mercaptopurine and Lymphoma

The risk of lymphoma in patients with inflammatory bowel disease (IBD) treated with anti-TNF agents remains unclear.. To assess the comparative risk of lymphoma with anti-TNF agents and/or thiopurines in IBD METHODS: We searched PubMed, EMBASE and Cochrane Library to identify studies that evaluated lymphoproliferative disorders associated with anti-TNF agents with or without thiopurines. The risk of lymphoma was assessed through four comparator groups: combination therapy (anti-TNF plus thiopurine), anti-TNF monotherapy, thiopurine monotherapy and control group. Pooled incidence rate ratios (IRR) were estimated through Poisson-normal models.. Four observational studies comprising 261 689 patients were included. As compared with patients unexposed to anti-TNF and thiopurines, those exposed to anti-TNF monotherapy, thiopurine monotherapy or combination therapy had pooled IRR (per 1000 patient-years) of lymphoma of 1.52 (95% CI: 1.06-2.19; P = 0.023), 2.23 (95% CI: 1.79-2.79; P < 0.001) and 3.71 (95% CI: 2.30-6.00; P ≤ 0.01), respectively. The risk of lymphoma associated with combination therapy was higher than with thiopurines or anti-TNF alone with pooled IRR of 1.70 (95% CI: 1.03-2.81; P = 0.039) and 2.49 (95% CI: 1.39-4.47; P = 0.002), respectively. The risk did not differ between anti-TNF monotherapy and thiopurine monotherapy with pooled IRR of 0.72 (95% CI: 0.48-1.07; P = 0.107). All observational studies were of high quality according to the Newcastle-Ottawa scale.. There is an increased risk of lymphoma in IBD patients treated with anti-TNF agents, either alone or when combined with thiopurines.

Topics: Adult; Colitis; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Lymphoma; Male; Mercaptopurine; Middle Aged; Risk Assessment; Risk Factors; Tumor Necrosis Factor-alpha

Crohn's disease (CD) is a chronic inflammatory disease that confers a higher risk of cancer than in the general population. New, large, population-based studies in the past decade show that patients with CD are at higher risk of colorectal, small bowel, melanoma, and cervical cancer. Patients who use thiopurines are at additional risk of development of lymphoma and nonmelanoma skin cancer. Preventive surveillance for cancers of the colorectum, skin, and uterine cervix is advised.

Topics: Colorectal Neoplasms; Crohn Disease; Early Detection of Cancer; Female; Humans; Immunosuppressive Agents; Intestinal Neoplasms; Intestine, Small; Lymphoma; Male; Melanoma; Mercaptopurine; Risk Factors; Skin Neoplasms; Uterine Cervical Neoplasms

Thiopurine therapy for inflammatory bowel disease (IBD) has been associated with increased risk for lymphoma. We estimated the relative risk of lymphoma in patients with IBD exposed to thiopurines and compared relative risk values derived from population-based studies with those from referral center-based studies. We investigated whether active use increased risk compared with past use, and whether sex, age, or duration of use affects risk of lymphoma.. We searched MEDLINE, EMBASE, and Cochrane databases, as well as conference abstracts and international publications, for the terms "6-MP and lymphoma," "6-mercaptopurine and lymphoma," "thiopurines and lymphoma," "azathioprine and cancer and IBD," "azathioprine and malignancy and IBD," "azathioprine and lymphoma," and "lymphoproliferative and thiopurines." Pooled standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were estimated. The deviance statistic from Poisson models was used to calculate heterogeneity.. Eighteen studies (among 4383 citations) met our inclusion criteria. Overall, the SIR for lymphoma was 4.92 (95% CI, 3.10-7.78), ranging from 2.80 (95% CI, 1.82-4.32) in 8 population studies to 9.24 (95% CI, 4.69-18.2) in 10 referral studies. Population studies demonstrated an increased risk among current users (SIR = 5.71; 95% CI, 3.72-10.1) but not former users (SIR = 1.42; 95% CI, 0.86-2.34). Level of risk became significant after 1 year of exposure. Men have a greater risk than women (relative risk = 1.98; P < .05); both sexes were at increased risk for lymphoma (SIR for men = 4.50; 95% CI = 3.71-5.40 and SIR for women = 2.29; 95% CI = 1.69-3.05). Patients younger than 30 years had the highest relative risk (SIR = 6.99; 95% CI, 2.99-16.4); younger men had the highest risk. The absolute risk was highest in patients older than 50 years (1:354 cases per patient-year, with a relative risk of 4.78).. Compared with studies from referral centers, population-based studies of IBD patients show a lower but significantly increased risk of lymphoma among patients taking thiopurines. The increased risk does not appear to persist after discontinuation of therapy. Patients over 50 have the highest absolute risk of lymphoma per year on thiopurines, while men under 35 may also be a high risk group. More study is needed to precisely understand groups highest at risk. The risks of lymphoma and potential benefits of therapy should be considered for all patients with IBD.

Topics: Adult; Aged; Azathioprine; Female; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Lymphoma; Male; Mercaptopurine; Middle Aged; Risk; Risk Assessment; Young Adult

The lymphoproliferative disorders (LDs) are a heterogeneous group of at least 70 conditions that result from the clonal proliferation of B, T, and NK cells. Inflammatory bowel disease (IBD)-associated lymphomas are typically B-cell LD, while T-cell or Hodgkin's lymphomas are rare. In IBD patients not on immunosuppression, the risk of LD seems to be similar or slightly higher than the background population risk. Thiopurine therapy is associated with an increased risk: the relative risk is increased four- to sixfold and the absolute risk varies between 1 in 4000-5000 for those aged 20-29 to 1 in 300-400 in those over 70. It is difficult to quantify the risk of anti- tumor necrosis factor (TNF) therapy alone; however, it appears to be less than for thiopurines alone. There is particular concern regarding the development of post-transplant-like LD in those with latent epstein-barr virus (EBV) infection exposed to immunosuppressives, the occurrence of hepatosplenic T cell lymphoma in patients treated with combination anti-TNF and thiopurine therapy, and the development of hemophagocytic lymphohistiocytosis in those who acquire a primary EBV or other infections while on immunosuppressive medication. There are currently no guidelines for monitoring EBV (or other virus) status in patients on immunosuppression, although it could be used to monitor those who have a prior history of lymphoma and are about to start a thiopurine or anti-TNF agent. In discussing the risks of lymphoproliferative disorders associated with agents used for the treatment of IBD, patients can often be reassured that the benefits of such therapy still outweigh the small, but real, risks.

Topics: Age Factors; Azathioprine; Epstein-Barr Virus Infections; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Lymphohistiocytosis, Hemophagocytic; Lymphoma; Lymphoproliferative Disorders; Mercaptopurine; Risk Factors; Tumor Necrosis Factor-alpha

The immunomodulators (6-mercaptopurine, azathioprine and methotrexate) and biologics (infliximab, adalimumab, certolizumab and natalizumab) are medications essential in the management of pediatric inflammatory bowel disease. If properly utilized, these medications can control active disease, reduce corticosteroid exposure, induce remission, and promote normal growth and development. However, these medications also have significant toxicity and increase the risk of infections and lymphoma. This article provides information about the safety and efficacy of these medications in the treatment of children with Crohn's disease and ulcerative colitis.

Topics: Antibodies, Monoclonal; Child; Colitis, Ulcerative; Crohn Disease; Humans; Immunologic Factors; Infections; Lymphoma; Mercaptopurine; Treatment Outcome

Inflammatory bowel disease (IBD) is commonly treated with immunomodulators such as azathioprine and 6-mercaptopurine (6-MP). Studies examining lymphoma risk in IBD patients treated with these medications have been underpowered and have yielded conflicting conclusions.. The purpose of this meta-analysis was to provide a more precise estimate of the relative risk of lymphoma among IBD patients treated with azathioprine or 6-MP.. Studies were included if they were English language, full article, cohort studies specifically designed to evaluate cancer as an adverse outcome of treatment with azathioprine or 6-MP. Pooled standardised incidence ratios were calculated to estimate the relative risk of lymphoma associated with therapy. Heterogeneity was assessed using Poisson regression. Sensitivity analyses examined the influence of individual studies on risk estimate and heterogeneity statistics.. Six studies were identified that met our inclusion criteria. When the data were combined across all studies, the pooled relative risk was 4.18 (95% confidence interval 2.07-7.51; 11 observed cases, 2.63 expected). Sensitivity analysis showed that exclusion of any one study had a relatively small effect on the pooled relative risk estimate (range 3.49-5.21) but excluding either the study with the highest or lowest estimated relative risk eliminated the statistically significant heterogeneity.. Our data suggest an approximate fourfold increased risk of lymphoma in IBD patients treated with azathioprine/6-MP. The increased risk of lymphoma could be a result of the medications, the severity of the underlying disease, or a combination of the two.

Topics: Azathioprine; Female; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Lymphoma; Male; Mercaptopurine; Risk Factors

Intrathecal chemotherapy with antineoplastic agents is mainly utilised in children with leukaemia and lymphoma, and in selected brain tumours. In these diseases, intrathecal use is restricted to methotrexate (MTX), cytosine arabinoside (Ara-C) and corticosteroids. A number of other agents are, at the present time, under evaluation. Intrathecal MTX administered sequentially with systemic high dose MTX infusion prolongs therapeutic cerebral spinal fluid (CSF) levels of the drug. Prolonged therapeutic CSF levels can also be achieved by giving repeated small intrathecal doses of MTX over an extended period in selected patients, with an implanted Ommaya reservoir. In the CSF, the metabolic inactivation of Ara-C is significantly lower than in plasma with a CSF clearance similar to the rate of CSF bulk flow. A slow-release formulation of Ara-C may be given intrathecally, resulting in a prolonged cytotoxic concentration in the CSF. CNS relapse and neurotoxicity in patients with acute lymphoblastic leukaemia, especially younger children, may be reduced by using age-related dosing of intrathecal MTX and Ara-C. Hydrocortisone is used in combination with MTX and Ara-C for so-called 'triple intrathecal chemotherapy' in the treatment of meningeal leukaemia. Intrathecal thiotepa does not appear to be advantageous over systemic administration in patients with brain and meningeal leukaemia. Monoclonal antibodies, reactive with tumour-associated antigens, can be used as delivery systems for chemotherapeutic agents and radionuclides. However, the development of this new approach is currently under evaluation in larger clinical studies. Neurological adverse effects may be expected with intrathecal chemotherapy and are increased by high dose systemic therapy, concomitant cranial radiotherapy or meningeal infiltration by neoplastic cells. Inadvertant intrathecal administration of antineoplastic agents that are indicated for systemic administration only, is dangerous and may result in a fatal outcome.

Topics: Adrenal Cortex Hormones; Antineoplastic Agents; Blood-Brain Barrier; Cerebellar Neoplasms; Cerebrospinal Fluid; Child; Cytarabine; Humans; Injections, Spinal; Lymphoma; Medulloblastoma; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Thiotepa

Lymphoma complicating inflammatory bowel disease is well described. Whether the risk of lymphoma is increased by immunosuppressive treatment with azathioprine, 6-mercaptopurine or infliximab is a common concern among patients and physicians considering using these agents. This review aims to quantify the lymphoma risk in inflammatory bowel disease and the added risk attributable to these treatments. The evidence from published cases is that lymphomas occur at sites of active inflammatory bowel disease more often than expected for this to be a chance association. Studies on inflammatory bowel disease populations are conflicting, with some follow-up studies from large inflammatory bowel disease clinics showing an increase in lymphoma incidence, while other population-based studies show little or no increase in risk of lymphoma. A small increase in lymphoma risk in inflammatory bowel disease, perhaps 2-3-fold, may be compatible with both sets of data. Studies of the risks associated with immuno- suppression are less satisfactory, with smaller numbers of patients and relatively short follow-up. The available evidence would support a further increase in lymphoma risk associated with immunosuppressive treatment in inflammatory bowel disease of around fivefold compared to no immunosuppressive use, and tenfold compared to the general population. The risks appear to be less than that associated with renal and hepatic transplant-related immunosuppression. Infliximab treatment is still too new to make a full assessment of its long-term safety, but post-marketing surveillance currently suggests that lymphoma risk may not be any greater than that associated with azathioprine and 6-mercaptopurine. Population-wide surveillance for lymphoma in inflammatory bowel disease would be required to narrow the confidence intervals on these estimates of lymphoma risk in inflammatory bowel disease and immunosuppressive treatment.

Topics: Antibodies, Monoclonal; Azathioprine; Epidemiologic Studies; Gastrointestinal Agents; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Infliximab; Lymphoma; Mercaptopurine; Risk Factors; Tumor Necrosis Factor-alpha

Topics: Acquired Immunodeficiency Syndrome; Animals; Antibody Formation; Autoimmune Diseases; Cyclophosphamide; Herpesviridae Infections; Humans; Immunization, Passive; Immunoglobulin Idiotypes; Immunosuppression Therapy; Immunosuppressive Agents; Leukemia; Lymphoma; Mercaptopurine; Sarcoma, Kaposi; T-Lymphocytes; Transplantation Immunology

Topics: Adrenal Cortex Hormones; Alkylating Agents; Animals; Antineoplastic Agents; Asparaginase; Choriocarcinoma; Dactinomycin; Female; Folic Acid Antagonists; History, 19th Century; History, 20th Century; Humans; Leukemia, Lymphoid; Lymphoma; Mercaptopurine; Neoplasms; Pregnancy

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: Abnormalities, Multiple; Abortion, Spontaneous; Collagen Diseases; Cyclophosphamide; Female; Gastrointestinal Diseases; Hematologic Diseases; Immune System Diseases; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Diseases; Kidney Function Tests; Leukopenia; Liver Function Tests; Lymphoma; Mercaptopurine; Methotrexate; Nervous System Diseases; Pregnancy

Topics: Animals; Animals, Newborn; Antilymphocyte Serum; Antimetabolites; Azathioprine; Carcinogens; Cell Division; Graft vs Host Reaction; Histocompatibility Antigens; Humans; Immunity, Cellular; Immunosuppression Therapy; Immunosuppressive Agents; Lymphoma; Mercaptopurine; Mice; Mice, Inbred C57BL; Mice, Inbred NZB; Oncogenic Viruses; Procarbazine; Skin Neoplasms; Thymectomy

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: Adenocarcinoma; Animals; Antineoplastic Agents; Bone Marrow; Bone Marrow Cells; Cell Division; Cyclophosphamide; Cytarabine; Female; Fluorouracil; Humans; Leukemia L1210; Leukemia, Lymphoid; Lymphoma; Melphalan; Mercaptopurine; Methotrexate; Mice; Multiple Myeloma; Neoplasms; Nitrogen Mustard Compounds; Prednisone; Pregnancy; Time Factors; Trophoblastic Neoplasms; Vinblastine

Topics: Adrenal Cortex Hormones; Aminopterin; Antineoplastic Agents; Asparaginase; Child; Child, Preschool; Chlorambucil; Cyclophosphamide; Cytarabine; Daunorubicin; Fluorouracil; Humans; Leukemia; Lymphoma; Mercaptopurine; Methotrexate; Nitrogen Mustard Compounds; Procarbazine; Sarcoma; Vinblastine; Vincristine

Topics: Adult; Antineoplastic Agents; Asparaginase; Carmustine; Child; Cyclophosphamide; Cytarabine; Cytosine; Daunorubicin; Drug Therapy, Combination; Hodgkin Disease; Humans; Immunotherapy; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma; Male; Mechlorethamine; Mercaptopurine; Methotrexate; Nitrogen Mustard Compounds; Prednisolone; Prednisone; Procarbazine; Remission, Spontaneous; Vincristine

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Chloroquine; Cyclophosphamide; Cytarabine; Drug Synergism; Fluorouracil; Humans; Japan; Leukemia; Lymphoma; Mercaptopurine; Mitomycins; Neoplasms; Podophyllin; Prednisolone; Thiotepa; Vincristine; Vitamin K 1

Topics: Breast Neoplasms; Clinical Trials as Topic; Gastrointestinal Neoplasms; Humans; Lung Neoplasms; Lymphoma; Melanoma; Mercaptopurine; Neoplasms

Immunomodulator therapy (e.g., thiopurines) has been linked to an increased malignancy risk, in patients with inflammatory bowel diseases (IBDs), which increases with treatment duration, based on studies mainly in Caucasian patients. However, our previous real-world study, of Japanese patients with IBDs, indicated no overall increased risk of non-Hodgkin lymphoma (NHL) with thiopurine treatment.. This subanalysis investigated the influence of thiopurine IBD treatment dose and duration, on incidence of NHL in Japanese patients.. The Medical Data Vision (MDV) claims database (17.8 million patients; April 2008-January 2018) was used to analyze incidence rate ratios (IRRs) of NHL, in eligible patients (≥1 diagnosis of ulcerative colitis or Crohn's disease) and no malignancy at diagnosis or first prescription of a thiopurine. Age- and sex-adjusted IRRs and 95% confidence interval for NHL were calculated as the incident cases compared in the subgroups versus the overall IBD population.. Among 75,673 patients with IBDs, 103 cases of NHL were recorded. There was no overall increase in the risk of developing NHL among Japanese patients treated with thiopurines. The IRRs relative to the overall IBD population were 1.88, 1.42, and 0.38 for <1 year, 1-3 years, and ≥3 years of thiopurine treatment. There were no differences in NHL incidence when grouping patients by mean daily thiopurine dose prescribed, age, or disease subgroups.. Dose or duration of thiopurine treatment did not explain a lack of increased risk of NHL with thiopurine use in Japanese patients with IBDs.

Topics: Azathioprine; Duration of Therapy; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Japan; Lymphoma; Mercaptopurine; Risk Factors

Thiopurines are widely used to maintain remission in both ulcerative colitis (UC) and Crohn's disease (CD). Reported effectiveness and tolerability rates have been variable across studies. There are only sparse data in Asian population regarding the long-term efficacy and safety of thiopurines.. Records of 5351 patients followed up at inflammatory bowel disease (IBD) clinic, All India Institute of Medical Sciences, New Delhi from 2004 to 2020 were evaluated retrospectively. Safety was evaluated in terms of long-term adverse events and development of malignancy.. Of 5351 patients with IBD, 1093 who received thiopurine for > 3 months (UC = 788 [proctitis-1.9%, left-sided colitis-44.9%, & pancolitis-53.1%] & CD = 305 [inflammatory-42.6%, stricturing-46.9%, & fistulizing-10.5%]) were included (60.8%-male patients). Follow up and treatment duration on thiopurine were 7 (4-12) years and 39.4 ± 40.3 months, respectively, with 254 (23.2%) patients receiving thiopurines for more than 5 and 68 (6.2%) receiving for more than 10 years. Three hundred and fifty-nine (UC: 249 [31.6%]; CD: 110 [36.1%]; P = 0.1) patients developed adverse events; commonest was myelosuppression (23.4%) followed by gastrointestinal intolerance (3%), flu-like illness (1.7%), and arthralgia/myalgia (1.4%). Myelosuppression was the commonest cause of thiopurine withdrawal. No patient (including 254 patients on thiopurine for ≥ 5 years) developed lymphoma or non-melanoma skin cancer. The cumulative probability of staying free from adverse events in overall IBD cohort at 1, 2, and 5 years was 78.6%, 71.9%, and 68.4%, respectively, and this was comparable between UC and CD (P = 0.09).. Long-term follow up of patients with IBD from northern India on thiopurine monotherapy demonstrated minimal risk of development of lymphoma as well as non-melanoma skin cancer.

Topics: Azathioprine; Cohort Studies; Colitis, Ulcerative; Crohn Disease; Humans; India; Inflammatory Bowel Diseases; Lymphoma; Male; Mercaptopurine; Retrospective Studies; Risk Factors; Skin Neoplasms

Epstein Barr virus (EBV) is a human herpes virus that infects 90% of the world's population and has been linked to the development of lymphoproliferative disorders (LPDs) and immunosuppression. Primary EBV infection in patients with IBD on thiopurines is a risk factor for LPD, including lymphoma. We aimed to describe EBV status in a pediatric population with IBD with an emphasis on those initiating thiopurines.. Electronic medical records and EBV serologies were reviewed and categorized into asymptomatic screening versus suspicion for acute infection. EBV status before therapy was described by sex, age, and therapeutic regimen. Descriptive statistics and univariate analysis were employed.. Only 150 (22%) of our 688 pediatric patients with IBD had documented EBV status regardless of age or treatment regimen. Only 17% were assessed for suspicion of acute infection and 83% for screening. Sixty-four (52%) screened patients were checked before starting any treatment and only 40% were immunoglobulin (Ig)G positive. There was no difference in mean age between the seronegative and seropositive group. The majority (63%) of thiopurine-treated patients were IgG negative before starting therapy. Eighty percent of primary EBV infections occurred on thiopurines at a mean (SD) of 2 ± 1.5 years after initiating therapy.. The majority of our pediatric patients with IBD with documented EBV status were IgG negative at thiopurine initiation. Thiopurines were also associated with primary EBV infection. EBV status may be an important determinate of whether physicians prescribe thiopurines given the risk of primary EBV infections and lymphoproliferative diseases.

Topics: Adolescent; Child; Cross-Sectional Studies; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Lymphoma; Male; Mercaptopurine; New York City; Retrospective Studies; Viral Load; Young Adult

Topics: Antibodies, Monoclonal; Azathioprine; Colitis, Ulcerative; Female; Humans; Immunosuppressive Agents; Lymphoma; Male; Mercaptopurine

Topics: Antibodies, Monoclonal; Azathioprine; Colitis, Ulcerative; Female; Humans; Immunosuppressive Agents; Lymphoma; Male; Mercaptopurine

There is controversy over whether the treatment of patients with ulcerative colitis (UC) with thiopurines increases their risk of lymphoma. We evaluated the risk of lymphoma (ongoing, residual, and per year of therapy) among thiopurine-treated patients with UC.. We obtained nationwide data from the Veterans Affairs (VA) health care system from 2001 to 2011. We performed a retrospective cohort study, analyzing data on 36,891 patients from their date of diagnosis of UC in the VA health care system to a diagnosis of lymphoma or October 1, 2011 (subjects followed up for a median of 6.7 years). Thiopurine exposure was assessed using the VA pharmacy database. Patients who developed lymphoma were identified based on ICD-9 codes and confirmed by manual chart review.. In total, 4734 patients with UC (13%) were treated with thiopurines for a median of 1 year. Lymphoma developed in 119 patients who had not been treated with thiopurines, 18 who were treated with thiopurines, and 5 who had discontinued treatment with thiopurines. The incidence rates of lymphoma were 0.60 per 1000 person-years among patients who had not been treated with thiopurines, 2.31 among patients who were treated with thiopurines, and 0.28 among patients who had discontinued treatment with thiopurines. The incidence rates of lymphoma during the first year, second year, third year, fourth year, and >4 years of thiopurine therapy were 0.9, 1.6, 1.6, 5, and 8.9 per 1000 person-years, respectively. The age-, sex-, and race-adjusted hazard ratios of developing lymphoma were 4.2 (95% confidence interval, 2.5-6.8; P < .0001) while being treated with thiopurines and 0.5 (95% confidence interval, 0.2-1.3; P = .17) after discontinuing treatment with thiopurines compared with patients who had not been treated with thiopurines.. Based on a retrospective, nationwide cohort study, patients with UC have a 4-fold increase in risk of lymphoma while being treated with thiopurines compared with patients who have not been treated with thiopurines. The risk increases gradually for successive years of therapy. Discontinuing thiopurine therapy reduces the risk of lymphoma.

Topics: Adult; Aged; Antibodies, Monoclonal; Azathioprine; Cohort Studies; Colitis, Ulcerative; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Incidence; Infliximab; Lymphoma; Male; Mercaptopurine; Middle Aged; Proportional Hazards Models; Reproducibility of Results; Retrospective Studies; Risk Factors; United States; United States Department of Veterans Affairs

Topics: Antibodies, Monoclonal; Azathioprine; Colitis, Ulcerative; Female; Humans; Immunosuppressive Agents; Infliximab; Lymphoma; Male; Mercaptopurine

6-Mercaptopurine (6-MP) and azathioprine (AZA) are effective for induction and maintenance therapy of Crohn's disease (CD) and ulcerative colitis (UC). There is an increased risk of lymphoma in patients with inflammatory bowel disease (IBD) treated with 6-MP/AZA. Little, however, is known about the prognosis of IBD patients treated with 6-MP/AZA who develop lymphoma.. We conducted a retrospective review of 8780 records from three tertiary IBD centers and the records of 600 lymphoma patients from an academic Hematology and Oncology Center. The primary endpoint variable was survival of IBD patients with a lymphoma diagnosis treated or not treated with 6-MP/AZA. A secondary endpoint was the relative survival rate (by gender, race, and ethnicity) extrapolated from the Surveillance Epidemiology and End Results (SEER) database, computed for each subject.. Fourteen IBD patients were diagnosed with lymphoma. Twelve had CD and two had UC. Seven patients had treatment with 6-MP/AZA and seven had not. Two patients who received 6-MP/AZA died (both 1 year after diagnosis) and two patients who had not received 6-MP/AZA died (one after 2 years, another 3 years after diagnosis), all from lymphoma. Survival at last follow-up was similar to expected survival based on extrapolated SEER data for both 6-MP/AZA treated and untreated patients.. We found no differences of survival with lymphoma between IBD patients and expected survival for the general population. Also, the prognosis for those IBD patients treated with 6-MP/AZA was not worse than lymphoma patients not treated with 6-MP/AZA. Statistical analysis, however, was limited by the small sample size and heterogeneity of the patients studied.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Azathioprine; Colitis, Ulcerative; Crohn Disease; Female; Follow-Up Studies; Humans; Lymphoma; Male; Mercaptopurine; Middle Aged; Prognosis; Retrospective Studies; Survival Rate; Tertiary Care Centers; Young Adult

We describe here the case of a 7-year old girl with lymphoma who developed life-threatening toxicities upon cytarabine plus mercaptopurine. Surprisingly, initial investigations on canonical thiopurine methyltransferase genetic polymorphism proved to be negative. We focused next on deregulations affecting the CDA gene implicated in the liver disposition of cytarabine. This patient was homozygous for both the 79A>C and the -31delC polymorphisms on the CDA gene and promoter, two genotypes with reported opposite effects on CDA phenotype. To determine the CDA status of this patient, additional functional testing was performed and eventually demonstrated that this patient was a poor metabolizer. This case demonstrates that besides affecting thiopurine methyltransferase, dysregulations with CDA should be screened to anticipate toxicities with the cytarabine plus mercaptopurine combination.

Topics: Child; Cytarabine; Cytidine Deaminase; Drug Combinations; Exons; Female; Homozygote; Humans; Lymphoma; Mercaptopurine; Methyltransferases; Point Mutation; Polymorphism, Genetic; Promoter Regions, Genetic; Sequence Deletion

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

Prospective follow-up for a median of 35 months of a French cohort of 19 486 patients with inflammatory bowel disease showed a nearly 4-fold increase in the risk of lymphoma in patients exposed to azathioprine or mercaptopurine (relative risk 3.75; 95% confidence interval 1.59 to 8.85). This risk should be taken into account when weighing the likely benefits of these drugs in treatment of patients with severe chronic inflammatory bowel disease no longer responding to first-line treatment.

Topics: Azathioprine; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Lymphoma; Mercaptopurine

Immune suppressant medications such as thiopurines and anti-tumor necrosis factor agents are important for maintaining disease control in most patients with inflammatory bowel diseases (IBDs); however, their use has been associated with the development of malignant lymphoma. The purpose of this Dutch nationwide study was to estimate the relative risk of malignant lymphoma in IBD patients.. IBD patients who developed a lymphoma between 1997 and 2004 were identified using the Dutch National Database of PALGA. Data from confirmed cases were collected from individual hospitals, including data on Epstein-Barr virus (EBV). The age-adjusted 8-year incidence of malignant lymphoma in the Netherlands was retrieved from the Central Bureau of Statistics.. Forty-two hospitals were visited and 285 matches evaluated in the total cohort of 17,834 IBD patients. Forty-four lymphomas were observed, resulting in a relative risk of 1.27 (95% confidence interval [CI]: 0.92-1.68). Only 19 of 44 patients (43%) were exposed to azathioprine/6-mercaptopurine (AZA/6-MP). Remarkably, 92% of patients (11/12) with EBV-positive lymphoma used AZA/6-MP, in contrast to only 19% patients (4/21) with EBV-negative lymphoma, suggesting a strong relation between EBV-positive lymphoma and thiopurine use.. This nationwide study does not suggest a significant overall increased risk for lymphoma in IBD patients. A distinct correlation between EBV-positive lymphoma and AZA/6-MP use was observed.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Azathioprine; Case-Control Studies; Child; Child, Preschool; Cohort Studies; Epstein-Barr Virus Infections; Female; Follow-Up Studies; Herpesvirus 4, Human; Humans; Immunosuppressive Agents; Incidence; Infant; Infant, Newborn; Inflammatory Bowel Diseases; Lymphoma; Male; Mercaptopurine; Middle Aged; Netherlands; Prognosis; Risk Factors; Survival Rate; Young Adult

The objective of this study was to assess inflammatory bowel disease (IBD) medications in relation to lymphoma risk.. Information on IBD and relevant medications and other utilization was obtained from the Kaiser Permanente IBD Registry, 1996-2009. Lymphoma cases were ascertained from the Kaiser Permanente Cancer Registry. Lymphoma incidence was compared between the IBD cohort and the general Kaiser Permanente population.. Of the 16,023 IBD patients without human immunodeficiency virus followed an average 5.8 years, 43 developed lymphoma. IBD patients with and without lymphoma did not differ with respect to past IBD-related visits, procedures, or tests. The standardized incidence rate ratio (SIRR) for lymphoma among IBD patients with no dispensing of thiopurine or anti-tumor necrosis factor (TNF) was 1.0 (95% confidence interval (CI): 0.96-1.1). Of the 21,282 person-years involving exposure to thiopurine or anti-TNF, 81% involved thiopurine alone; 3%, anti-TNF alone; and 16%, combination therapy. Among patients with thiopurine but not anti-TNF dispensings, the SIRR was 0.3 (95% CI: 0.2-0.4) for past use and 1.4 for current use (95% CI: 1.2-2.7). Among patients with dispensing of anti-TNF (with and without thiopurine), the SIRR was 5.5 for past use (95% CI: 4.5-6.6) and 4.4 for current use (95% CI: 3.4-5.4). The most common lymphoma subtypes were diffuse large B-cell lymphoma (44%), follicular lymphoma (14%), and Hodgkin's disease (12%).. Our study provides evidence that IBD alone is not associated with the risk of lymphoma. Use of anti-TNF with thiopurine and current use of thiopurine alone were associated with increased risk, although the effect of disease severity merits further evaluation.

Topics: Adalimumab; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Azathioprine; Child; Child, Preschool; Cohort Studies; Drug Therapy, Combination; Female; Humans; Incidence; Infant; Infant, Newborn; Inflammatory Bowel Diseases; Infliximab; Lymphoma; Male; Mercaptopurine; Middle Aged; Risk Factors; Tumor Necrosis Factor-alpha; Young Adult

FK228 is a novel antitumor depsipeptide that inhibits histone deacetylases and restores the expression of genes aberrantly suppressed in cancer cells. This agent was shown to have broad antitumor activity in preclinical studies, and is currently under phase I/II evaluations. Because of its wide spectrum of actions, it is reasonable to consider the combination with other anticancer drugs in clinical application. We studied the cytotoxic interaction of FK228 in combination with conventional antileukemic agents using human promyelocytic leukemia HL60, Philadelphia chromosome-positive (Ph(+)) chronic myelogenous leukemia KU-812, T-cell lymphoblastic leukemia MOLT3 and Burkitt's lymphoma Raji cell lines. For the combination of FK228 and imatinib, Ph(+) leukemia KU812, K562 and TCC-S cell lines were used. The cells were exposed simultaneously to FK228 and other agents for 4 days. Cell growth inhibition was determined by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. We used the isobologram method of Steel and Peckham to evaluate the cytotoxic interaction at the concentration of drugs that produced 80% cell growth inhibition (IC(80)). FK228 showed an additive effect with cytarabine, carboplatin, doxorubicin, etoposide, 4-hydroperoxy-cyclophosphamide, 6-mercaptopurine and SN-38 (active metabolite of irinotecan) in all cell lines studied. FK228 with methotrexate and vincristine showed an antagonistic effect in three and one of the four cell lines, respectively. FK228 was additive with imatinib in all three Ph(+) leukemia cells. Our findings suggest that FK228 is a promising candidate for combining with most anticancer agents except for methotrexate and vincristine, which produce suboptimal effects.

Topics: Antineoplastic Agents; Apoptosis; Benzamides; Camptothecin; Carboplatin; Cell Line, Tumor; Cell Survival; Cyclophosphamide; Cytarabine; Depsipeptides; Dose-Response Relationship, Drug; Doxorubicin; Drug Synergism; Etoposide; Histone Deacetylase Inhibitors; HL-60 Cells; Humans; Imatinib Mesylate; Irinotecan; K562 Cells; Leukemia; Lymphoma; Mercaptopurine; Piperazines; Pyrimidines; Time Factors

Topics: Azathioprine; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Lymphoma; Mercaptopurine; Risk Factors

A 66-year-old woman with malignant lymphoma became neutropenic during chemotherapy and developed cryptococcemia. After amphotericin B had been commenced, she developed significant hypokalemia and polyuria, though her renal function remained stable. The laboratory findings showed no evidence of renal tubular acidosis. With vigorous water and potassium replacement, amphotericin B had been continued until the cumulative dose reached 2.5 g. After the cessation of amphotericin B, the hypokalemia and polyuria resolved promptly. Based on theses findings, she was diagnosed as nephrogenic diabetes insipidus with hypokalemia and without renal tubular acidosis due to amphotericin B. This complication is usually reversible, and vigorous water and potassium replacement may allow completion of treatment by amphotericin B, though careful monitoring of body water balance and renal function is of importance.

Topics: Aged; Amphotericin B; Antifungal Agents; Antigens, Fungal; Antimetabolites, Antineoplastic; Bacteremia; Cryptococcosis; Cryptococcus neoformans; Diabetes Insipidus, Nephrogenic; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Lymphoma; Mercaptopurine; Tomography, X-Ray Computed

Topics: Azathioprine; Humans; Inflammatory Bowel Diseases; Lymphoma; Mercaptopurine; Risk Factors

The use of azathioprine and 6-mercaptopurine for inflammatory bowel disease increased in the early 1990s. We sought to determine the effect of this change in therapy on the risk of lymphoma in patients with inflammatory bowel disease.. All patients with inflammatory bowel disease at a single tertiary care medical center who developed lymphoma between 1985-2000 were identified and the pathologic features of the lymphoma including presence of Epstein- Barr virus were determined. The patients were divided into two 8-year periods (1985-1992, 1993-2000) corresponding with the introduction of azathioprine and 6-mercaptopurine in 1993.. Eighteen patients with lymphoma were identified, 6 between 1985-1992 and 12 between 1993-2000. Six of 18 lymphomas occurred in patients treated with azathioprine or 6-mercaptopurine, all between 1993-2000. Seven patients developed Epstein-Barr virus-positive lymphoma (1 from 1985-1992, 6 from 1993-2000). Five of 7 Epstein-Barr virus-positive lymphomas occurred in patients treated with azathioprine or 6-mercaptopurine compared with 1 of 11 Epstein-Barr virus-negative lymphomas (P = 0.01). Approximately 1200 patients with inflammatory bowel disease were treated with these agents between 1993-2000.. Treatment of inflammatory bowel disease with azathioprine or 6-mercaptopurine appears to be associated with a small increased risk of Epstein-Barr virus-positive lymphoma.

Topics: Adult; Aged; Aged, 80 and over; Azathioprine; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Lymphoma; Male; Mercaptopurine; Middle Aged; Risk Factors

The poor absorption of orally administered 6-mercaptopurine (6MP) causes a wide variation in its cytotoxic efficacy. An i.v. dosage form would eliminate this problem. Our objective was to compare the pharmacokinetics of 6MP administered orally with those of an i.v. dosage form 6-mercaptopurine riboside (6MPR), in children with acute lymphoblastic leukemia or malignant lymphoma.. A total of 10 children were treated with oral 6MP, 50 mg/m(2) per day, while five children were treated with 6MPR, 50 mg/m(2) per day, administered by rapid i.v. injection. The plasma concentrations of 6MP and of 6MPR were measured on day 0, while the concentrations of 6-thioguanine nucleotides (6TGN) in red blood cells (RBC) were measured on day 2. The area under the plasma concentration-time curve (AUC1-5) was calculated from 1 to 5 h after drug administration.. With the intravenously administered 6MPR, the AUC1-5 ranged from 124 to 186 (1.5-fold range, median 145) microM min; only two samples were obtained for the RBC concentration of 6TGN, and were 121 and 273 pmol per 25 mg hemoglobin. With the orally administered 6MP, the AUC1-5 ranged from 23 to 65 microM min (2.8-fold range, median 56); the RBC concentration of 6TGN ranged from 18 to 152 pmol per 25 mg hemoglobin (median 75).. The i.v. administration of 6MPR showed less interindividual variation in the AUC1-5 coupled with a higher RBC level of 6TGN as compared with those by oral 6MP. We conclude that the i.v. administration of 6MPR achieves stable blood levels of active drug in children undergoing cancer chemotherapy.

Topics: Administration, Oral; Adolescent; Antimetabolites, Antineoplastic; Area Under Curve; Child; Child, Preschool; Female; Humans; Injections, Intravenous; Lymphoma; Male; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Thioinosine

We conducted a retrospective study of 32 patients with histologically confirmed primary central nervous system lymphoma treated in our institute between 1971 and 1995 with an emphasis on the role of chemotherapy. Thirty of the 32 patients underwent tumor resection, whereas 2 patients had biopsies only. Twenty-eight patients received adjuvant therapy, 9 of whom received radiation therapy alone, 2 received chemotherapy alone, and 17 received both radiation therapy and chemotherapy. Chemotherapies performed were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone). VEMP or VENP (vincristine, cyclophosphamide, mercaptopurine [or Natulan], and prednisolone), intravenous ACNU (nimustine), and intravenous or intra-arterial MCNU (ranimustine) and CBDCA (carboplatin). Survival data were available for 30 of the 32 patients. The median survival time of this study was 12.5 months. Twenty-seven patients died from one month through 79 months after the initiation of therapy, and 3 patients were alive for 13 to 69 months. Two patients who received the combination of radiation therapy and chemotherapy survived longer than 5 years. Although radiation therapy and chemotherapy were individually both effective and prolonged the survival time, their combination was more effective. The median survival time was significantly shorter (7.0 vs 16.5 months, p < 0.05) for the patients who received radiation therapy alone than for the patients who received the combination of radiation therapy and chemotherapy. We conclude from our results and review of previous studies that it is important for the chemotherapy of primary central nervous system lymphoma 1) to apply a combination of a variety of effective drugs, similar to that for systemic malignant lymphoma, and 2) to make a sufficient amount of anti-cancer drugs penetrate the whole central nervous system, thereby satisfying the adequate dose intensity for each drug.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Neoplasms; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Humans; Infusions, Intra-Arterial; Infusions, Intravenous; Lymphoma; Male; Mercaptopurine; Middle Aged; Nimustine; Prednisolone; Prednisone; Procarbazine; Survival Rate; Vincristine

Topics: Azathioprine; Colitis, Ulcerative; Crohn Disease; Cyclosporine; Humans; Immunosuppressive Agents; Intestinal Neoplasms; Lymphoma; Mercaptopurine; Risk Factors

Sixteen children with refractory hematological malignancies were treated with a combination of BH.AC, aclacinomycin-A, 6-MP and predonisolone (BH-AC.AMP protocol). They were ALL(6), ANLL(8), CML(1) and NHL(1). The CR ratio was 17% in ALL, 50% in ANLL, and blast crisis of CML was treated successfully but NHL failed in the induction remission. Major complications were vomiting, nausea, gastrointestinal bleeding, hematuria and hemorrhagic cystitis. More than 10 days or 120 mg/m2 administration of aclacinomycin-A was thought to induce more severe side effects.

Topics: Aclarubicin; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cytarabine; Drug Administration Schedule; Female; Humans; Infant; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Lymphoma; Male; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Remission Induction

Twenty-two cases of primary gastric lymphoma have been clinicopathologically reviewed and factors influences the prognosis were examined. An increased tumor size of more than 10 cm, an increased tumoral penetration, a lymph node involvement, and stage IV classification decreased the survival rates. All patients given stage I classification have remained alive without having received chemotherapy. The survivors of stages III & IV amounted to only three patients who were treated by surgery and systemic chemotherapy. A radical operation is the choice of treatment for a gastric lymphoma but aggressive chemotherapy should be supplemented for advanced cases.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Humans; Lymphatic Metastasis; Lymphoma; Male; Mercaptopurine; Middle Aged; Neoplasm Invasiveness; Prednisone; Procarbazine; Prognosis; Stomach Neoplasms; Vincristine

A sensitive and rapid assay for the quantitation of thioinosine monophosphate and thioguanosine monophosphate, the major intracellular active metabolites of mercaptopurine and thioguanine, respectively, has been developed. Neoplastic cells are extracted with trichloracetic acid, and the neutralized acid extracts are analyzed by ion-pairing high-performance liquid chromatography with dual-channel uv-wavelength detection. This technique provides a lower limit of sensitivity of 30 pmol of thioinosine monophosphate and 10 pmol of thioguanosine monophosphate. The number of cells assayed per sample was 2 X 10(7). This assay makes it possible to detect and quantitate low levels of thioinosine monophosphate and thioguanosine monophosphate present in neoplastic cells obtained directly from patients receiving mercaptopurine or thioguanine chemotherapy.

Topics: Bone Marrow; Cell Line; Chromatography, High Pressure Liquid; Guanine Nucleotides; Humans; Inosine Monophosphate; Inosine Nucleotides; Leukemia, Myeloid, Acute; Lymphoma; Mercaptopurine; Thioguanine; Thionucleotides

The concentrations of 6-mercaptopurine were studied in plasma and red blood cells from 10 children with acute leukaemia or non-Hodgkin lymphoma receiving oral maintenance therapy. The doses varied between 25 and 79 mg/m2 body surface once daily. Large interindividual differences were found in the concentrations both in plasma and in red blood cells. There was no clear relationship between the dose administered and the concentrations obtained. However, in each patient the concentrations in plasma and in red blood cells were very similar. In most patients, the peak concentrations were reached 1-2 hours after dose intake and the concentrations then declined with half-lives less than 1 hour. Further studies are necessary to evaluate the potential value of drug level monitoring in optimizing treatment with oral 6-mercaptopurine.

Topics: Acute Disease; Administration, Oral; Adolescent; Child; Child, Preschool; Erythrocytes; Female; Humans; Kinetics; Leukemia; Lymphoma; Male; Mercaptopurine

The effect of repeated courses of chemotherapy on gastrointestinal tumors seen in a 43 year-old male patient with multiple lymphomatous polyposis involving the entire gastrointestinal tract was presented. Numerous polypoid lesions from the stomach to the rectum were the characteristic finding in this case. The biopsied specimens from polyps either of the stomach or large intestine showed diffuse lymphocytic accumulation in the submucosa, which is consistent with multiple lymphomatous polyposis of the gastrointestinal tract. Remarkable regression of the large masses in the gastrointestinal tract was obtained by two courses of VEMP therapy, along with improvement of hypoalbuminemia and a positive CRP. Recurrence of gastrointestinal masses in the cecum and rectum was also eliminated by six courses of CHOP therapy, and a total of nine courses of CHOP therapy led to complete disappearance of masses in the gastrointestinal tract. The present case is different from the others in terms of the following viewpoints that first the ensuing large masses favorably responded to repetitive chemotherapy, secondly the histopathological findings remained benign despite the fact that large nodular masses had recurred in the cecum and rectum, and thirdly the pathological changes were still confined to the gastrointestinal tract without developing systemic malignant manifestations.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Gastrointestinal Neoplasms; Humans; Intestinal Polyps; Lymphoma; Male; Mercaptopurine; Prednisolone; Prednisone; Vincristine

Dogs with malignant lymphoma were given chemotherapy consisting of nitrogen mustard, vincristine sulfate, prednisone, L-asparaginase, and 6-mercaptopurine (MOPA-6) for 14 days. Among 62 dogs that completed treatment with MOPA-6, 47 (76%) had complete remission, and 13 (21%) had partial remission and 2 had no response to chemotherapy. Twenty-two of the 62 dogs were not returned by their owners for additional therapy and died 15 to 391 (median 21) days after MOPA-6 from infections or recurrent disease. A median of 1 month after starting MOPA-6 therapy, 40 dogs (35 in complete remission, 5 in partial remission) were given total body irradiation (TBI), followed by infusion of fresh autologous marrow. Twenty dogs were given 13.5 Gray (Gy) of TBI at 4 centi-Gray (cGy)/min. Among 16 evaluable dogs, 7 had recurrence of lymphoma at a median of 169 days. Two dogs died with veno-occlusive disease of the liver, 3 with pneumonia, 3 with hemorrhage, and 1 was killed. Twenty dogs were given 11.8 to 14.7 Gy of TBI at 2 cGy/min. Among 14 evaluable dogs, 9 had recurrence of lymphoma at a median of 117 days. The remaining 5 dogs were killed at 110 to 680 days; lymphoma was not present at necropsy. The results indicated that doses of TBI of 11.8 to 14.7 Gy did not reduce the recurrence of lymphoma, compared with results obtained in a previous study with 8.4 Gy of TBI. Furthermore, increased doses of TBI increased acute and delayed toxicities. Alternatively, recurrent disease may have been due to lymphoma cells contained in the infused remission marrow.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Bone Marrow Transplantation; Combined Modality Therapy; Dog Diseases; Dogs; Dose-Response Relationship, Radiation; Lymphoma; Mechlorethamine; Mercaptopurine; Neoplasm Staging; Prednisolone; Transplantation, Autologous; Vincristine; Whole-Body Irradiation

Of those patients with localized (CS I-II) non-Hodgkin's lymphoma of Waldeyer's ring who were treated with radiotherapy or radiotherapy plus chemotherapy and who suffered relapses at the National Cancer Center Hospital over the past 22 years, 24 cases were analyzed on the basis of their response rate and duration of remission with reinduction chemotherapy, and survival time after recurrence. The group [ADM (+)], treated with regimens including adriamycin, was compared with the group [ADM (-)] treated with regimens excluding adriamycin. Complete response was seen in 9 out of 11 cases (81.8%) and in 8 out of 13 cases (61.5%) for the ADM (+) group and the ADM (-) group, respectively (p greater than 0.1). The period of complete response of the ADM (+) and ADM (-) groups was compared using the logrank method. The prognosis of the former was significantly (p less than 0.01) better than that of the latter and the median duration of remission was 30 months and 7 months, respectively. When the survival after recurrence of the ADM (+) and ADM (-) groups was compared, the median survival time was 38 months for the ADM (+) group and 12 months for the ADM (-) group, but no significant difference was observed between the two groups (0.05 less than p less than 0.1).

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Female; Head and Neck Neoplasms; Humans; Lymphatic Metastasis; Lymphoma; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Retrospective Studies; Vincristine

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Drug Therapy, Combination; Humans; Lung Diseases; Lymphoma; Male; Mercaptopurine; Nocardia Infections; Prednisolone; Sulfamethoxazole; Trimethoprim; Vincristine

A 28-year-old man developed AML 18 months after a diagnosis of non-Hodgkin's lymphoma, diffuse small cell type, clinical stage IIA. Induction therapy for the lymphoma consisted 60Co 4000 rads bilaterally to the cervical areas and 2000 rads to the right cervical area. Complete remission was attained. Nineteen courses of combination chemotherapy with Vincristine (VCR), 6-meraptopurine (6 MP), cyclophosphamide (CY) and predonisolone (pred) was added (Total dose: VCR; 26.5 mg, 6 MP; 3320 mg, CY; 3350 mg, pred; 4310 mg). Seven days after the final chemotherapeutic treatment he developed AML with DIC. Leukemic cells were peroxidase and specific esterase (naphthol AS-D chloroacetate) positive. Induction therapy for the AML consisting of DCMP (Daunomycin, Cytosine arabinosid, 6 MP and pred) and VCR (vindesine, CY and pred) was unsuccessful. The patient died of cranial hemorrhage 3 month after the diagnosis of acute leukemia. Autopsy revealed no recurrence of non-Hodgkin's lymphoma in the lymph nodes, bone marrow, spleen and liver. Seven other cases reported in the Japanese literature are reviewed.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Disseminated Intravascular Coagulation; Drug Administration Schedule; Humans; Leukemia, Myeloid, Acute; Lymphoma; Male; Mercaptopurine; Prednisolone; Radiotherapy Dosage; Vincristine

6-Mercaptopurine was found to inhibit the growth of cultured human lymphoma P3HR-1 cells and the incorporation of [3H]-uridine into trichloroacetic acid-precipitable materials of the cells. One of the derivatives of 6-mercaptopurine, 6-mercaptopurine ribonucleoside triphosphate (6-thio-ITP), was found to inhibit in vitro RNA synthesis (both engaged and free enzyme activities) of the isolated nuclei from P3HR-1 cells. The alpha-amanitin-resistant RNA polymerase (polymerase I) and alpha-amanitin-sensitive RNA polymerase (polymerase II) of the cells were isolated and partially purified by either diethylaminoethyl cellulose or diethylaminoethyl Sephadex column chromatography, followed by DNA-cellulose affinity chromatography. It was found that these partially purified enzymes were also sensitive to 6-thio-ITP inhibition. Kinetic studies showed that the inhibition of RNA polymerase activities by 6-thio-ITP could be reversed by increasing concentrations of guanosine 5'-triphosphate in the reaction mixture, indicating that 6-thio-ITP may act as a competitive inhibitor of the enzymes by competing with guanosine 5'-triphosphate for its enzyme-binding site. These data suggest that inhibition of RNA transcription by 6-thio-ITP may be considered as one of the mechanisms of the cytotoxic action of 6-mercaptopurine in human tumor cells.

Topics: Cell Line; Cell Survival; DNA-Directed RNA Polymerases; Humans; Lymphoma; Mercaptopurine; RNA Polymerase I; RNA Polymerase II; Thionucleotides

A 65-year-old male visited the Sawara Hospital with the chief complaint of right intrascrotal mass. The mass without tenderness, in which right testis and spermatic cord appeared to be involved, reached the right inguinal region. Right high orchiectomy was performed under the diagnosis of a testicular tumor. Histological diagnosis was malignant lymphoma. Intravenous pyelogram revealed right hydronephrosis and 67Ga-scintigram showed an abnormal accumulation of radioisotopes in the pelvic and paraaortic region. Chemotherapy with vincristine, cyclophosphamide, 6-mercaptopurine and prednisolone was performed under the diagnosis of stage IV lymphoma. Two months after chemotherapy, right hydronephrosis disappeared and no abnormal accumulation in 67Ga-scintigram was found. He has been doing well three months after treatment.

Topics: Aged; Castration; Cyclophosphamide; Gallium Radioisotopes; Humans; Lymphoma; Male; Mercaptopurine; Prednisolone; Testicular Neoplasms; Vincristine

A series of 2'-O-acyl derivatives of 6-thioinosine cyclic 3',5'-phosphate (6-HS-cRMP) were prepared and examined for their cytotoxic effects on S49 mouse lymphoma cells which were deficient in hypoxanthine-guanine phosphoribosyltransferase (HGPRTase). Cytotoxicity increased with the lipophilicity of the acyl group to a lowest EC50 of 65 micrometer for the 2'-O-palmityl derivative. Addition of a mutation in the gene for cAMP-dependent protein kinase to the HGPRTase-deficient cell line confers resistance to 2'-O-butyryl-cAMP but not to 2'-O-butyryl-6-HS-cRMP, indicating that the latter does not exert its toxic effect via activation of protein kinase. The time course of cell kill by 2'-O-palmityl-6-HS-cRMP resembled that of 6-mercaptopurine and not that of cyclic AMP in these cells. The data suggest that the intact cyclic nucleotides are penetrating the cells and being converted, by phosphodiesterase action and deacylation, to the first toxic metabolite of 6-mercaptopurine, thioinosinic acid.

Topics: Animals; Antineoplastic Agents; Cyclic AMP; Drug Resistance; Hypoxanthine Phosphoribosyltransferase; Inosine; Lymphoma; Mice; Neoplasms, Experimental; Nucleotides, Cyclic; Thioinosine; Thionucleotides; Time Factors

Topics: Animals; Antineoplastic Agents; Asparaginase; Bone Marrow Transplantation; Cyclophosphamide; Dogs; Drug Therapy, Combination; Lymphoma; Mechlorethamine; Mercaptopurine; Prednisone; Radiation Chimera; Time Factors; Transplantation, Autologous; Vincristine

From 1964-1975 43 children with non-Hodgkin's lymphoma (NHL) were treated. 60% of the patients had far advanced disease at diagnosis. Therapy before 1970 consisted of low dose irradiation to the primary and single agent chemotherapy; no C.N.S. irradiation to prevent meningeal recurrence was given. Median survival in this group was 5 months; all patients died. Since 1970 all children with NHL were entered into a modified leukaemia protocol regardless of stage or primary site. Therapy comprised an aggressive multiple drug combination, high dose local irradiation and prophylactic C.N.S. irradiation with intrathecal methotrexate. 41% of the patients treated since 1970 survive in continuous complete remission with a median observation time of 31+ (1-93+) months. All relapses occurred within 30 months after diagnosis. Stage of disease was the most important prognostic factor in our patients. Risk of a primary C.N.S. relapse in the total group was 30% for patients without prophylactic C.N.S. therapy compared to only 6% for patients with treatment.

Topics: Adolescent; Age Factors; Child; Child, Preschool; Cyclophosphamide; Female; Humans; Lymphoma; Male; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Remission, Spontaneous; Vincristine

Topics: Asparaginase; Child; Cyclophosphamide; Cytosine; Daunorubicin; Doxorubicin; Drug Therapy, Combination; Hodgkin Disease; Humans; Infant; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma; Melphalan; Mercaptopurine; Methotrexate; Neoplasms; Nitrogen Mustard Compounds; Osteosarcoma; Prednisone; Procarbazine; Prognosis; Remission, Spontaneous; Rhabdomyosarcoma; Teniposide; Thioguanine; Vincristine; Wilms Tumor

Eighty-six children with non-Hodgkin's lymphoma were studied from 1964 to January 31, 1975. Seventy-six percent of the 43 patients in the nonprotocol group had far advanced disease, and 76% had Rappaport's diffuse histology. Only 11% of these patients survived free of disease. The second group of 43 patients received the LSA2L2 protocol. Seventy-six percent had advanced disease and 86% diffuse histology. Of these patients 76% are surviving free of disease with a median observation time of 25+ months. Fifty-one percent of the survivors are off therapy and without evidence of disease. Prognostic factors such as primary sites, stages, histology, and others are discussed. The most important prognostic factor is early and aggressive therapy, and the achievement of a complete response status within 1-2 months from onset of therapy.

Topics: Adolescent; Antineoplastic Agents; Asparaginase; Carmustine; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Dactinomycin; Daunorubicin; Drug Therapy, Combination; Female; Humans; Hydroxyurea; Lymphoma; Male; Mercaptopurine; Methotrexate; Neoplasm Metastasis; Prednisone; Thioguanine; Vinblastine; Vincristine

Topics: Abdominal Neoplasms; Adolescent; Adult; Cyclophosphamide; Doxorubicin; Female; Humans; Lymphoma; Male; Mercaptopurine; Middle Aged; Prednisolone; Ultrasonography; Vincristine

Topics: Allopurinol; Drug Synergism; Humans; Leukemia; Lymphoma; Mercaptopurine; Thiouridine

Topics: Amides; Animals; Antineoplastic Agents; Azacitidine; Cyclic P-Oxides; Cyclophosphamide; Cytarabine; Disease Models, Animal; Drug Combinations; Female; Imidazoles; Lymphoma; Male; Mercaptopurine; Methotrexate; Mice; Mice, Inbred Strains; Oxazines; Prednisone; Remission, Spontaneous; Time Factors; Triazenes; Vincristine

Topics: Age Factors; Animals; Animals, Newborn; Antilymphocyte Serum; Cricetinae; Cyclophosphamide; Dactinomycin; Female; Immune Sera; Immunization, Passive; Leukemia, Lymphoid; Lymphocyte Transfusion; Lymphoma; Maternal-Fetal Exchange; Mercaptopurine; Methotrexate; Neoplasm Transplantation; Neoplasms, Experimental; Prednisone; Pregnancy; Spleen; Time Factors; Vincristine

Topics: Adenosine; Animals; Ascitic Fluid; Aza Compounds; Biological Transport; Bromodeoxyuridine; Carbon Isotopes; Cell Division; Cell-Free System; Cells, Cultured; Guanosine; Inosine; Lymphoma; Male; Mercaptopurine; Methotrexate; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Pyrazoles; Pyrimidinones; Pyrroles; Ribonucleosides; Thymidine; Time Factors; Transplantation, Homologous

Topics: Animals; Carcinoma, Ehrlich Tumor; Cell Division; Cells, Cultured; Depression, Chemical; Female; In Vitro Techniques; Lymphoma; Mercaptopurine; Mice; Mice, Inbred Strains; Time Factors

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: Animals; Antimetabolites; Carbon Isotopes; Carcinoma, Ehrlich Tumor; Chromatography; Diphosphates; Drug Synergism; Lymphoma; Male; Mercaptopurine; Mice; Neoplasms, Experimental; Nucleosides; Nucleotides; Pentosephosphates; Ribose

Topics: Alkaline Phosphatase; Animals; Benz(a)Anthracenes; Duodenum; Electrophoresis, Disc; Embryo, Mammalian; Enzyme Repression; Hot Temperature; Hydrogen-Ion Concentration; Liver; Lymphoma; Mercaptopurine; Mice; Oncogenic Viruses; Spleen; Thymus Gland; Thymus Neoplasms; Urethane

Topics: Aminopterin; Child; Child, Preschool; Diagnosis, Differential; Haptoglobins; Hematologic Diseases; Humans; Infant; Infections; Leukemia; Lymphoma; Mercaptopurine; Neuroblastoma; Prednisone

Topics: Animals; Drug Synergism; Lymphoma; Mercaptopurine; Mice; Neoplasms, Experimental; Nucleosides; Time Factors

Topics: AKR murine leukemia virus; Animals; Antilymphocyte Serum; Azathioprine; Hemagglutination; Immune Sera; Injections, Intraperitoneal; Lymphocytes; Lymphoma; Mercaptopurine; Mice; Neoplasms, Experimental; Rabbits; Thymus Gland

Topics: Adult; Blood Cell Count; Bone Marrow Examination; Brain Neoplasms; Carotid Arteries; Cobalt Isotopes; Craniotomy; Electroencephalography; Humans; Intracranial Pressure; Leukemia, Myeloid; Lymphoma; Male; Mercaptopurine; Methotrexate; Microscopy, Phase-Contrast; Prednisolone; Radiography

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Biopsy; Blood Protein Electrophoresis; Blood Sedimentation; Blood Transfusion; Busulfan; Congo; Female; gamma-Globulins; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma; Male; Mercaptopurine; Middle Aged; Prednisone

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

Topics: Adrenal Cortex Hormones; Alkylating Agents; Child; Cyclophosphamide; Drug Therapy; Herpes Zoster; Hodgkin Disease; Leukemia; Lymphoma; Mechlorethamine; Mercaptopurine; Methotrexate; Neoplasms; Prednisolone; Surgical Procedures, Operative; Thrombocytopenia

Topics: Antineoplastic Agents; Child; Chlorambucil; Cyclophosphamide; Drug Therapy; Ganglioneuroma; Gastrointestinal Diseases; Hodgkin Disease; Leukemia; Leukemia, Myeloid; Liver Neoplasms; Lymphoma; Mechlorethamine; Mercaptopurine; Methotrexate; Neoplasms; Pathology; Radiation Injuries; Stomach; Toxicology; Vinblastine; Vincristine; Wilms Tumor

Topics: Bone Marrow Examination; Drug Therapy; Eosinophilic Granuloma; Lymphoma; Mechlorethamine; Mercaptopurine; Neoplasms; Pathology; Prednisone

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

Topics: Animals; Bone Marrow Transplantation; Hematopoietic System; Leukemia; Leukemia, Experimental; Leukemia, Myeloid; Lymphoma; Mercaptopurine; Mice; Neoplasms; Neoplasms, Experimental; Organotherapy; Pharmacology; Research

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; Cortisone; Cyclophosphamide; Folic Acid Antagonists; Hemostasis; Infections; Leukemia; Leukemia, Experimental; Lymphoma; Mercaptopurine; Mice; Penicillins; Rats; Research

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: Animals; Anti-Bacterial Agents; Antibodies; Antineoplastic Agents; Blood Cells; Carcinoma, Ehrlich Tumor; Cortisone; Cytarabine; Cytosine; Leukemia L1210; Leukemia, Experimental; Lymphoma; Mercaptopurine; Methotrexate; Mice; Neoplasms; Neoplasms, Experimental; Pharmacology; Research; Sarcoma 180

Topics: Biopsy; Bone Marrow Cells; Carcinoma; Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Lymphoma; Mercaptopurine; Multiple Myeloma; Myositis; Neoplasms; Polymyositis; Prednisone; Sarcoma

Topics: Adrenal Cortex Hormones; Agammaglobulinemia; Anemia; Anemia, Hemolytic; Autoimmune Diseases; Blood Protein Disorders; gamma-Globulins; Humans; Leukemia; Lymphoma; Mercaptopurine; Nitrogen Mustard Compounds; Waldenstrom Macroglobulinemia

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: Antineoplastic Agents; Azaguanine; Cortisone; Cyclophosphamide; Humans; Lymphoma; Mercaptopurine; Mitomycin; Mitomycins; Nitrogen Mustard Compounds; Prednisolone; Thiotepa; Triethylenemelamine

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

Current trends in the search for chemical compounds having an inhibitory action on the growth of malignant cells are reviewed in this article. Several agents are sufficiently promising that clinical trials with them are in progress. One of these, an aromatic nitrogen mustard (C.B. 1348), appears to be useful as an adjunctive therapeutic measure in patients with malignant lymphoma, chronic lymphocytic leukemia, and mycosis fungoides who have become refractory to other methods of treatment. The introduction of certain purine antagonists, of which 6-mercaptopurine has been given the most extensive clinical trial, has opened up a new field of experimental and clinical investigation. 6-mercaptopurine and related compounds appear to be particularly useful in the treatment of acute leukemia in adults, but they are also useful, together with the folic acid antagonists and the steroid hormones, in the management of acute leukemia in children. While at present chemotherapeutic agents currently under investigation rarely cause significant regression of inoperable primary or metastatic solid tumors, the possibility of eventual more effective control in many types of malignant disease is not as dismal as it was a decade ago.

Topics: Adult; Antineoplastic Agents; Humans; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma; Mercaptopurine; Mycosis Fungoides; Neoplasms

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