mercaptopurine and Burkitt-Lymphoma

Although cytotoxic immunosuppressive agents play an unquestionably useful role in treating many neoplastic and non-neoplastic disorders, there is accumulating evidence that the toxicity associated with their use is considerable. The therapeutic successes obtained with antitumor agents have led to increases in the life span of cancer patients, but have also provided the opportunity for this toxicity to become manifest. A search of the available literature was carried out, with emphasis on cases in which a malignancy developed in patients following chemotherapy for either neoplastic or non-neoplastic (e.g., renal transplantation, psoriasis) conditions; particular focus was given to the incidence of acute myelogenous leukemia in various groups of Hodgkin's disease and multiple myeloma patients. That patients with nonmalignant conditions treated with cytotoxic immunosuppressive agents are also at increased risk of developing a malignancy raises the possibility that these agents may have oncogenic potential. Therefore, one may be faced with the paradox that the patients benefiting most from chemotherapy may be at highest risk of suffering its consequences.

Topics: Alkylating Agents; Animals; Antineoplastic Agents; Azathioprine; Burkitt Lymphoma; Choriocarcinoma; Cyclophosphamide; Dactinomycin; Female; Hodgkin Disease; Humans; Immunosuppressive Agents; Kidney Neoplasms; Leukemia, Myeloid, Acute; Lymphoma; Mechlorethamine; Melphalan; Mercaptopurine; Methotrexate; Mice; Multiple Myeloma; Neoplasms; Prednisone; Pregnancy; Procarbazine; Time Factors; Vincristine

Topics: Adult; Burkitt Lymphoma; Child; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Combinations; Hodgkin Disease; Humans; Immunotherapy; Infections; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma; Mercaptopurine; Methotrexate; Middle Aged; Nitrogen Mustard Compounds; Prednisone; Procarbazine; Prognosis; Remission, Spontaneous; Vincristine

Topics: Acute Disease; Administration, Oral; Adult; Age Factors; Body Weight; Burkitt Lymphoma; Carcinoma, Squamous Cell; Child; Choriocarcinoma; Drug Combinations; Female; Folic Acid Antagonists; Humans; Injections, Intramuscular; Injections, Intravenous; Leukemia; Mercaptopurine; Methotrexate; Prednisone; Pregnancy; Time Factors; Vincristine

Topics: Acute Disease; Animals; Asparaginase; Burkitt Lymphoma; Child; Cyclophosphamide; Cytarabine; Dactinomycin; Daunorubicin; Fluorouracil; Humans; Leukemia; Melphalan; Mercaptopurine; Methotrexate; Mice; Oncogenic Viruses; Prednisolone; Prednisone; Vincristine

Methotrexate (MTX) and mercaptopurine (MP) are widely used antileukemic agents that inhibit de novo purine synthesis (DNPS) as a mechanism of their antileukemic effects. To elucidate pharmacodynamic differences among children with acute lymphoblastic leukemia (ALL), DNPS was measured in leukemic blasts from newly diagnosed patients before and after therapy with these agents. Patients were randomized to receive low-dose MTX (LDMTX: 6 oral doses of 30 mg/m(2)) or high-dose MTX (HDMTX: intravenous 1 g/m(2)) followed by intravenous MP; or intravenous MP alone (1 g/m(2)), as initial therapy. At diagnosis, the rate of DNPS in bone marrow leukemia cells was 3-fold higher in patients with T-lineage ALL compared with those with B-lineage ALL (769 +/- 189 vs 250 +/- 38 fmol/nmol/h; P =.001). DNPS was not consistently inhibited following MP alone but was markedly inhibited following MTX plus MP (median decrease 3% vs 94%; P <.001). LDMTX plus MP and HDMTX plus MP produced greater antileukemic effects (percentage decrease in circulating leukocyte counts) compared with MP alone (-50% +/- 4%, -56% +/- 3%, and - 20% +/- 4%, respectively; P <.0001). Full DNPS inhibition was associated with greater antileukemic effects compared with partial or no inhibition (-63% +/- 4% vs -37% +/- 4%; P <.0001) in patients with nonhyperdiploid B-lineage and T-lineage ALL. HDMTX plus MP yielded 2-fold higher MTX polyglutamate concentrations than LDMTX plus MP (2148 +/- 298 vs 1075 +/- 114 pmol/10(9) cells; P <.01) and a higher percentage of patients with full DNPS inhibition (78% vs 53%; P <.001). Thus, the extent of DNPS inhibition was related to in vivo antileukemic effects, and a single dose of intravenous MP produced minimal DNPS inhibition and antileukemic effects, whereas MTX plus MP produced greater antileukemic effects and DNPS inhibition, with full inhibition more frequent after HDMTX.

Topics: Adolescent; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Cells; Burkitt Lymphoma; Child; Child, Preschool; Female; Humans; Infant; Leukemia-Lymphoma, Adult T-Cell; Leukocyte Count; Male; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Purines

We postulated that intensification of chemotherapy immediately after remission induction might reduce the leukemic cell burden sufficiently to allow an abbreviated period of antimetabolite therapy.. Three hundred forty-seven children (ages 1 to 15 years) with previously untreated acute lymphoblastic leukemia (ALL) were enrolled onto the Tokyo L92-13 study, which excluded patients with mature B-cell ALL and patients less than 1 year old. One hundred twenty-four patients were classified as standard risk, 122 as high risk, and 101 as extremely high risk, according to age, peripheral-blood leukocyte count, selected genetic abnormalities, and immunophenotype. All subjects received four drugs for remission induction, followed by a risk-directed multidrug intensification phase and therapy for presymptomatic leukemia in the CNS. Maintenance chemotherapy with oral mercaptopurine and methotrexate was administered for 6 months, with all treatment stopped by 1 year after diagnosis.. The mean (+/- SD) event-free survival (EFS) and overall survival rates for all patients were 59.5% +/- 3.4% and 81.5% +/- 2.2%, respectively, at 5. 5 years after diagnosis. EFS rates by risk category were similar (60. 2% +/- 6.0% for standard risk, 57.7% +/- 5.6% for high risk, and 62. 5% +/- 5.7% for extremely high risk), whereas overall survival rates differed significantly (91.2% +/- 2.7%, 80.0% +/- 4.1%, and 72.1% +/- 4.5%, respectively, P <.0001 by the log-rank test). There were 107 relapses. Eighty-five (79.4%) of these 107 patients achieved second complete remissions, with subsequent EFS rates of 61.5% +/- 7. 9% (standard risk), 42.6% +/- 8.1% (high risk), and 9.6% +/- 6.4% (extremely high risk). Of the five risk factors analyzed, only the response to prednisolone monotherapy among extremely high-risk patients proved important.. Early treatment intensification did not compensate for a truncated phase of maintenance chemotherapy in children with standard- or high-risk ALL. However, 6 months of antimetabolite treatment seemed adequate for extremely high-risk patients who were good responders to prednisolone and received intensified chemotherapy that included high-dose cytarabine early in the clinical course.

Topics: Adolescent; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Child; Child, Preschool; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Infant; Male; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Risk Factors; Treatment Outcome

To determine whether early intensification with 12 courses of intravenous methotrexate and intravenous mercaptopurine (IVMTX/IVMP) is superior to 12 courses of repetitive, low-dose oral MTX with I.V. MP (LDMTX/IVMP) for prevention of relapse in children with lower-risk B-lineage acute lymphoblastic leukemia (ALL).. Seven hundred nine patients were entered onto the study. Vincristine, prednisone, and asparaginase were used for remission induction. Patients were randomized to receive intensification with either IVMTX 1,000 mg/m2 plus IVMP 1,000 mg/m2 (regimen A) or LDMTX 30 mg/m2 every 6 hours for six doses with IVMP 1,000 mg/m2 (regimen B). Twelve courses were administered at 2-week intervals. Triple intrathecal therapy (TIT) was used for CNS prophylaxis. Continuation therapy included standard oral MP, weekly MTX, and TIT every 12 weeks for 2 years.. Six hundred ninety-nine (99%) patients achieved remission. Three hundred forty-nine were assigned to regimen A and 350 to regimen B. The estimated 4-year continuous complete remission (CCR) rate for patients treated with regimen A is 80.3% (SE = 2.9%) and with regimen B is 75.9% (SE = 3.1%). By log-rank analysis, regimen A demonstrated superior CCR (P = .013). Transient neutropenia/thrombocytopenia, bacterial sepsis, neurotoxicity, stomatitis, and hospitalizations were more frequent among patients treated on regimen A.. Intensification with IVMTX/IVMP is more effective than LDMTX/IVMP for prevention of relapse in children with B-precursor ALL at lower risk for relapse.

Topics: Administration, Oral; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Child, Preschool; Female; Humans; Infusions, Intravenous; Leucovorin; Male; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Proportional Hazards Models; Remission Induction; Sex Factors; Treatment Failure

TEL gene rearrangement is the most common genetic lesion in pediatric acute lymphoblastic leukemia (ALL), occurring in about 25% of B-lineage cases. We previously showed that, among patients treated on St Jude protocols, TEL rearrangement independently conferred an excellent prognosis. To extend these results to patients treated with antimetabolite-based therapy, we performed Southern blot analysis to determine the TEL gene status of 104 cases of B-lineage ALL treated on Pediatric Oncology Group 8602, matched on age, gender, and leukocyte count. There were 52 failures among the 77 patients with germline TEL, compared with only 8 failures among 27 patients in the rearranged group. Based on a two-sided logistic regression analysis, stratified for age (subdivided at 10 years), leukocyte count (subdivided at 50,000), and gender, the estimated odds of failing by 4 years in the germline TEL group is 5.4 times that of the rearranged TEL group, with 95% confidence from 1.9 to 15.6, two-sided P = .0009. Thus, the presence of a rearranged TEL gene is also associated with an improved survival among patients treated with antimetabolite-based therapy. Our results indicate that all newly diagnosed ALL patients should be screened for TEL gene rearrangements and suggest that these patients are candidates for less intensive therapy.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Biomarkers, Tumor; Blotting, Southern; Burkitt Lymphoma; Case-Control Studies; Child; Chromosomes, Human, Pair 12; Chromosomes, Human, Pair 21; Core Binding Factor Alpha 2 Subunit; Cytarabine; DNA, Neoplasm; Female; Humans; Hydrocortisone; Male; Mercaptopurine; Methotrexate; Neoplasm Proteins; Oncogene Proteins, Fusion; Prednisone; Prognosis; Remission Induction; Retrospective Studies; Single-Blind Method; Translocation, Genetic; Treatment Outcome; Vincristine

A total of 119 children (1990-95) with acute lymphoblastic leukemia (ALL) B-lineage either CD10+ or CD10- were registered into a single non-randomized chemotherapy protocol. Only untreated patients with standard risk were included in the study. Their ages ranged from 1.8-10 years with a mean of 5.1 years. There were 82 (68%) children with early pre B-All, 35 (29%) with pre B-ALL and 2(1.6%) with transitional pre B-ALL (p < 0.00001). The patients were divided according to CD10 reactivity, either + (94 children) or -(25 patients). The event-free survival (EFS) at 60 months for the CD10+ children was of 78% (alive 73/94), while for the CD10- was 71% (alive 18/25) (p = 0.6) and 74% for both groups. The factors that influenced favorably the survival in the CD10+ group were the age between 3 to 5.99 years (p < 0.00001), sex (either male or female), leukocyte count between 10-24.9 x 10(9)/l (p < 0.00001), LDH under 300 U/I (p < 0.00001) and L1 bone marrow cytomorphology (p < 0.00001). In the CD10- patients, the EFS was favorably influenced by the female sex (p = 0.04), leukocyte count under 10 x 10(9)/l (p = 0.05) and LDH < 300 U/l (p = 0.02). CNS infiltration was documented in 4.2% (5/119). Mortality secondary to chemotherapy was seen in 7%. In conclusion, this is the first large series in Mexican children with B-lineage ALL published. Because of the relatively small number of patients in each group (pre B and transitional pre B), all the patients in the current series were treated alike. When the 119 patients were divided only on the basis of CD10 reactivity, the EFS for both groups (CD10+ and-) was similar; therefore, the reactivity to CD10 has no prognostic value in this type of ALL.

Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Burkitt Lymphoma; Child; Child, Preschool; Cytarabine; Disease-Free Survival; Female; Humans; Immunophenotyping; Infant; Life Tables; Male; Mercaptopurine; Methotrexate; Neprilysin; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Prognosis; Risk Factors; Survival Analysis; Teniposide; Treatment Outcome; Vincristine

From February 1986 to January 1991 the Pediatric Oncology Group (POG) treated 2404 children or adolescents with acute lymphoblastic leukemia (ALL) on immunophenotype (T-, B-, Pre-B, or Early pre-B-cell), age, and leukocyte count based treatment protocols (ALinC 14, T-cell 3, B-cell and infant leukemia studies). The immunophenotypic subgroups comprised 78.9% B-precursor cell, 15.1% T-cell, 2.0% B-cell, and 4% infant ALL. Patients with B-progenitor cell ALL were stratified by age and leukocyte count and randomized to receive induction therapy comprised of vincristine, prednisone, and asparaginase with triple intrathecal chemotherapy (methotrexate, hydrocortisone, cytarabine), followed by intensification with moderate-dose MTX (Regimen A), moderate-dose MTX plus asparaginase (Regimen B), moderate-dose MTX plus cytarabine given early (Regimen C), or moderate-dose MTX plus cytarabine given over the first 16 months of therapy (Regimen D). Continuation therapy comprised mercaptopurine and methotrexate with vincristine plus prednisone pulses. Central nervous system preventive treatment was continued for two years. Patients with T-cell or B-cell ALL or infants less than 1 yr old were treated on individual very intensive multiagent therapy protocols. The 4-year event-free survival for all patients was 66.4% +/- 2.4%; B-precursor ALL approximately 72%, T-ALL approximately 50%, B-ALL approximately 60%, and infants less than 1 yr old approximately 16.5%. We conclude that about two-thirds of newly diagnosed children with ALL can be cured with this approach which spares the majority of children exposure to alkylating agents, anthracyclines, epipodophylotoxins, and irradiation, diminishing the risks of serious acute and late effects.

Topics: Adolescent; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Burkitt Lymphoma; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Flow Cytometry; Humans; Hydrocortisone; Immunophenotyping; Infant; Infant, Newborn; Leukemia-Lymphoma, Adult T-Cell; Mercaptopurine; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Prognosis; Remission Induction; Vincristine

6-mercaptopurine is a mainstay of acute lymphoblastic leukemia treatment. It has a narrow therapeutic window, dictated by its metabolite, thioguanine and 6-methylmercaptopurine. Skin manifestations usually consist of mild facial rash or hypersensitivity exanthems. We report a child who developed a painful acral rash and mucositis while undergoing maintenance therapy for B-cell acute lymphoblastic leukemia without infectious or known drug etiology. Thiopurine metabolites were skewed toward 6-methylmercaptopurine. Two weeks after allopurinol was added and 6-mercaptopurine (6-MP) dose adjusted, the cutaneous manifestations and other constitutional symptoms resolved. We posit that the rash was because of 6-MP toxicity related to skewed metabolism, adding to the growing list of toxicity related to altered 6-MP metabolism.

Topics: Allopurinol; Burkitt Lymphoma; Child; Exanthema; Humans; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Thioguanine

Topics: Acute Disease; Burkitt Lymphoma; Chemical and Drug Induced Liver Injury; COVID-19; COVID-19 Drug Treatment; Humans; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; SARS-CoV-2

The hyper-CVAD/methotrexate-cytarabine (H-CVAD/ MTX-AraC) chemotherapy protocol has been one of the standard treatments for hematological malignancies, such as mantle cell lymphoma (MCL), Burkitt lymphoma (BL), and B-cell and T-cell acute lymphoblastic leukemia. Because results of this therapy are poor, it has been progressively replaced with new specific regimens with better efficacy profiles (GELA protocol for MCL, BURKIMAB for BL, and PETHEMA for B-cell and T-cell acute lymphoblastic leukemia [ALL]). The objective of this study was to analyze the response rates and survival of these therapeutic regimens. This retrospective and descriptive observational study of 81 patients compared 42 patients treated with hyper-CVAD/methotrexate-cytarabine (group A) with 39 patients treated with GELA/BURKIMAB/PETHEMA (group B). More patients in group B than in group A completed the treatment (89.7% vs. 47.6%, p < 0.001). In group A, 14.3% did not complete treatment because of death compared with 7.7% in group B, and 29% in group A had cycle delays versus 6.7% in group B (p < 0.001). In group A, 78.6% of group A achieved a complete response (CR) compared with 94.9% of group B (p = 0.050). Disease-free survival (DFS) and overall survival (OS) were significantly higher in group B (p < 0.001 in both cases). Data for current therapeutic protocols have indicated superior efficacy, with higher complete response rates, as well as better disease-free survival and overall survival results. This article provides the best results in terms of the efficacy of treatment of four hematological malignancies (MCL, BL, B-cell ALL, and T-cell ALL) with the most current specific therapeutic regimens (GELA for MCL, BURKIMAB for BL, and PETHEMA for B-cell ALL and T-cell ALL) with respect to a classic general protocol (H-CVAD/MTX-AraC for all four). These results may represent a great advance in the treatment of these blood cancers, achieving an important long-term benefit for these hematological patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Burkitt Lymphoma; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Hematologic Neoplasms; Humans; Lymphoma, Mantle-Cell; Male; Mercaptopurine; Methotrexate; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Retrospective Studies; Treatment Outcome; Vincristine; Young Adult

Patients with relapsed/refractory Burkitt's lymphoma (BL) have a dismal prognosis. Current research efforts aim to increase cure rates by identifying high-risk patients in need of more intensive or novel therapy. The 8q24 chromosomal translocation of the c-Myc gene, a main molecular marker of BL, is related to the metabolism by regulating phosphoribosyl pyrophosphate synthetase 2 (PRPS2). In our study, BL showed significant resistance to thiopurines. PRPS2 homologous isoenzyme, PRPS1, was demonstrated to play the main role in thiopurine resistance. c-Myc did not have direct effects on thiopurine resistance in BL for only driving PRPS2. PRPS1 wild type (WT) showed different resistance to 6-mercaptopurine (6-mp) in different metabolic cells because it could be inhibited by adenosine diphosphate or guanosine diphosphate negative feedback. PRPS1 A190T mutant could dramatically increase thiopurine resistance in BL. The interim analysis of the Treatment Regimen for Children or Adolescent with mature B cell non-Hodgkin's lymphoma in China (CCCG-B-NHL-2015 study) confirms the value of high-dose methotrexate (MTX) and cytarabine (ARA-C) in high-risk paediatric patients with BL. However, there remains a subgroup of patients with lactate dehydrogenase higher than four times of the normal value (4N) for whom novel treatments are needed. Notably, we found that the combination of thiopurines and the phosphoribosylglycinamide formyltransferase (GART) inhibitor lometrexol could serve as a therapeutic strategy to overcome thiopurine resistance in BL.

Topics: Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Cell Line, Tumor; Drug Resistance, Neoplasm; HEK293 Cells; Humans; Mercaptopurine; Mutation; Nucleotides; Proto-Oncogene Proteins c-myc; Ribose-Phosphate Pyrophosphokinase; Tetrahydrofolates

The objective was to evaluate the feasibility and efficacy of a short-term, multi-agent and dose intensive regimen in AIDS patients with Burkitt or Burkitt-like lymphoma (BL/BLL) and to compare its efficacy with that of a conventional regimen. This was a retrospective, multi-center cohort study of all HIV-1-infected patients diagnosed with BL/BLL between 1990 - 2004. Patients were assigned to two different chemotherapy approaches. Group A received a protocol which was adapted from the German multi-center study group for adult acute lymphoblastic leukemia (GMALL). Group B received a conventional CHOP-based chemotherapy. Fifty-one patients were included in the analysis. In group A (n = 20), significantly more patients achieved complete remission (75% vs 40%, P = 0.02) than in group B (n = 31). One-year survival in group A was 65% compared to 44% in group B (P = 0.17). In a multi-variable Cox regression analysis, treatment according to the GMALL protocol was significantly associated with prolonged survival with a relative hazard rate of 0.13 (95% CI 0.03 - 0.63, P = 0.01). In conclusion, the short and intensive GMALL protocol for B-ALL/NHL is feasible in patients with AIDS-BL/BLL. Outcome may be improved compared to patients treated with CHOP-based regimens. In the era of HAART, more intensive chemotherapy regimens should be considered in patients with highly aggressive lymphomas.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; Burkitt Lymphoma; Cohort Studies; Cyclophosphamide; Cytarabine; Daunorubicin; Doxorubicin; Drug Therapy, Combination; Feasibility Studies; Female; Humans; Lymphoma, AIDS-Related; Male; Mercaptopurine; Prednisolone; Prednisone; Prognosis; Prospective Studies; Remission Induction; Retrospective Studies; Survival Rate; Treatment Outcome; Vincristine

To compare programs of chemotherapy used in adult Berkitt-like lymphoma (ABLL); to assess efficacy and toxicity of the protocol AblL-M-04.. 31 ABLL patients (23 males, 8 females, mean age 27 years) participated in the study performed in Hematological Research Center in 1995-2004. ABLL stage I, II, III and IV was diagnosed in 3, 5, 8 and 15 patients, respectively. 10 patients had diffuse large B-cell lymphoma. 9 patients received 2 to 6 courses of CHOP, 1 patient--6 courses of Pro-Mace-Cytabom, 11 patients with newly diagnosed ABLL and 5 pretreated with CHOP--NHL-BFM-90. The modified protocol ABLL-M-04 of intensive short-term therapy included 10 patients, 2 of them pretreated.. Of 10 patients given CHOP or CHOP-like courses 9 were resistant to therapy, 2 died of rapid progression, 7 were converted to the program therapy. 5 patients on the protocol NHL-BFM-90 died after short-term improvement. None of them achieved remission. Of 10 patients with newly diagnosed ABLL treated according to NHL-BFM-90 protocol, remission was achieved in 4 patients, follow-up median--34 months (2-56). Six patients died: 4 of progression, 2 of chemotherapy complications. BLL-M-04 therapy was made in 9 patients: 7 patients persisted on the first remission, 2 patients died of chemotherapy complications. Overall duration of the treatment was 3-3.5 months.. The protocol ABLL-M-04 seems to be more effective than a classic NHL-BFM-90, but this must be supported by more cases. CHOP therapy cannot be recommended for patients with ABLL because of poor efficacy (all the CHOP patients died).

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Burkitt Lymphoma; Cyclophosphamide; Daunorubicin; Disease Progression; Dose-Response Relationship, Drug; Doxorubicin; Female; Follow-Up Studies; Humans; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisolone; Prednisone; Retrospective Studies; Severity of Illness Index; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; 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

Burkitt's lymphoma is a rare aggressive lymphoma, which responds poorly to standard chemotherapy regimens used to treat high-grade non-Hodgkin's lymphoma (NHL). The use of intensive chemotherapy protocols using alkylating agents and intensive CNS prophylaxis has dramatically altered prognosis. We have treated eight patients with Burkitt's lymphoma with a modified BFM protocol. The dose of methotrexate was reduced from 5 g/m2 to 1.5 g/m2 with the aim of reducing toxicity. Seven patients received a total of six cycles of chemotherapy each and one patient received five cycles of chemotherapy. Each cycle included high-dose methotrexate, an alkylating agent (ifosphamide or cyclophosphamide) and two triple intrathecal injections of chemotherapy. Two patients with bulky abdominal disease in addition received an autologous stem cell transplant. The regimen was well tolerated with minimal toxicity. At a median follow-up of 16 months (range 10-28), six of the eight patients (75%) were alive and in complete remission. Two patients relapsed, one 24 months post-BFM chemotherapy and the other 1-month post-autologous stem cell transplantation and 2 months post-BFM chemotherapy.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Burkitt Lymphoma; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Disease-Free Survival; Female; Granulocyte Colony-Stimulating Factor; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Humans; Infections; Lymphoma, AIDS-Related; Male; Mercaptopurine; Methotrexate; Prednisone; Recurrence; Remission Induction; Treatment Outcome; Vincristine

Topics: Ankle Injuries; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Burkitt Lymphoma; Casts, Surgical; Child; Follow-Up Studies; Fractures, Bone; Humans; Male; Mercaptopurine; Methotrexate; Pain; Prednisone; Remission Induction; Vincristine; Wrist Injuries

To evaluate the prognostic implications of the presence of minimal residual disease (MRD) during the induction period in children diagnosed with low risk B cell precursor acute lymphoblastic leukaemia (LR-ALL).. In 36 children with LR-ALL treated with BFM-86 protocol, MRD was studied at the end of induction by IgH and TCR delta gene analysis.. The probabilities of disease free survival were: 52% (patients with MRD at the end of Induction), 64% (patients with MRD at day 15) and 100% (patients without MRD).. The presence of MRD is a new and useful prognostic factor in LR childhood ALL.

Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Burkitt Lymphoma; Child; Cyclophosphamide; Cytarabine; DNA Primers; Genes, T-Cell Receptor delta; Humans; Mercaptopurine; Methotrexate; Molecular Sequence Data; Neoplasm, Residual; Polymerase Chain Reaction; Prednisone; Prognosis; Recurrence; Retrospective Studies; Risk Factors; Sensitivity and Specificity; Vincristine

Topics: Antimetabolites, Antineoplastic; Burkitt Lymphoma; Child; Humans; Male; Mercaptopurine; Methotrexate; Piperacillin; Pseudomonas Infections; Seizures; Sepsis; Staphylococcal Infections

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

To prevent drug resistance, the authors designed a protocol that featured early intensive rotating drug pairs as part of the therapy for acute lymphoblastic leukemia (ALL).. After prednisone, vincristine, asparaginase, and daunorubicin induction, 12 intensive treatments (ABACABACABAC) were given in 30 weeks: A--intermediate-dose methotrexate (IDMTX) plus intermediate-dose mercaptopurine (MP); B--cytosine arabinoside (AC) plus daunorubicin (DNR); C--AC plus teniposide (VM-26). Triple intrathecal chemotherapy (AC, MTX, and hydrocortisone) was given for central nervous system (CNS) prophylaxis. Continuation therapy consisted of weekly MTX and daily MP until 2.5 years of continuous complete remission had been achieved.. Seventy-four children (age range, 1-19 years) at high risk of relapse were treated. Of 55 with B-lineage (early pre-B, pre-B) ALL, 24 have failed (2 induction failures, 2 deaths from infection, and 20 relapses). The event-free survival (EFS) rate at 4 years was 55.5% (standard error [SE] +/- 7.7%). Of 19 patients with T-cell ALL, 12 have failed (2 induction failures and 10 relapses). The EFS rate at 4 years was 32.6% (SE +/- 26.8%). Toxicities were significantly more common after AC and DNR or AC and VM-26 than IDMTX and MP. There were no toxicity-related deaths during intensive treatments.. Early intensive rotating therapy is tolerable and warrants consideration for additional trials of patients with high-risk, B-lineage ALL.

Topics: Administration, Oral; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Child; Child, Preschool; Cytarabine; Daunorubicin; Drug Administration Schedule; Female; Humans; Hydrocortisone; Infant; Injections, Intramuscular; Injections, Intravenous; Injections, Spinal; Leukemia-Lymphoma, Adult T-Cell; Male; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Teniposide; Treatment Failure

Topics: Burkitt Lymphoma; Cell Division; Cell Survival; Cells, Cultured; DNA, Neoplasm; Fluorouracil; Heparin; Humans; Mechlorethamine; Mercaptopurine; Methotrexate; Thymidine; Time Factors; Tritium

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: Animals; Antineoplastic Agents; Burkitt Lymphoma; Culture Techniques; Humans; Leukemia; Leukemia L1210; Leukemia, Experimental; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Mercaptopurine; Methotrexate; Mice; Prednisolone; Vincristine

Topics: Antineoplastic Agents; Asparaginase; Burkitt Lymphoma; Choriocarcinoma; Cyclophosphamide; Cytarabine; Dactinomycin; Daunorubicin; Female; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Melphalan; Mercaptopurine; Methotrexate; Prednisone; Pregnancy; Vincristine; Wilms Tumor

Topics: Adolescent; Adult; Age Factors; Aged; Antineoplastic Agents; Burkitt Lymphoma; Child; Child, Preschool; Cytarabine; Daunorubicin; Female; Humans; Infant; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Prognosis; Thioguanine; Time Factors; Vincristine

Topics: Antineoplastic Agents; Asparaginase; Burkitt Lymphoma; Cyclophosphamide; Cytarabine; Daunorubicin; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Nitroso Compounds; Prednisone; Urea; Vincristine