic meningeal leukemia (2 to 6 central nervous system relapses) were entered onto the study. All had previously failed, at a minimum, IT methotrexate, IT cytarabine, and cranial (+/- spinal) radiation. A 10-mg IT dose of 6-MP (calculated to produce cytotoxic cerebrospinal fluid levels for 12 h) was administered twice weekly for 4 weeks. There were four complete responses and three partial responses. The duration of complete responses ranged from 7 to 22 weeks. Observed toxicities were not dose limiting and included mild headache (three patients) and minimal nausea (two patients). Pharmacokinetic studies performed in patients confirmed that cerebrospinal fluid concentrations of 6-MP were greater than 1 microM for 12 h. These results indicate that the IT administration of 6-MP is feasible, is not associated with significant toxicity, and has definite activity in patients with refractory meningeal leukemia.

Topics: Adolescent; Animals; Child; Child, Preschool; Drug Evaluation; Female; Humans; Injections, Spinal; Leukemia; Lymphoma, Non-Hodgkin; Macaca mulatta; Male; Meningeal Neoplasms; Mercaptopurine; Tumor Cells, Cultured

We report the safety and efficacy of 34 consecutive autologous bone marrow transplant (ABMT) procedures performed in adult patients with high-grade lymphoid malignancy after remission induction therapy. Fifteen patients with acute lymphoblastic leukemia (ALL) and six with high-grade non-Hodgkin's lymphoma (NHL) received pretransplant conditioning with intravenous (IV) melphalan and fractionated total body irradiation (TBI). Thirteen other patients with NHL were conditioned with melphalan alone, having previously received local involved field radiotherapy. Unmanipulated noncryopreserved autologous marrow was reinfused within 48 hours of harvesting. Engraftment occurred in all patients with medians of 10 days of neutropenia (neutrophils less than 0.5 x 10(9)/L), 4-day platelet transfusion requirement, 3 U packed RBC transfusion, and 18 days in hospital posttransplant. There were no procedure-related deaths. Actuarial disease-free survival in the 13 patients with ALL receiving autotransplant early in first remission is 48% with a median follow-up of 3 years. Two other ALL patients who had autotransplants after a period of maintenance therapy also remain in complete remission (CR). These results compare favorably with our 34% disease-free survival (DFS) in 15 allogeneic ALL transplant patients and 21% DFS in 19 patients on standard maintenance after a common induction schedule. No relapses have occurred in the 17 NHL patients transplanted in remission (median follow-up 2 years), but the two NHL patients who developed recurrent disease before ABMT died of progressive disease after temporary responses. We conclude that this method of ABMT results in rapid reengraftment with lack of toxicity and that the conditioning treatment used shows good efficacy against disease. It is applicable in high-grade lymphoid malignancy in first remission, and our results call into question the need for marrow purging in ALL and NHL patients transplanted in first remission.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Combined Modality Therapy; Cryopreservation; Female; Follow-Up Studies; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Mercaptopurine; Methotrexate; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Transplantation, Autologous

The histological diagnosis of non-Hodgkin's lymphoma (Burkitt's lymphoma excluded) in 147 children was reviewed. The most common site of presentation was in the abdomen (32.6%). The most frequent site of metastatic disease at diagnosis was the bone marrow (27.2%). The most common histology was diffuse undifferentiated non-Burkitt type (37.4%). According to the Murphy staging system, 40.1% were stage III and 27.2% were stage IV. In a nonrandomized prospective study, 121 patients were submitted to a treatment regimen (protocol 8001) and compared with 26 historical controls treated with the COP regimen, consisting of cyclophosphamide, vincristine, and prednisone. Of those patients treated with protocol 8001, nine had intestinal perforation at the site of primary disease. All patients in this group were malnourished at the time of perforation. The overall rate of initial complete remission in those patients treated with protocol 8001 was 90.7%. The duration of remission was from 16 to 108 months, with a median of 39 months. The actuarial rate of disease-free survival was 69% at 2 years and 63% at 6 years, compared with 36% at 6 years of the control group (COP) (p less than 0.01). None of the patients have relapsed after 4 years.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Child, Preschool; Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Female; Humans; Hydrocortisone; Intestinal Perforation; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Nutrition Disorders; Prednisone; Vincristine

Patients with inflammatory bowel diseases may have higher incidences of non-melanoma skin cancers and non-Hodgkin lymphoma, potentially linked to underlying disease and treatments. This analysis assessed incidence rates of these malignancies in Japanese patients with ulcerative colitis or Crohn's disease, and their association with thiopurine and/or anti-tumor necrosis factor-α treatment, using data from a nationwide administrative database in Japan.. Patients diagnosed with inflammatory bowel disease without malignancy were identified from the Medical Data Vision database. Incident cases of non-melanoma skin cancers and non-Hodgkin lymphoma diagnosed after prescription of thiopurine and/or anti-tumor necrosis factor-α were identified between April 2008 and January 2018. Age- and sex-adjusted incidence rate ratios were calculated relative to the total treated patient population.. A total of 75 673 eligible patients were identified at the index date. Thiopurine prescription with or without anti-tumor necrosis factor-α agents increased incidence rate ratios for non-melanoma skin cancers relative to the overall population (3.39 and 4.03, respectively). There were no notable differences in non-Hodgkin lymphoma incidence relative to the total population in any treatment subgroup, regardless of prescription of thiopurine and/or anti-tumor necrosis factor-α (all incidence rate ratios, ~1).. There is no evidence for an increased incidence of non-Hodgkin lymphoma attributable to thiopurine or anti-tumor necrosis factor-α treatment in Japanese patients with inflammatory bowel disease. The impact of racial differences on non-Hodgkin lymphoma incidences should be considered. Thiopurine therapy may be a risk factor for non-melanoma skin cancers in Japanese patients.

Topics: Adalimumab; Adult; Aged; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Colitis, Ulcerative; Crohn Disease; Cross-Sectional Studies; Databases, Factual; Drug Therapy, Combination; Female; Gastrointestinal Agents; Humans; Immunosuppressive Agents; Incidence; Infliximab; Japan; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Middle Aged; Proportional Hazards Models; Risk Factors; Skin Neoplasms; Tumor Necrosis Factor-alpha

Crohn's disease (CD) patients may be at increased risk for the development of Hodgkin's lymphoma (HL) or non-Hodgkin's lymphoma (NHL), either through exposure to immunosuppressive medications or due to their underlying chronic inflammatory illness. There are limited data regarding the natural history of CD following treatment of lymphoma. We present a series of CD patients who were treated for lymphoma and describe the natural history of their CD following lymphoma treatment.. Retrospective case series from three academic referral centers was used. All CD patients with a history of lymphoma were identified. Demographic data, CD medication exposure, and surgical procedures before and after lymphoma treatment were recorded.. Nine CD patients with a history of lymphoma were identified. Eight individuals received chemotherapy, while one patient was observed without treatment. Eight patients remained free of lymphoma for a mean of 72.8 months (range 1-276 months). The ninth patient had recurrence of his HL 3 years after lymphoma diagnosis. Following lymphoma treatment, two patients had quiescent CD with no specific therapy. Three patients demonstrated significant clinical relapse of their CD and a fourth patient developed CD after treatment of her lymphoma, which ultimately required long-term immunomodulator therapy with 6-mercaptopurine or methotrexate in the first three patients, and azathioprine in the fourth. Four patients required CD surgery after lymphoma treatment.. We report on the clinical course of CD in patients who develop lymphoma. Significant clinical relapse of CD following successful medical treatment of lymphoma occurred frequently in patients with a history of this neoplasm.

Topics: Adolescent; Adult; Antineoplastic Agents; Child; Crohn Disease; Female; Hodgkin Disease; Humans; Immunosuppressive Agents; Lymphoma; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Middle Aged; Retrospective Studies; Treatment Outcome; Young Adult

To explore the DNA incorporation of 6-thioguanine nucleotide levels (DNA-6TGN) during 6-mercaptopurine (6MP) therapy of childhood acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma (NHL) and its relation to erythrocyte levels of their metabolites: 6-thioguanine-nucleotides (E-6TGN), methylated metabolites (E-MeMP), Methotrexate polyglutamates (E-MTX), and to thiopurine methyltransferase activity (TPMT).. We studied these metabolites in 229 blood samples from 18 children with ALL (N = 16) or NHL (N = 2) on 6MP/Methotrexate maintenance therapy.. DNA-6TGN levels were significantly correlated to E-6TGN (r (p) = 0.66, p = 0.003) with a trend to reach a plateau at high E-6TGN levels. To explore the relative DNA incorporation of 6TGN in relation to cytosol 6TGN levels, a DNA-6TGN index was calculated as DNA-6TGN/E-6TGN. The DNA-6TGN index was inversely correlated to E-6TGN (r (p) = -0.58, p = 0.012), which implies that with increasing levels of E-6TGN relatively less 6TGN are incorporated into DNA. E-MeMP levels were correlated to the DNA-TGN index (r (p) = 0.60, p = 0.008), indicating that high levels of MeMP result in enhanced DNA-6TGN incorporation, possibly due to inhibition of purine de novo synthesis, mediated by some of the methylated 6MP metabolites.. DNA-6TGN may prove to be a more relevant pharmacokinetic parameter for monitoring 6MP treatment intensity than the previously used erythrocyte 6MP metabolites levels. Prospective clinical trials are needed to evaluate the usefulness of DNA-6TGN for individual dose adjustments.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cytosol; DNA; Drug Monitoring; Erythrocytes; Female; Guanine Nucleotides; Humans; Infant; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Purines; Thionucleotides

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cyclosporine; Cytarabine; Female; Histiocytosis, Langerhans-Cell; Humans; Lymphoma, Non-Hodgkin; Mercaptopurine; Methotrexate; Prednisolone; Prednisone; Vinblastine; Vincristine

Effectiveness and toxicity of childhood cancer treatments have never been evaluated in Kenya since introduction of structured care in the early seventies.. To evaluate effectiveness and toxicity of two treatment protocols for Non-Hodgkin's lymphoma (NHL).. Historical cohort study using medical records.. Kenyatta National Hospital, a tertiary care and medical teaching hospital.. Children < or =15 years with diagnosis of non-Hodgkin's Lymphoma.. Primary outcomes were median survival, event free survival and toxicity.. Out of 101 records, only 26 (25.7%) met inclusion criteria. Baseline characteristics were similar in the two treatment arms. Median survival was 0.75 months (95% CI = 0.54-0.96) and 1.0 months (95% CI = 0.29-1.71) for short and long arm groups. There was no difference in event free survival and haematological toxicity.. No clear difference in effectiveness and toxicity between the intensive-short and the less aggressive long course chemotherapy regimens was evident. Though lack of difference may be attributed to the small sample size, suboptimal supportive care for intensive treatment would increase risk of toxic deaths. As the short course protocol did not demonstrate obvious deterioration of median and event free survival, a strong case may be made for a randomised clinical trial within a context of improved supportive care.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Cyclophosphamide; Cytarabine; Disease-Free Survival; Doxorubicin; Female; Humans; Kenya; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Prednisone; Retrospective Studies; Treatment Outcome; Vincristine

Avascular necrosis (avn) is a complication of treatment for malignancies in children and adolescents. The authors present a two-center retrospective of experiences with avn in children treated for acute lymphoblastic leukaemia or non-Hodgkin lymphoma (8 from 191 patients with newly diagnosed disease in total of 19 sites). The median age at diagnosis was 16.6 years. Avn was observed in 4.1% of the group, higher among males than females (7/1), both during and after therapy. Early diagnosis of the process has enabled 7 patients to avoid surgical intervention. The increased incidence of avn, the multimodal character of symptoms, but unknown late consequences of avn showed that prospective studies of early recognition and proper therapy are needed.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Female; Humans; Incidence; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Osteonecrosis; Poland; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Prednisone; Retrospective Studies; Vincristine

We analysed the impact of age and gender on biology and outcome of 2084 patients diagnosed with non-Hodgkin lymphoma (NHL) between October 1986 and December 2002 and treated according to the Berlin-Frankfurt-Münster (BFM) multicentre protocols NHL-BFM-86, -90 and -95. Median age at diagnosis was 8.0 years for 97 precursor B-lymphoblastic lymphoma (pB-LBL) patients, 8.8 years for 335 T-lymphoblastic lymphoma (T-LBL) patients, 8.4 years for 1004 Burkitt's lymphoma/leukaemia (BL/B-AL) patients, 11.4 years for 173 diffuse large B-cell lymphoma (centroblastic subtype) (DLBCL-CB) patients, 13.2 years for 40 primary mediastinal large B-cell lymphoma (PMLBL) patients and 10.8 years for 215 anaplastic large-cell lymphoma (ALCL) patients (P < 0.00001). The male:female ratio was 0.9:1 for pB-LBL and PMLBL, 1.7:1 for DLBCL-CB, 1.8:1 for ALCL, 2.5:1 for T-LBL and 4.5:1 for BL/B-AL (P < 0.00001). The probability of event-free survival at 5 years (5-year pEFS) was 85 +/- 1% for all 2084 patients [median follow-up 5.7 (0.1-15.9) years], and was significantly superior for male T-LBL and DLBCL-CB patients. Comparing age-groups 0-4, 5-9, 10-14 and 15-18 years, pEFS was inferior for the youngest patients only in the pB-LBL- and ALCL-groups. T-LBL and DLBCL-CB adolescent females had worse outcome than younger girls while age had no impact on pEFS for boys. We conclude that the distribution of age and gender differed between NHL-subtypes. The impact of gender on outcome differed between NHL subgroups. The prognostic impact of age differed not only by NHL-subtype but also according to gender in some subtypes.

Topics: Adolescent; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Disease-Free Survival; Female; Humans; Infant; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Multivariate Analysis; Prednisone; Regression Analysis; Sex Factors; Survival Rate; Vincristine

Angiogenesis is an important mechanism in morbility of malignant tumor, vascular endothelial growth factor (VEGF) is the key factor. This study was to investigate the serum level of VEGF in children and adolescent patients with non-Hodgkin's lymphoma (NHL).. The serum levels of VEGF(sVEGF) in 24 pretreated NHL patients were detected by ELISA. sVEGF in 10 of the 24 patients who received complete response after treatment were also detected by ELISA.. The average serum VEGF level was 745.79 ng/L (40.64-3623.09 ng/L)in 24 NHL patients. It was higher than normal [(294.20+/-23.40) ng/L]. sVEGF in 18 of the patients were higher than the standard, while in 6 of the patients were lower than the standard. The average serum VEGF level was 289.54 ng/L (35.11-826.8 ng/L) in 10 of The CR patients, 8 cases of them had a high VEGF level before treatment but a nearly normal level after first CR. And 2 cases of them had normal level during the course.. The serum level of VEGF in NHL patients was higher than normals. The high serum level of VEGF has a tendency to drop to the normal standard after receiving CR. From the clinical data, a high serum level was not found associated with stage, gender, PS. score, IPI score, serum LDH and "B" symptoms et al.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Burkitt Lymphoma; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Female; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Remission Induction; Vascular Endothelial Growth Factor A; Vincristine

Non-Hodgkin lymphomas (NHL) in children are the second most common malignant tumors in Kuwait. Until 1995 the patients (pts) received institutional protocols. From October 1995 to September 2000 21 children with NHL were treated. Five children were treated by NHL BFM 90 protocol, 7 pts received NHL BFM 95 scheme, and 9 children underwent therapy abroad or according to different types of protocols. The results of a retrospective analysis of NHL BFM 95 protocol in Kuwait are reported. Seven patients diagnosed with NHL--group B: 3 children with Burkitt lymphoma (B-cell NHL) and group A: 4 children with lymphoblastic lymphoma (T-cell NHL)--were treated from October 1995 to September 2000 in the Kuwait Cancer Control Centre according to NHL BFM 95 protocol. Group B consisted of 2 girls and 1 boy; median age at diagnosis was 4 years 8 months, 2 pts classified as stage II and 1 pt as stage III. All patients were assigned to risk group R2. Median follow-up is 2 years 8 months. Group A included 1 girl and 3 boys; median age at diagnosis was 5 years 8 months, 1 pt classified as stage III and 3 pts as stage IV. All patients were assigned to IR group. Median follow-up is 3 years 6 months. In group B all 3 pts are in 1st CR; in group A 3 pts are in 1st CR and 1 pt having Li-Fraumani syndrome died after the 3rd relapse of disease during therapy. In both groups there was no toxic death, myelotoxicity WHO grade III-IV, hepatotoxicity WHO grade II-III. Treatment results of NHL BFM 95 study in our small group of patients are very optimistic. Six patients are in 1st CR and one died due to progression of disease. Despite the small group of patients, the results suggest that NHL BFM 95 protocol is highly effective and safe with regular supportive care.

Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Burkitt Lymphoma; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Doxorubicin; Drug Administration Schedule; Etoposide; Female; Follow-Up Studies; Humans; Ifosfamide; Infant; Kuwait; Leucovorin; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Male; Mercaptopurine; Mesna; Methotrexate; Neoplasm Staging; Prednisolone; Prednisone; Survival Rate; Thioguanine; Treatment Outcome; Vincristine

We describe a 69-year-old Japanese male with acute leukemia with a CD7+ and CD56+ immunophenotype presenting with multiple lymphadenopathy. He was treated with idarubicin and cytosine arabinoside. Although the leukemia showed partial response, the patient did not achieve complete remission. He died of sepsis due to severe neutropenia after the third course of chemotherapy. His autopsy revealed blast infiltration in the lymph nodes, liver, spleen and vertebral bone marrow. Recently, CD7+ and CD56+ myeloid/natural killer precursor acute leukemia has been associated with a poor prognosis. Our case illustrates that myeloid/natural killer cell precursor acute leukemia shows some response to intensive chemotherapy for acute myeloid leukemia, but such therapy is insufficient to effect a cure. To overcome the resistance of this disease to chemotherapy, further studies should explore other treatment strategies.

Topics: Acute Disease; Aged; Antigens, CD; Antigens, CD7; Antigens, Differentiation, Myelomonocytic; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; CD56 Antigen; Cytarabine; Daunorubicin; Diagnosis, Differential; Etoposide; Fatal Outcome; Humans; Idarubicin; Killer Cells, Natural; Leukemia, Myeloid; Leukemic Infiltration; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Mitoxantrone; Myeloid Cells; Neoplastic Stem Cells; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sarcoma, Myeloid; Sialic Acid Binding Ig-like Lectin 3

The purpose of this study was to determine the frequency with which magnetic resonance (MR) imaging detects avascular necrosis of the bone (AVNB) in children with acute lymphoblastic leukemia (ALL) or advanced-stage non-Hodgkin lymphoma (NHL) who receive prednisone during remission induction, reinduction, and maintenance chemotherapy; to assess the clinical significance of these findings; and to identify factors predictive of AVNB. We prospectively obtained MR imaging of the hips and knees of 116 children who had completed at least 1 year of treatment for ALL or advanced-stage NHL on identical prednisone-containing regimens between December 1991 and October 1994. MR imaging findings of AVNB were compared with clinical outcomes, and the effect of therapeutic and patient factors on the frequency of AVNB was analyzed. The MR imaging findings of 17 of the 116 participating patients were consistent with AVNB. The most common clinical manifestation was joint pain (11 patients). Only one patient had progressive joint deterioration that necessitated surgical replacement. Only age 10 years or more at the time of the primary diagnosis was significantly associated with the development of AVNB (P = 0.004). MR imaging showed changes consistent with AVNB in approximately 15% of this patient population. However, most patients in this study who had MR imaging signs of AVNB did not experience progressive joint destruction, even with continued prednisone therapy. Therefore, the clinical usefulness of MR imaging as a screening tool for AVNB in this set of patients remains uncertain.

Topics: Adolescent; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Arthralgia; Arthroplasty, Replacement, Hip; Asparaginase; Child; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Etoposide; Female; Femur Head Necrosis; Humans; Lymphoma, Non-Hodgkin; Magnetic Resonance Imaging; Male; Mercaptopurine; Methotrexate; Mitoxantrone; Osteonecrosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Risk Factors; Treatment Outcome; Vincristine

Most complications of 6-mercaptopurine (6MP) used in the treatment of inflammatory bowel disease (IBD) occur early, whereas neoplasms occur late in the course. Concern persists that the risk is increased when 6MP is used. We report our experience with malignant tumors developing over 27 yr of treating IBD patients with 6MP.. A total of 591 patients with IBD treated with 6MP between 1969 and 1997 were followed or traced until present to identify all malignant tumors and blood dyscrasias that had developed to determine the type, distribution, and duration of the IBD, the dose and duration of 6MP therapy, the concurrent versus previous use of 6MP, the incidence and probable relationship of 6MP to specific neoplasms, and whether the 6MP had been effective in treatment.. A total of 550 patients (93%) fulfilled the criteria for follow-up; these included 380 with Crohn's disease (CD) and 170 with ulcerative colitis (UC). Twenty-five patients had developed neoplasms (16 of 380 CD and nine of 170 UC) (p = 0.66). In half of the cases, the goal of therapy had been achieved with 6MP. In 10 patients, the neoplasm was diagnosed while the patients were taking 6MP (40%) and in 15, many years after the 6MP had been terminated (60%). The incidence of neoplasms (25 of 550) was 2.7/1000 patient-years of follow-up. The most common neoplasms were found in the bowel (eight of 550, 1.6%; five CD, and three UC), and breast (three, 0.5%; two CD, and one UC). Non-Hodgkins lymphomas occurred in two patients with CD; one was cerebral and the other abdominal. One patient with CD developed leukemia. The duration of 6MP therapy ranged from 5 months to 22 yr, with a mean of 5 yr. The dose of 6MP ranged from a quarter of a tablet/day (12.5 mg) to 100 mg/day, with the majority in a range from 50 to 75 mg/day.. In no instance could a neoplasm be attributed to the use of 6MP. The incidence of colon cancer is not greater than that with long standing colitis. Suspicion of a relationship between 6MP and leukemia/lymphoma persists, but the incidence is low. This must be weighed against the improved quality of life due to 6MP for patients with IBD.

Topics: Abdominal Neoplasms; Adult; Aged; Aged, 80 and over; Brain Neoplasms; Breast Neoplasms; Colitis, Ulcerative; Crohn Disease; Drug Administration Schedule; Female; Follow-Up Studies; Hematologic Diseases; Humans; Immunosuppressive Agents; Incidence; Inflammatory Bowel Diseases; Intestinal Neoplasms; Leukemia; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Middle Aged; Neoplasms; Risk Factors; Time Factors

The aim of the study was to evaluate the results of treatment of 46 children with non B non-Hodgkin's Lymphoma registered in 7 centers of Polish Paediatric Leukaemia/Lymphoma Study Group from 1993 to 1998. The patients were treated according to BFM-90 protocol based on German regimen. The overall probability of event-free survival for the all children after 4 years of follow-up was 71%, for patients in stage III--65%, stage IV--70%. The achieved results were not as positive as in the BFM Study Group, what was related to: the great number of children with advanced stage of disease (54.3%), the late final diagnosis, the great number of recurrences (22.5%) and deaths caused by the toxicity of medication (6.5%) (infections, drug toxicity).

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Female; Follow-Up Studies; Humans; Infant; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Neoplasm Staging; Poland; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Retrospective Studies; Survival Rate; Treatment Failure; Vincristine

Endocrine dysfunction and damage of the epiphysial growth plates have been reported as late effects of antileukaemic treatment during childhood. It is a common opinion that cranial irradiation (CI) is the most important factor for blunted growth. Accordingly, recent therapeutic strategies in acute lymphoblastic leukaemia (ALL) avoid cranial irradiation. Here we analysed longitudinal data on growth and puberty of 54 children in first complete remission, who were treated with 18 Gy CI or not submitted to radiotherapy. Two chemotherapeutic protocols were compared which were similar during the induction period but differed in the intensity of maintenance therapy. In cranial irradiated patients both in males and females the pubertal growth spurt started at a mean age of 1.2 years (SD: 0.93 years) earlier than controls. Age at diagnosis and age at pubertal growth spurt were significantly correlated (r = 0.35, P = 0.017). Similarly, menarche occurred at a mean age (n = 22) of 12.1 years and was correlated with the age at start of therapy in girls who were treated with 18 Gy CI (r = 0.61, P = 0.01). Adult height was reached spontaneously in 30 patients treated during prepubertal age and in 10 treated shortly before or during puberty. In all prepubertal patients treated for 2-3 years with intensive maintenance therapy blunted growth resulted in a significant loss of -1.85 H-SDS (median, P = 0.0051) compared to height at diagnosis. However, if continuation treatment used only methotrexate and 6-mercaptopurine (i.e. BFM protocol) final height equalled projected adult height, despite 18 Gy CI.. (1) multiagent chemotherapy is of major impact for growth and puberty; (2) 18 Gy cranial irradiation is below the critical dosage responsible for blunted growth; (3) loss in potential growth might be prevented by current CT strategies; (4) onset of puberty depends on age when antileukaemic therapy is applied.

Topics: Adolescent; Age Factors; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Case-Control Studies; Combined Modality Therapy; Cranial Irradiation; Dose-Response Relationship, Radiation; Female; Growth; Growth Disorders; Humans; Longitudinal Studies; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Puberty

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Combined Modality Therapy; Humans; Lymphoma, Non-Hodgkin; Mercaptopurine; Methotrexate; Survival Rate

Topics: Child; Child, Preschool; Dose-Response Relationship, Drug; Humans; Lymphoma, Non-Hodgkin; Mercaptopurine; Tumor Lysis Syndrome

Thirty-nine consecutive children (age, 2 to 11 years) with nonlymphoblastic (NL) lymphomas were treated uniformly with chemotherapy based on the LNH-II-85 protocol. The protocol consisted of a remission-induction phase that lasted 30 days and started with cyclophosphamide (CTX) 1.2 g/m2 on day 1, followed by vincristine (VCR) 1.5 mg/m2 on days 3, 10, 17, and 24, daunomycin (DAUNO) 60 mg/m2 on days 12 and 13, and prednisone 40 mg/m2/d for 30 days. If a complete remission was achieved, an intensification regimen was given that consisted of eight courses of teniposide (VM-26) 165 mg/m2 plus cytarabine (ARA-C) 300 mg/m2 every 4 days according to bone marrow tolerance. A continuation phase was subsequently started, with alternating courses of thioguanine (6-TG) 300 mg/m2/d for 4 days plus CTX 1.2 g/m2 on day 5; hydroxyurea 2.5 g/m2/d for 4 days plus DAUNO 45 mg/m2 on day 5; VCR 1.5 mg/m2 plus methotrexate (MTX) 120 mg/m2 (24 hours apart); mercaptopurine (6-MP) 500 mg/m2/d for 4 days plus MTX 40 mg/m2; and VM-26 plus ARA-C for 3 courses (4 days apart), by the end of 48 weeks. CNS prophylaxis consisted of intrathecal administration of MTX, ARA-C, and dexamethasone according to age, administered three times during remission induction and every 6 weeks afterwards.. By the end of the analysis in July 1991, 38 of 39 patients had attained a complete remission and 36 were event-free survivors. Two failures that occurred after completion of therapy were second malignancies (acute lymphocytic leukemia and acute nonlymphocytic leukemia).. These results are significantly better than those obtained with less intensive former regimens performed in our institution before the availability of VM-26. The favorable impact of an intense consolidation phase with VM-26 is remarkably exemplified by three additional patients not included in this study whose families withdrew them from therapy after the intensification phase, all three of whom have been in remission.

Topics: Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Female; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Prednisone; Recurrence; Remission Induction; Survival Rate; Teniposide; Thioguanine; Vincristine

We report patients who were treated for non-Hodgkin's lymphoma (NHL) or Ki-1 antigen-positive (Ki-1) lymphoma with a T-8801 protocol that included etoposide (VP-16) and behenoylcytosine arabinoside.. Secondary acute myeloid leukemia (AML) developed in 5 of 38 NHL and Ki-1 lymphoma patients, and the cumulative risk at 4 years was 18.4%. The median time from the initiation of the chemotherapy to the development of AML was 21 months (range, 13-30). Four patients had a FAB M5 morphology, and one had FAB M2. In four of five examined cases, chromosomal alterations involving the long arm of chromosome 11 were demonstrated at the time of development of AML. None of the 46 NHL patients who we treated with another protocol (B-8801), using significantly higher cumulative doses of VP-16 than in the case of the patients with T-8801 and a different schedule of VP-16 administration, developed secondary AML.. The risk of secondary AML possibly related to the use of VP-16 given twice weekly.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparagine; Child; Child, Preschool; Chromosome Aberrations; Chromosomes, Human, Pair 11; Cyclophosphamide; Cytarabine; Doxorubicin; Etoposide; Female; Follow-Up Studies; Humans; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Life Tables; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Neoplasms, Second Primary; Risk; Vincristine

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Administration Schedule; Female; Humans; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Nimustine; Prednisone; Remission Induction; Vincristine

The number of circulating hematopoietic progenitor cells was determined during 47 courses of chemotherapy in 23 patients with hematopoietic malignancies. rhG-CSF was given subcutaneously to 14 patients to rescue chemotherapy-induced neutropenia following 22 courses of chemotherapy. The mean numbers of CFU-GM in patients with malignant lymphoma (ML), acute leukemia (AL) and myeloma (MM) were 56.0 +/- 58.8 (mean +/- SD), 46.7 +/- 66.0 and 11.0 +/- 11.1 CFU-GM/ml, respectively. The number of CFU-GM in MM was significantly less than in normal subjects (51.2 +/- 30.6 CFU-GM/ml). The number of CFU-GM in PB in all patients began to rise between 2 days before and 8 days after nadir of WBC count, and then reached the peak at the subsequent 5 days. The peak values of CFU-GM in ML, AL and MM were 711.3 +/- 974.7, 660.0 +/- 374.7 and 403.6 +/- 232.5 CFU-GM/ml, respectively, but there was no statistical difference among them. When ML patients were treated with rhG-CSF, the CFU-GM peak values increased as much as 5.5-folds compared with those following chemotherapy only. However, neither the period from nadir to start of increase in the CFU-GM count nor the time of the CFU-GM peak showed any significant change. These results indicate that the administration of rhG-CSF makes it possible to increase the number of circulating progenitor cells. It appears possible in most of the patients with hematopoietic malignancies to harvest the sufficient number of progenitor cells which are necessary for autologous blood stem cell transplantation.

Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cell Cycle; Colony-Stimulating Factors; Cyclophosphamide; Cytarabine; Daunorubicin; Doxorubicin; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cells; Humans; Leukemia; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Middle Aged; Multiple Myeloma; Prednisolone; Prednisone; Vincristine

The effects of some environmental and genetic factors on the inter- and intraindividual variations of 6-mercaptopurine (6-MP) pharmacokinetics were studied in children on oral remission maintenance therapy for acute lymphoblastic leukemia or non-Hodgkin's lymphoma. Blood samples were obtained 0-4 h after drug intake. 6-MP concentrations were determined in plasma and in erythrocyte concentrates. The influence of food on the pharmacokinetics was examined in a prospective study of 15 children. Each child was examined four times, twice in the fasted state and twice after intake of a standardized, milky, breakfast. There were pronounced inter- and intraindividual variations. Food intake seemed to reduce these variations but there were no significant changes in peak concentrations and area under the plasma concentration vs time curves (AUC) between the fasted and fed states. Food intake reduced the time to peak concentration both in plasma, from 1.8 h to 1.1 h (P less than 0.01) and in red blood cells, from 1.8 h to 1.3 h (P less than 0.01). Retrospective subdivision of the patients indicated a tendency for different pharmacokinetic patterns according to dose; five out of seven patients receiving greater than 70 mg m-2 had a higher AUC in the fasting state, while five out of eight patients receiving less than 70 mg m-2 had a higher AUC in the fed state. The cytochrome P-450-dependent hydroxylation capacity was evaluated with debrisoquine but no correlation was found to the pharmacokinetics of 6-MP.

Topics: Administration, Oral; Adolescent; Child; Child, Preschool; Debrisoquin; Erythrocytes; Fasting; Female; Humans; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Twenty-one children with non-Hodgkin's lymphoma (NHL) entered intensive chemotherapy study according to the protocol 6481. Sixteen patients with extraabdominal involvement achieved long-lasting remission, 15 of them have been disease-free for 17 till 77 months. Five children suffered from intraabdominal NHL, 4 of them expired because of progression of the disease within 4 months after diagnosis, 1 patient has been disease-free for 43 months. Actuarial disease-free survival is 0.76 for the whole group, 0.8 for those with extraabdominal involvement and 0.20 for children with intraabdominal forms of non-Hodgkin's lymphoma. Protocol 6481 is highly effective for extraabdominal forms of childhood non-Hodgkin's lymphomas but insufficient for abdominal forms.

Topics: Abdominal Neoplasms; Actuarial Analysis; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Bleomycin; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Doxorubicin; Female; Humans; Hydrocortisone; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Three cases of secondary leukemia developing after chemotherapy and/or radiotherapy for myeloma, mycosis fungoides, and non-Hodgkin's lymphoma are reported. The first case was a 51-year-old man with IgG-lambda myeloma, treated with melphalan and prednisolone, who developed acute myelomonocytic leukemia 54 months after the diagnosis of myeloma. The second case was a 54-year-old woman with mycosis fungoides treated with radiation, predonine, and cyclophosphamide, who developed acute megakaryoblastic leukemia 298 months after the diagnosis of mycosis fungoides. The third case was a 35-year-old woman with stage IV non-Hodgkin's lymphoma treated with VEMP who developed acute myelogenous leukemia 26 months after the diagnosis of malignant lymphoma. All cases showed pancytopenia and two of three cases had morphologic abnormality in several hemopoietic cell lineages in the leukemic stage. There is a possibility that second malignancies are an increasingly recognized complication in the patients treated with a large amount of chemo-radiotherapy.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Female; Humans; Leukemia; Leukemia, Megakaryoblastic, Acute; Leukemia, Myeloid, Acute; Leukemia, Radiation-Induced; Lymphoma, Non-Hodgkin; Male; Melphalan; Mercaptopurine; Middle Aged; Multiple Myeloma; Mycosis Fungoides; Pancytopenia; Prednisolone; Vincristine

Plasma and erythrocyte concentrations of 6-mercaptopurine (6-MP) were determined by gas chromatography-mass spectrometry. Eleven children (9 with acute lymphatic leukemia) were studied after oral intake of 6-MP doses ranging between 31 and 128 mg/m2 body surface area. The concentrations of 6-MP in plasma were found to vary considerably between patients even after dose normalization to 75 mg/m2. After dose normalization the mean peak plasma concentration was 0.68 microM (range 0.12-1.38) and the area under the plasma concentration-time curve (AUC) was 1.37 microM.h (range 0.12-3.04). The mean time taken to reach the peak concentration was 1.3 h (range 1-2), and the half-life of elimination was 1.8 h (range 0.6-2.5). No patient had detectable 6-MP concentrations 12 h after dose intake. The concentrations of 6-MP tended to be higher in erythrocytes than in plasma. The mean peak concentration in erythrocytes was 131% and the AUC 145% of that found in plasma. The mean half-life of elimination from erythrocytes was 2.0 h (range 0.7-2.8). These data indicate that 6-MP can pass through all membranes rapidly to reach intracellular concentrations equal to or even higher than in plasma. In summary, marked interindividual differences in pharmacokinetics were found, probably due to highly variable bioavailability of oral 6-MP. Further studies are needed to determine whether measurements of plasma concentrations of 6-MP can be used to optimize maintenance treatment of childhood leukemia.

Topics: Administration, Oral; Adolescent; Autoimmune Diseases; Child; Child, Preschool; Drug Evaluation; Erythrocytes; Female; Humans; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Pilot Projects; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Fourteen children with mediastinal lymphoblastic lymphoma (MLL) were treated with the six-drug APO protocol. This regimen includes aggressive intermittent chemotherapy and prophylactic central nervous system therapy. Mediastinal irradiation was given only for emergency relief of mediastinal compression (two children) or for incomplete resolution of mediastinal widening with chemotherapy (one child). All 14 patients achieved complete remission; only 1 has relapsed. Toxicities were not severe. APO is effective therapy for children with MLL. APO should receive further trials in children and adults with T-cell lymphoblastic lymphomas.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Child, Preschool; Doxorubicin; Female; Humans; Lymphoma, Non-Hodgkin; Male; Mediastinal Neoplasms; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Azathioprine; Colitis; Female; Humans; Lymphoma, Non-Hodgkin; Mercaptopurine; Middle Aged

Thirteen adult patients with histologically confirmed lymphoblastic lymphoma were treated with an intensive chemotherapy program consisting of induction with cyclophosphamide, adriamycin, vincristine, and prednisone (modified CHOP); consolidation and central nervous system (CNS) prophylaxis with methotrexate intrathecally and by high-dose intravenous injection, citrovorum factor and L-asparaginase; reinforcement with CHOP; and maintenance with 6-mercaptopurine and methotrexate. Treatment duration was 1 yr. A 14th patient with T-cell acute lymphoblastic leukemia was also treated at presentation by the same regimen. Thirteen patients had at least a mediastinal mass or abnormal cells in the bone marrow; one presented with CNS disease. The median age was 22 yr (range 16--50), and male--female ratio was 2.5:1. All patients had a rapid complete clinical response. Of the 13 patients without initial CNS disease, 4 have relapsed, 3 with primary CNS relapse and 1 with a recurrent abdominal mass. Five patients have died, 2 from drug toxicity, 2 from CNS relapse, and 1 from chronic myelogenous leukemia, which was diagnosed simultaneously with the lymphoblastic lymphoma. The median follow-up is 19 mo, and all patients have completed their planned therapy. At 3 yr, the actuarial survival is 61% and relapse-free survival is 56%.

Topics: Adolescent; Adult; Asparaginase; Central Nervous System Diseases; Cyclophosphamide; Doxorubicin; Female; Humans; Leucovorin; Leukemia, Myeloid; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Vincristine

Topics: Adolescent; Anaphylaxis; Asparaginase; Child; Child, Preschool; Confusion; Daunorubicin; Female; Hallucinations; Hemorrhage; Humans; Injections, Spinal; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Mercaptopurine; Methotrexate; Pancreatitis; Prednisolone; Retroperitoneal Space; Vinblastine; Vincristine

Reticulosarcoma-like skin lesions are described in a boy with phenylketonuria (PKU) who was observed for 11 years. Association of the lesions with PKU is indicated by their dependence on the severity of the latter and their complete healing during treatment with low phenylalanine diet.

Topics: Biopsy; Child; Child, Preschool; Humans; Infant; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Phenylketonurias; Prednisolone; Skin; Skin Manifestations; Skin Neoplasms

Topics: Age Factors; Antineoplastic Agents; Asparaginase; Child; Cyclophosphamide; Cytarabine; Daunorubicin; Evaluation Studies as Topic; Humans; Injections, Intravenous; Injections, Spinal; Lymphoma, Non-Hodgkin; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Vincristine

Topics: Adolescent; Adult; Aged; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Middle Aged; Moscow; Prednisolone; Remission, Spontaneous; Time Factors; Vincristine

Topics: Animals; Antineoplastic Agents; Cattle; Cells, Cultured; Cytidine; Cytosine Nucleotides; Drug Resistance; Fluorouracil; Leukemia L1210; Leukemia, Experimental; Lymphoma, Non-Hodgkin; Mercaptopurine; Mice; Mice, Inbred Strains; Oxidative Phosphorylation; Pentosephosphates; Pentosyltransferases; Phosphotransferases

Topics: Adenosine Triphosphate; Animals; Bone Marrow; Carcinoma, Hepatocellular; Cattle; Cell Line; Cell-Free System; Chromatography, DEAE-Cellulose; Cytarabine; Cytidine; Deoxyribonucleosides; Dithiothreitol; Guanosine; Humans; Isoenzymes; Kinetics; Leukemia L1210; Liver Neoplasms; Lymphoma, Non-Hodgkin; Magnesium; Mercaptopurine; Mice; Mice, Inbred AKR; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred DBA; Phosphotransferases

Topics: Adenine Nucleotides; Adult; Animals; Antibiotics, Antineoplastic; Arabinose; Carcinoma, Squamous Cell; Cricetinae; Dogs; Humans; Hypoxanthines; Kidney; Leukemia, Lymphoid; Lung Neoplasms; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Mice; Middle Aged; Neoplasms; Nucleosides; Nucleotidases; Nucleotides; Phosphorus; Rabbits; Sulfur Isotopes; Time Factors; Tritium

Topics: Adult; Age Factors; Benzoates; Blood Cell Count; Blood Platelets; Cyclophosphamide; Drug Combinations; Female; Hodgkin Disease; Humans; Lymphoma; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Middle Aged; Prednisone; Procarbazine; Time Factors; Vincristine

Topics: Bone Marrow; Bone Marrow Cells; Bone Marrow Examination; Chromosome Aberrations; Culture Techniques; Cyclophosphamide; Cytarabine; Female; Humans; Karyotyping; Lectins; Lymph Nodes; Lymphoma, Non-Hodgkin; Mercaptopurine; Middle Aged; Prednisolone; Trisomy; Vincristine

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Asparaginase; Azaserine; Cyclophosphamide; Cytarabine; Daunorubicin; Female; Fluorouracil; Hydrocarbons, Halogenated; Lymphoma, Non-Hodgkin; Mercaptopurine; Mice; Mice, Inbred Strains; Neoplasm Transplantation; Prednisolone; Remission, Spontaneous; Sarcoma, Experimental; Thiotepa; Time Factors; Triethylenemelamine; Vinblastine; Vincristine

Topics: Animals; Drug Synergism; Lymphoma, Non-Hodgkin; Mercaptopurine; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Sarcoma 180; Uracil

Topics: Adolescent; Child; Child, Preschool; Cobalt Isotopes; Cyclophosphamide; Head and Neck Neoplasms; Humans; Leukemia; Lymphoma, Non-Hodgkin; Mediastinal Neoplasms; Mercaptopurine; Methotrexate; Peritoneal Neoplasms; Prednisone; Radioisotope Teletherapy; Remission, Spontaneous; Time Factors; Vincristine

Topics: Adolescent; Adult; Aged; Asparaginase; Azaserine; Burkitt Lymphoma; Central Nervous System Diseases; Chemical and Drug Induced Liver Injury; Child; Drug Hypersensitivity; Escherichia coli; Female; Humans; Leukemia, Lymphoid; Leukopenia; Lymphoma, Non-Hodgkin; Lymphopenia; Male; Mercaptopurine; Methotrexate; Middle Aged; Neoplasms; Pancreatitis; Thrombocytopenia

Topics: Antineoplastic Agents; Busulfan; Carcinoma, Squamous Cell; Child; Chlorambucil; Choriocarcinoma; Dactinomycin; Female; Fluorouracil; Gonadal Steroid Hormones; Hodgkin Disease; Humans; Hydrazines; Leukemia; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Mesenchymoma; Methotrexate; Multiple Myeloma; Nitrogen Mustard Compounds; Ovarian Neoplasms; Pregnancy; Prostatic Neoplasms; Steroids; Testicular Neoplasms; Urethane; Vinblastine; Vincristine; Wilms Tumor

Topics: Adult; Aged; Anti-Bacterial Agents; Antineoplastic Agents; Child; Female; Humans; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisolone

Topics: Cyclophosphamide; Humans; Leukemia; Lymphoma, Non-Hodgkin; Mercaptopurine; Methotrexate

Topics: Adolescent; Child; Child, Preschool; Cyclophosphamide; Dactinomycin; Female; Humans; Infant; Leukemia; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Neoplasm Metastasis; Paraplegia; Prednisolone; Retroperitoneal Neoplasms; Sarcoma, Ewing; Spinal Cord Neoplasms; Vinblastine; Vincristine; Wilms Tumor

Topics: Antibiotics, Antineoplastic; Child; Humans; Lymphoma, Non-Hodgkin; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Busulfan; Drug Synergism; Lymphoma, Non-Hodgkin; Melphalan; Mercaptopurine; Mice; Neoplasms, Experimental; Nitrogen Mustard Compounds; Oligomycins; Thiotepa; Uracil Mustard

Topics: Adolescent; Bone Marrow Examination; Child; Child, Preschool; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Mercaptopurine; Methotrexate; Prednisone

Topics: Blood Cell Count; Cytarabine; DNA; Humans; In Vitro Techniques; Injections, Intravenous; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Mercaptopurine; Multiple Myeloma; Prednisone; RNA; Tritium; Uridine; Vincristine

Topics: Antineoplastic Agents; Busulfan; Cyclophosphamide; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Agammaglobulinemia; Aged; Animals; Autoimmune Diseases; Body Weight; Female; Globulins; Guinea Pigs; Humans; Immunosuppressive Agents; Lymphoma, Non-Hodgkin; Mercaptopurine; Methotrexate; Prednisone; Skin Tests; Smallpox Vaccine; Travel

Topics: Alkylating Agents; Aminopterin; Busulfan; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mechlorethamine; Mercaptopurine; Methotrexate; Multiple Myeloma; Neoplasms; Pathology; Primary Myelofibrosis; Sarcoma; Triethylenemelamine; Tuberculosis; Tuberculosis, Pulmonary; Urethane

Topics: Animals; Estradiol; Friends; Leukemia; Leukemia Virus, Murine; Leukemia, Experimental; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mercaptopurine; Methylcellulose; Mice; Mitomycin; Mitomycins; Neoplasm Transplantation; Neoplasms; Pharmacology; Research; Sarcoma; Triethylenemelamine; Urethane

Topics: Adrenal Cortex Hormones; Chlorambucil; Cyclophosphamide; Dermatitis, Exfoliative; Genetic Diseases, X-Linked; Geriatrics; Hodgkin Disease; Leukemia; Leukemia, Hairy Cell; Leukemia, Lymphoid; Lymphatic Diseases; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mercaptopurine; Methotrexate; Mycosis Fungoides; Neoplasms; Pathology; Peptide Nucleic Acids; Physiology; Sarcoma; Severe Combined Immunodeficiency

Topics: Anemia; Anemia, Hemolytic; Betamethasone; Chlorambucil; Dexamethasone; Geriatrics; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Lymphoma, Non-Hodgkin; Mechlorethamine; Mercaptopurine; Methylprednisolone; Pharmacology; Prednisone; Radiotherapy; Thrombocytopenia; Triamcinolone

Topics: Adolescent; Black People; Child; Chlorambucil; Cyclophosphamide; Dactinomycin; Geriatrics; Leukemia; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mechlorethamine; Mercaptopurine; Neoplasms; Phagocytosis; Sarcoma; Steroids; Triethylenemelamine

Topics: Chlorambucil; Hematopoiesis; Hodgkin Disease; Humans; Lymphoma; Lymphoma, Non-Hodgkin; Mercaptopurine; Neoplasms; Paraplegia; Prednisone; Spinal Cord Compression

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Busulfan; Carcinoma, Ehrlich Tumor; Leukemia; Leukemia, Myeloid; Lymphoma; Lymphoma, Non-Hodgkin; Mercaptopurine; Mice; Neoplasms, Experimental; Nitrogen Mustard Compounds; Olivomycins; Pharmacology; Research; Sarcoma 180; Thiotepa; Toxicology

Topics: Antineoplastic Agents; Busulfan; Child; Cyclophosphamide; Dactinomycin; Humans; Hydroxyurea; Leukemia; Leukemia, Lymphoid; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mercaptopurine; Neoplasms; Neuroblastoma; Sarcoma; Urea

Topics: Adrenal Cortex Hormones; Busulfan; Chlorambucil; Cortisone; Cyclophosphamide; Hodgkin Disease; Humans; Leukemia; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mechlorethamine; Mercaptopurine; Methotrexate; Neoplasms; Palliative Care; Sarcoma; Vinblastine

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Glutaminase; Leukemia; Leukemia, Experimental; Lymphoma; Lymphoma, Non-Hodgkin; Mercaptopurine; Mice; Neoplasms; Neoplasms, Experimental; Pharmacology; Research; Sarcoma 180; Toxicology

Topics: Adolescent; Alkylating Agents; Antimetabolites; Antineoplastic Agents; Blood Cell Count; Female; Glucocorticoids; Humans; Leukemia; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mercaptopurine; Multiple Myeloma; Polycythemia Vera

Topics: Cause of Death; Child; Death, Sudden; Folic Acid; Humans; Intussusception; Leukemia; Leukemia, Lymphoid; Lymphocytes; Lymphoma, Non-Hodgkin; Mercaptopurine; Steroids

Topics: Busulfan; Hodgkin Disease; Inflammation; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukocyte Count; Lymphoma; Lymphoma, Non-Hodgkin; Mercaptopurine; Nitrogen Mustard Compounds; Skin Tests; Skin Window Technique

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antitubercular; Antineoplastic Agents; Busulfan; Cytostatic Agents; Lymphoma; Lymphoma, Non-Hodgkin; Mercaptopurine; Methylthiouracil; Mice; Neoplasms, Experimental; Nitrogen Mustard Compounds; Olivomycins; Pharmacology; Research; Thiotepa

Topics: Alkylating Agents; Animals; Antineoplastic Agents; Azaguanine; Azaserine; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; DNA; DNA, Neoplasm; Fluorouracil; Idoxuridine; Liver Neoplasms; Lymphoma; Lymphoma, Non-Hodgkin; Mercaptopurine; Mice; Neoplasms, Experimental; Nitrogen Mustard Compounds; Nucleosides; Nucleotides; Purines; Research; RNA; RNA, Neoplasm; Sarcoma 180; Thioguanine; Uracil Mustard

Topics: Adrenal Cortex Hormones; Aged; Bone Marrow; Busulfan; Chlorambucil; Cyclophosphamide; Hodgkin Disease; Humans; Leukemia; Lymphoid Tissue; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mercaptopurine; Methotrexate; Multiple Myeloma; Neoplasms; Sarcoma

Topics: Blood; Cytodiagnosis; Hodgkin Disease; Humans; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mercaptopurine; Neoplasms; Sarcoma; Vinblastine

Topics: Humans; Leukemia; Lymphoma; Lymphoma, Non-Hodgkin; Mercaptopurine; Purines