levoleucovorin and Burkitt-Lymphoma

Burkitt lymphoma is a unique B-cell malignancy with a high proliferation rate and characteristic genetic changes involving the c-myc oncogene. Burkitt lymphoma is common in children but also occurs in adults, where distinction from diffuse large B-cell lymphoma may pose a problem. The development of brief, very intensive chemotherapy regimens has led to a very high cure rate in children with Burkitt lymphoma. The use of these regimens in adults, often in combination with the antibody rituximab (Rituxan), has also made the cure of a majority of adults possible. Burkitt lymphoma in adults cannot be treated effectively with the common regimens used for diffuse large B-cell lymphoma such as CHOP-R (cyclophosphamide, doxorubicin HCl, vincristine [Oncovin], prednisone, rituximab). Prompt diagnosis and initiation of appropriate therapy with attention to the possibility of tumor lysis syndrome are necessary for optimal results.

Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Clinical Trials, Phase II as Topic; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Genes, myc; Humans; Ifosfamide; Leucovorin; Methotrexate; Practice Guidelines as Topic; Prednisone; Prognosis; Rituximab; Stem Cell Transplantation; Survival Analysis; Teniposide; Treatment Outcome; Vincristine

Burkitt's lymphoma (BL) and Burkitt-like acute lymphoblastic leukemia (ALL) are uncommon lymphoproliferative disorders after solid organ or stem cell transplantation. Although their prognosis is considered to be poor, there are scarce data on the clinical characteristics and the response to specific therapies. We report the main clinical characteristics and the results of a specific intensive chemotherapy in 5 adult patients with postransplant BL/ALL3 included in the PETHEMA ALL3/97 protocol. Two patients died in induction, another died in consolidation phase and the remaining 2 patients are in continuous complete remission 6 and 18 months from the diagnosis.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Cyclophosphamide; Cytarabine; Dexamethasone; Epstein-Barr Virus Infections; Etoposide; Female; Heart Transplantation; Humans; Ifosfamide; Immunosuppression Therapy; Kidney Transplantation; Leucovorin; Liver Transplantation; Male; Methotrexate; Middle Aged; Peripheral Blood Stem Cell Transplantation; Postoperative Complications; Prednisone; Remission Induction; Retrospective Studies; Transplantation; Treatment Outcome; Vincristine

Burkitt's lymphoma and small noncleaved Burkitt's-like lymphoma are rare and are highly aggressive forms of non-Hodgkin's lymphoma that are characterized by dysregulation of the c-myc oncogene. Patients with human immunodeficiency virus (HIV) also appear to be at risk for developing Burkitt's lymphomas. Treatment options for Burkitt's lymphoma involve complex chemotherapy regimens that contain as many as 10 cytotoxic agents. Approximately 50%-80% of adult patients with Burkitt's lymphoma or small, noncleaved lymphoma can be cured with these intensive chemotherapy regimens, and in pediatric populations, the cure rate is even higher. However, a number of factors often compromise the outcome of patients with Burkitt's lymphoma. For instance, the high proliferation rate of Burkitt's lymphoma enhances the risk for tumor lysis syndrome, which results from metabolic imbalances, such as hyperuricemia, that occur as large numbers of malignant cells are lysed during cytotoxic chemotherapy. Standard treatment for tumor lysis syndrome includes adjustments in the chemotherapy regimen, vigorous hydration, administration of a uric acid synthesis inhibitor like allopurinol, and alkalinization. The administration of recombinant urate oxidase (rasburicase) also has been shown to provide effective prophylaxis against hyperuricemia in pediatric and adult patients with hematologic malignancies. The lifetime risk of developing central nervous system disease is 20%-30% for Burkitt's lymphoma. Consequently all chemotherapy regimens with activity in Burkitt's lymphoma utilize some form of central nervous system prophylaxis, such as systemic or intrathecal methotrexate or cytarabine. In the past, patients with HIV who developed Burkitt's lymphoma often received inadequate chemotherapy doses because of their immunosuppression. With the discovery of highly active antiretroviral therapy, the ability to treat and control Burkitt's lymphoma in patients with HIV has improved.

Topics: Adult; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; Bleomycin; Burkitt Lymphoma; Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Enzyme Inhibitors; Etoposide; HIV Infections; Humans; Ifosfamide; Leucovorin; Methotrexate; Time Factors; Treatment Outcome; Urate Oxidase; Vincristine

Topics: Adult; Aged; Antineoplastic Agents; Bone Marrow; Burkitt Lymphoma; Child; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Leucovorin; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Prognosis; Remission, Spontaneous; Time Factors

We conducted a phase II study to evaluate in 72 adult patients the efficacy of the intensive LMB chemotherapy regimen, previously reported by the Société Française d'Oncologie Pédiatrique for children with Burkitt lymphoma and L3 acute lymphoblastic leukemia.. Treatment began with a prephase (low-dose steroids, vincristine and cyclophosphamide), except in patients with low tumor burden. Group A (resected stage I and abdominal stage II disease) received three courses of vincristine, cyclophosphamide, doxorubicin and prednisone. Group B (not eligible for groups A or C) received five courses of chemotherapy comprising high-dose methotrexate, infusional cytarabine and intrathecal (IT) methotrexate. Group C (patients with central nervous system and/or bone marrow involvement with < 30% of blast cells) received eight courses containing intensified high-dose methotrexate, high-dose cytarabine, etoposide and triple IT injections.. The 2 year event-free survival and overall survival rates for the 72 patients were 65% and 70%, respectively. Age > or = 33 years and high lactate dehydrogenase value were associated with a shorter survival. No response to COP was also associated with a poor outcome in group B.. Patients with advanced-stage Burkitt lymphoma, including those with bone marrow and/or central nervous system involvement, can be cured with a short-term intensive chemotherapy regime tailored to the tumor burden.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Cyclophosphamide; Cytarabine; Disease-Free Survival; Doxorubicin; Etoposide; Female; Humans; Hydrocortisone; Leucovorin; Male; Methotrexate; Middle Aged; Neoplasm Staging; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Prognosis; Prospective Studies; Survival Rate; Vincristine

Burkitt and Burkitt-like lymphomas are rapidly growing tumors which require specialized therapy. Although intensive, multi-agent regimens have been effective in children, results are more variable in adults. Magrath et al. previously described a regimen that was highly effective in children and young adults. This phase II study of a modified Magrath regimen was designed to assess its efficacy in older adults and reduce treatment-related toxicity. Fourteen patients with Burkitt/Burkitt-like lymphoma and median age of 47 years were stratified into two categories: low-risk (normal LDH and a single focus of disease measuring less than 10 cm, 3 patients) and high risk (all other, 11 patients). Low-risk patients received three cycles of modified CODOX-M (cyclophosphamide, doxorubicin, adriamycin, vincristine with intrathecal methotrexate and cytarabine followed by high-dose systemic methotrexate, regimen A). High-risk patients received four alternating cycles of regimens A and B (A-B-A-B). Regimen B consisted of ifosfamide, cytarabine, etoposide and intrathecal methotrexate (IVAC). The modified treatment regimen was associated with no grade 3/4 neuropathy and only one episode of grade 3/4 mucositis. All patients completed protocol therapy and there were no treatment-related deaths. Twelve patients (86%, 90% CI: 61 97%) achieved a complete response; 1 patient achieved a PR and 1 patient died of progressive disease. Nine patients (64%) are alive and disease free at a median follow-up of 29 months. This modified Magrath regimen is effective and well-tolerated in a representative group of older adult patients.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Cyclophosphamide; Cytarabine; Doxorubicin; Etoposide; Granulocyte Colony-Stimulating Factor; Humans; Ifosfamide; Leucovorin; Mesna; Methotrexate; Middle Aged; Survival Analysis; Treatment Outcome; Vincristine

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

To develop antimetabolite-based consolidation regimens that minimize acute and long-term toxicities and improve the survival rate of children with standard-risk B-lineage acute lymphocytic leukemia (ALL).. Seven hundred twenty-seven eligible patients with standard-risk early pre-B ALL were registered onto the study. Seven hundred sixteen patients attained a complete remission (CR) after induction therapy. Of these, 114 patients were randomized to a different regimen and were the subject of a separate report. Six hundred two patients were randomized to receive one the following regimens: intermediate-dose methotrexate (IDMTX) with leucovorin rescue on weeks 7, 10, 13, 16, 19, and 22 (regimen A); regimen A plus asparaginase (ASP) administered intramuscularly (i.m.) weekly for 24 weeks (regimen B); or regimen A plus a 24-hour infusion of cytarabine (AraC) with each IDMTX (regimen C). After consolidation, patients were placed on maintenance therapy through week 156. Regimens A and C were opened in February 1986, and regimen B in May 1987. Comparisons are based on concurrently randomized patients (May 1987 to January 1991 between regimens A and B, and February 1986 to January 1991 between regimens A and C).. The 5-year continuous CR (CCR) rates were not significantly different: A versus B, 78.1% (3.9 +/- SE) versus 83.3% +/- 3.5% and A versus C, 79.4% +/- 3.2% versus 83.5% +/- 2.9%; P by one-sided log-rank tests were .27 and .34, respectively. Significant treatment differences were not found with regard to sex, rate of testicular and CNS relapse, or CNS complications. During consolidation, regimen C had significantly more bacterial infections (P = .0032) and days spent in the hospital (P < .001) compared with regimen A.. We were unable to show a statistical advantage of adding either ASP or AraC to IDMTX in terms of improvement in event-free survival (EFS).

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Burkitt Lymphoma; Child, Preschool; Cytarabine; Female; Humans; Leucovorin; Male; Methotrexate; Recurrence; Remission Induction

Advanced Burkitt's lymphoma (BL) has an extremely poor prognosis in adults. With a previous protocol including CNS prophylaxis, 40% of our adult patients achieved CR and only 13% became long survivors. In 1988, following this poor experience, we adopted a very intensive pediatric-derived protocol.. Twenty-one consecutive patients, 8 adults (median age 35, stage III: 1; IV: 7; leukemias: 6) and 13 children (median age 10, state III: 8; IV: 5; leukemias: 4) were treated with the same protocol (POG 8617), based on alternate two-phase cycles with sequential high-dose CTX, VCR, ADM + CNS chemoprophylaxis (phase A) and HD MTX + HiDAC (phase B). Adults received 6 cycles, children 8; i.t. prophylaxis in phase B was omitted in adults.. Twenty of 21 (95%) patients achieved CR (adults 100%, children 92%). Two patients died early; 2 relapsed at 4 and 9 months. With a median follow-up of 28 months (4-96), 17 patients (81%) are event free (adults 75%, children 85%). Severe infections affected 62% of adults and 15% of children.. (1) The prognosis of adult advanced BL definitely improved with this intensive protocol. (2) There were no differences in outcome between adults and children. (3) Outcome of lymphoma and leukemia was similar. (4) Severe infections occurred frequently in adults. This intensive pediatric protocol requires a careful supportive therapy.

Topics: Adolescent; Adult; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Treatment Outcome; Vincristine

Type and duration of treatment for highly aggressive non-Hodgkin's lymphoma has been a matter of debate over the past decade. To determine the therapeutic efficacy of an abbreviated treatment regimen, 26 patients with newly-diagnosed highly aggressive lymphomas, 17 of them belonging to the International Working Formulation (IWF) group I and 9 with Burkitt's lymphoma (IWF J), were entered in a study using short-term weekly chemotherapy followed by high-dose therapy and autologous bone marrow transplantation.. Besides histology, requirements for entry into to the study were age between 16 and 60 years, stage 1 bulky disease and elevated LDH or stage II to IV disease with or without bulk or elevated LDH, and an absence of HIV infection or CNS involvement at diagnosis. The treatment plan was 12 weeks of MACOP-B or VACOP-B chemotherapy followed by high dose therapy and autologous bone marrow transplantation in first complete remission.. Twenty patients (76%), 16 (62%) of those on MACOP-B or VACOP-B, 1 who had received 2 cycles of ProMACE-CytaBOM prior to MACOP-B and 3 after a first salvage regimen, achieved complete remissions. Seventeen patients (65%) were transplanted in first remission, and 15 (58%) after induction treatment with only MACOP-B or VACOP-B. Reasons for not being given high dose therapy and autologous bone marrow transplantation (ABMT) were failure to achieve complete remission in 6 patients, early relapse in 2 and severe pulmonary toxicity associated with chemotherapy in 1. The median time of follow-up was 45 months. At 3 years, the estimated event-free survival was 31% (CI 14%-50%) and the overall survival 48% (CI 25%-67%). There were no deaths from toxic effects of treatment. Pretreatment factors associated with relapse were stage III or IV disease, age over 30 years and bone marrow involvement. Logrank analysis showed that age was the only factor significantly associated with poor event-free survival.. Short-term weekly chemotherapy followed by high-dose therapy with the CBV regimen in first remission is not a higly effective treatment for advanced lymphoblastic and Burkitt's lymphomas. The 30% rate of failure to achieve partial remission after 6 weeks and/or complete response after 12 weeks of MACOP-B or VACOP-B treatment, as well as the 42% failure rate to undergo ABMT in first remission, suggest that more aggressive chemotherapy should be used in the beginning.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Transplantation; Burkitt Lymphoma; Carmustine; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Etoposide; Female; Follow-Up Studies; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Remission Induction; Survival Rate; Transplantation, Autologous; Vincristine

Topics: Adult; Aged; Antineoplastic Agents; Bone Marrow; Burkitt Lymphoma; Child; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Leucovorin; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Prognosis; Remission, Spontaneous; Time Factors

To explore the clinical and prognostic features as well as treatment response of childhood B-cell non-Hodgkin's lymphoma/acute lymphoblastic leukemia (B-NHL/B-ALL), so as to better modify the treatment for further improving the prognosis.. The clinical data of 43 patients with newly-diagnosed childhood B-NHL/B-ALL from July 2005 to December 2013 in West China Second Hospital of Sichuan University were retrospectively analyzed with particular focus on clinical presentations, laboratory findings and histology. Among them 26 patients received B-NHL-2010 protocol and 17 patients received LMB-89 protocol treatment. Kaplan-Meier method was used to compare the survival rates between groups, while multiple factor logistic regression was used to identify the prognostic factors.. (1) The median age at diagnosis was 7.58 (2.42-13.67) years. The male-to-female ratio was 2.9 : 1. No significant difference was found in the median age at diagnosis between male and female children with B-NHL/B-ALL (P = 0.837). (2) Burkitt's lymphoma was the most common (34/43, 79.07%), followed by diffuse large B cell lymphoma (4/43, 9.3%), ALL-L3 (3/43, 6.98%) and others (2/43, 4.65%) in decreasing frequency. (3) According to St. Jude staging classification, 4 patients (9.30%) were divided into stage I, 9 patients (20.93%) into stage II, 23 patients (53.49%) into stage III and 7 patients (16.28%) into stage IV; (4) Clinically, the common predilection sites were as following: ileocecus (11/43, 25.58%), nasopharynx (10/43, 23.26%), faciomaxillary (9/43, 20.93%), superficial lymphadenopathy (8/43, 18.60%), other sites such as mediastinum and bone marrow (5/43, 11.63%). (5) With a median follow up of 24 months (0.7-105 months), the 2-year overall survival (OS) rate and event-free survival (EFS) rate were 79.8% ± 6.5%% and 71.0% ± 7.2%, respectively. The 2-year OS and EFS rates in patients treated with B-NHL-2010 protocol were 79.1% ± 8.4% and 74.1% ± 8.4%, while those in patients treated with LMB-89 protocol were 87.5% ± 8.3% and 66.7% ± 12.4%, respectively, but there was no significant difference between them (P > 0.05). The 2-year EFS rate in patients with LDH > 2N and bone marrow infiltration were significantly lower than that of other groups (P < 0.05). (6) 8 patients (18.6%) relapsed. The median relapsed time was 6 months (2-9 months). 1 patient suffered progressive disease. Male, systemic symptom, elevated LDH, bone marrow and CNS infiltration and advanced stage (stage III and stage IV) were associated with relapse /progressive disease. Logistic regression analysis showed that LDH > 2N was an independent unfavorable prognostic factors (OR = 31.129, P = 0.02).. Outcome of B-NHL/B-ALL is greatly improved by current intensive and short-time chemotherapy regimen. The 2-year event-free survival (EFS) rate is 71.0% ± 7.2%. There is no significant difference in EFS rate between patients treated with B-NHL-2010 protocol and LMB89 protocol. The long-term survival rate in patient with advanced disease need to be further improved.

Topics: Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Child; Cyclophosphamide; Cytarabine; Disease-Free Survival; Doxorubicin; Etoposide; Female; Humans; Hydrocortisone; Leucovorin; Logistic Models; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Multivariate Analysis; Neoplasm Staging; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Prognosis; Retrospective Studies; Survival Rate; Vincristine

Tumor lysis syndrome (TLS) is a potentially fatal metabolic complication of chemotherapy for Burkitt lymphoma. It has not been established whether chemotherapy should be delayed in patients with spontaneous TLS, and several studies have shown poor prognoses in this group. This retrospective study evaluated the efficacy and safety of continuous venovenous hemofiltration (CVVH) with prephase chemotherapy using the modified LMB-89 regimen in patients with Burkitt lymphoma and leukemia (BL/L) at a high risk of developing TLS from February 1998 to February 2007. The chemotherapy regimen was followed by the modified LMB-89 protocol. CVVH was applied to all patients before prephase chemotherapy or within 2 h of chemotherapy. The median follow-up was 19.7 months (range 1-97.8). Eight patients had Burkitt lymphoma and three had Burkitt leukemia; their median age was 48 years. The international prognostic indices were >3 for all patients. Seven patients had spontaneous TLS and four patients were at a high risk of TLS. CVVH was continued for 109 h (range 70.5-157.5). No patient had fatal metabolic complications related to TLS. Renal function had recovered fully before induction chemotherapy in all but one patient. The 1-year event-free survival and overall survival rates were both 82%. In conclusion, chemotherapy combined with CVVH might be effective and safe in patients with advanced Burkitt lymphoma and leukemia at a high risk of developing TLS.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Cyclophosphamide; Cytarabine; Doxorubicin; Etoposide; Female; Follow-Up Studies; Hemofiltration; Humans; Hydrocortisone; Hyperuricemia; Kidney Function Tests; Leucovorin; Male; Methotrexate; Middle Aged; Prednisone; Prognosis; Retrospective Studies; Risk; Survival Analysis; Tumor Lysis Syndrome; Vincristine

During the two last decades, the prognosis of children with Burkitt lymphoma has improved dramatically. Treating patients with Bukitt lymphoma in countries with limited resources is a challenge. We report our results in a serie of 95 children with Burkitt lymphoma treated between September 1990 and December 2000 according to SFOP LMB89 protocol. The median age was 45 months (range 8 months, 18 years). Seventy three percent of patients had abdominal tumor and 10% had maxillary tumor. According to Murphy classification, one patient had stage I, 17 patients stage II, 60 patients stage III and 17 patients stage IV. When considering the LMB prognosis groups, 1 patient was in group A, 83 were in group B and 11 were in group C. 73 patients were evaluables for treatment results. Complete remission was achieved in 50 patients, of whom 6 relapsed. 18 patients died from early treatment toxicity. The 5 years relapse free survival rate was 56%. It was at 100%, 84%, 52% and 38% for stage I, II, III and IV respectively. These results are below what is expected with this protocol. Improvement of supportive-care is the main condition to reach western results.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Doxorubicin; Etoposide; Female; Humans; Hydrocortisone; Infant; Leucovorin; Male; Methotrexate; Prednisone; Recurrence; Remission Induction; Survival Analysis; Vincristine

To compare outcomes of patients with HIV-Burkitt's lymphoma (HIV-BL) and HIV-diffuse large-cell lymphoma (HIV-DLCL) after treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or M-BACOD (methotrexate, bleomycin, cyclophosphamide, etoposide) in pre-highly active antiretroviral therapy (HAART) versus HAART eras.. Three hundred sixty-three patients with AIDS-related lymphoma diagnosed from 1982 to 2003 were reviewed retrospectively, including 262 in the pre-HAART (HIV-BL, 117; HIV-DLCL, 145) and 101 in the HAART era (HIV-BL, 18; HIV-DLCL, 83). Pre-HAART included those who did not receive HAART, and HAART era included those diagnosed after January 1997 who received HAART.. There were no significant differences between groups in terms of age, sex, history of injection drug use, prior AIDS, lactate dehydrogenase level, and disease stage at diagnosis. Compared with HIV-BL, HIV-DLCL was associated with significantly lower CD4 counts in the pre-HAART but not the HAART era. Although the overall median survival was similar for both groups in the pre-HAART era (HIV-BL, 6.4 months v HIV-DLCL, 8.3 months; P = .43), survival was significantly worse in patients with HIV-BL in the HAART era (HIV-BL, 5.7 months v HIV-DLCL, 43.2 months; P = .0003). Failure to attain complete remission and CD4 count less than 100 cells/mm(3) independently predicted for poor survival in the pre-HAART era. In comparison, histology of HIV-BL and no attainment of complete remission were independent poor prognostic factors in the HAART era.. Survival of patients with HIV-DLCL has improved in the HAART era, along with CD4 count, whereas survival of similarly treated patients with HIV-BL remained poor. The current practice of using the same regimen for both groups of patients should be re-evaluated.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; Bleomycin; Burkitt Lymphoma; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Humans; Leucovorin; Lymphoma, AIDS-Related; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Prednisone; Retrospective Studies; Survival Rate; Treatment Outcome; Vincristine

A very short, intensive paediatric chemotherapy programme was tested in a consecutive monoinstitutional group of 22 adult Burkitt's lymphoma (BL) patients. After a 5-week induction phase of weekly infusions consisting of vincristine, cyclophosphamide, doxorubicin, high-dose (HD) methotrexate (MTX) plus leukovorin rescue, and intrathecal MTX or cytarabine (ARA-C), a consolidation phase including HD ARA-C plus cisplatin was given. Responding patients achieving less than complete response (CR) after completion of the initial induction phase, were promptly shifted to a high-dose, stem cell supported sequential chemotherapy schema (R-HDS).. median age, 35.5 (range 18-76) years; Ann Arbor stage I-II/III-IV, 11/11; bulky disease, 15 patients; LDH > or = 460 U/l, 11 patients. The median duration of the chemotherapy programme was 62 d (range, 43-94 d). Seventeen patients achieved a CR (77%), one patient died of progressive disease and four partial responders following induction were converted to CR following R-HDS. Of 17 patients in CR, one died of infectious toxicity while in CR, and one relapsed at 30 months and died of progressive disease. After a median follow-up of 28.7 months (range, 6-158 months), 16 patients (73%) were in continued CR. Overall survival and progression-free survival were 77% [95% confidence interval (CI), 52-99%] and 68% (95% CI, 43-99%) respectively. Confirmation of these excellent efficacy and feasibility results by larger, multicentre and prospective studies is warranted.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Cyclophosphamide; Cytarabine; Disease Progression; Doxorubicin; Drug Administration Schedule; Female; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Retrospective Studies; Salvage Therapy; Survival Rate; Treatment Outcome; Vincristine

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

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

We describe the case of a 35-year old male who developed acute renal failure following high dose methotrexate therapy for Burkitt's non Hodgkin lymphoma. Serum methotrexate levels reached 37 micromol/l, and remained higher than 1 micromol/l for more than a week. Folinic acid rescue was intensified to 200-400 mg intravenously every 4 hours. As methotrexate binds markedly to proteins, plasma exchange was initially chosen, 4 sessions being performed from day 2 to day 4. The methotrexate pharmacokinetic profile was not significantly modified during plasma exchange, and serum drug level was 3 micromol/l. Continuous veno-venous hemodiafiltration was therefore performed from day 5 to day 10. This procedure also seemed ineffective, with evidence of low ultrafiltrate clearance. No extrarenal toxicity was observed in our patient. Thus, conventional extrarenal procedures appear to have a limited role in the setting of overexposure to methotrexate. The use of very high doses of folinic acid in our case probably played a major role in the eventual favorable outcome.

Topics: Acute Kidney Injury; Adult; Antidotes; Burkitt Lymphoma; Dose-Response Relationship, Drug; Humans; Leucovorin; Male; Methotrexate

Urinary N-acetyl-beta-D-glucosaminidase (NAG-ase) activity is a very sensitive parameter of kidney proximal tubular damage. Using urinary NAG-ase activity/urinary creatinine as the NAG index, the serum methotrexate (MTX) level and urinary pH were investigated simultaneously. These parameters were measured in 17 leukaemic children. During MTX treatment, NAG indices were normal in 5 children and only slightly elevated occasionally in 9 patients. Among them, transiently high serum MTX levels (Patient A) or low urinary pH (Patient B) were accompanied by high NAG indices. MTX toxicity has been diagnosed in 3 cases, when permanently high NAG indices were in accordance with other clinical signs.

Topics: Acetylglucosaminidase; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Burkitt Lymphoma; Child; Creatinine; Diuresis; Humans; Hydrogen-Ion Concentration; Kidney Diseases; Kidney Tubules, Proximal; Leucovorin; Leukemia; Lymphoma, Non-Hodgkin; Methotrexate; Neoplasm Proteins; Precursor Cell Lymphoblastic Leukemia-Lymphoma

An intensive 6-month schedule of drugs was devised with both systemic and central nervous system activity, known by the acronym 'MACHO', to treat 24 newly and consecutively diagnosed children, 13 with stage IV B-cell non-Hodgkin's lymphoma (B-NHL) and 11 with B-cell acute lymphoblastic leukaemia (B-ALL). There were three deaths from complications of chemotherapy (two infective, one biochemical). Five children with central nervous system disease at diagnosis (CNS+) received planned additional megatherapy/bone marrow transplants. Event-free survival (EFS) at 1 year for the 11 cases of B-ALL is 64% (95% confidence intervals [CI] 31-89%) and of 13 stage IV B-NHL cases is 50% (95% CI 19-75%). Patients with bulky abdominal disease had a 32% EFS at 1 year (CI 13-68%) compared with 76% (CI 39-94%) for those without bulky abdominal disease. Overall EFS for eight CNS+ patients is 73% at 1 year (95% CI 34-97%) compared with 48% (95% 24-74%) for those without CNS disease (CNS-). However, only two of the CNS+ cases had bulky abdominal disease (patients 10 and 12) and the difference is not significant (P less than 0.5). A score of 1 was given for each of the following potential prognostic features: bulky abdominal disease, pleural effusion and severe renal dysfunction within 48 h of presentation. Patients who scored 0 or 1 fared significantly better than those who scored 2 or 3 (EFS at 1 year 78% [CI 49-95%] versus 24% [6-65%], P less than 0.04). Two patients with a score of 2 survived past 6 months and another is currently well, but has not regenerated his marrow following autologous transplantation. This protocol is relatively effective for patients who have B-ALL, but those patients who have bulky abdominal disease, often associated with severe renal dysfunction, and those with CNS disease, do not fare so well and require new approaches to therapy.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Doxorubicin; Female; Humans; Leucovorin; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Male; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Vincristine

Two patients who underwent autologous bone marrow transplantation for recurrent non-Hodgkin's lymphoma relapsed at 46 and 28 days after the transplant. Both patients had an HLA-identical sibling and were treated with high-dose chemotherapy and allogeneic marrow transplantation. One patient is now 24 months after the allogeneic transplant without evidence of disease. The second patient died on day 7 with interstitial pneumonia. We conclude that high-dose therapy and allogeneic bone marrow transplantation after failure of autologous transplantation for non-Hodgkin's lymphoma is feasible and should be considered in young patients with HLA-identical siblings.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Transplantation; Burkitt Lymphoma; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Humans; Leucovorin; Lymphoma, Non-Hodgkin; Male; Methotrexate; Prednisone; Reoperation; Transplantation, Autologous; Transplantation, Homologous; Vincristine

The cytotoxicity of 7-hydroxymethotrexate (7-OH-MTX), the primary plasma metabolite of methotrexate (MTX) in humans, was assessed by inhibition of colony formation in agar, using human bone marrow granulocyte-macrophage stem cells (CFU) from healthy volunteers and RAJI cells, a human Burkitt's lymphoma cell line. After a 2 hr exposure of cells to 7-OH-MTX, the concentrations necessary to produce a 50% inhibition of colony formation were 180 microM and 10 microM for bone marrow cells and for RAJI cells respectively. A continuous incubation with 20 microM folinic acid (CF) protected the RAJI cells from 7-OH-MTX cytotoxicity at concentrations below 5 microM but was not able to completely reverse 7-OH-MTX effects at higher doses. Continuous incubation of 7-OH-MTX-preloaded cells (2 hr, ID90) with the end products of folate-dependent reactions, adenosine (100 microM) and thymidine (10 microM), completely rescued RAJI cells from the 7-OH-MTX cytotoxic effects. Moreover, while thymidine alone had no effect on the 7-OH-MTX response curve, both adenosine alone or CF-adenosine combination produced 75% and 90% protection respectively. CF and adenosine concentrations necessary to achieve 90% protection were 20 and 100 microM respectively. This study demonstrates that 7-OH-MTX can exhibit a cytotoxic selectivity for this human Burkitt's lymphoma cell line as compared to human bone marrow stem cells and the cytotoxicity of 7-OH-MTX cannot be reversed by CF alone. These data suggest that 7-OH-MTX and/or its polyglutamylated derivatives may play an important role on different enzyme(s) involved in the interconversion of tetrahydrofolate cofactors necessary for the de novo purine biosynthesis.

Topics: Burkitt Lymphoma; Cell Line; Colony-Forming Units Assay; Folic Acid Antagonists; Granulocytes; Hematopoietic Stem Cells; Humans; Leucovorin; Methotrexate

Malignant lymphomas, Burkitt's type, and B-ALL are rarely encountered in adult patients. Rapid initial responses are usually followed by early relapse and death. In a pilot study four adult patients, two presenting with B-ALL, were successfully treated with an aggressive protocol developed by the BFM study group for childhood lymphomas of B-type. Rapid clearance of tumor masses was achieved in all patients; no relapse occurred during an observation period ranging from 19-33 months of complete remission.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; B-Lymphocytes; Burkitt Lymphoma; Cyclophosphamide; Cytarabine; Doxorubicin; Female; Humans; Infusions, Parenteral; Injections, Spinal; Leucovorin; Leukemia, Lymphoid; Male; Methotrexate; Middle Aged; Prednisolone; Teniposide

Topics: Adult; Burkitt Lymphoma; Cerebral Ventricles; Humans; Injections, Spinal; Leucovorin; Male; Medication Errors; Methotrexate; Perfusion; Spinal Puncture

In summer 1978, Burkitt lymphoma was diagnosed in a 23 year old Swiss male. A brief report on this patient appears justified for the following reasons: (1) Burkitt lymphoma is very rarely diagnosed in Switzerland. (2) The tumor cells of this patient could be established as a cell line. They have now been subpassaged in vitro for over 9 months. (3) In contrast to the majority of non-African Burkitt lymphomas, these tumor cells produce small amounts of Epstein-Barr virus.

Topics: Adult; Brain Neoplasms; Burkitt Lymphoma; Cell Line; Cerebrospinal Fluid; Herpesvirus 4, Human; Humans; Leucovorin; Male; Methotrexate; Switzerland