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While commonly accepted in poor-risk acute lymphoblastic leukemia (ALL), the role of allogeneic hematopoietic stem cell transplantation (allo-SCT) is still disputed in adult patients with standard-risk ALL. We evaluated outcome of patients with ALL in first complete remission (CR1), according to a sibling donor versus no-donor comparison. Eligible patients (433) were entered in 2 consecutive, prospective studies, of whom 288 (67%) were younger than 55 years, in CR1, and eligible to receive consolidation by either an autologous SCT or an allo-SCT. Allo-SCT was performed in 91 of 96 patients with a compatible sibling donor. Cumulative incidences of relapse at 5 years were, respectively, 24 and 55% for patients with a donor versus those without a donor (hazard ratio [HR], 0.37; 0.23-0.60; P < .001). Nonrelapse mortality estimated 16% (± 4) at 5 years after allo-SCT. As a result, disease-free survival (DFS) at 5 years was significantly better in the donor group: 60 versus 42% in the no-donor group (HR: 0.60; 0.41-0.89; P= .01). After risk-group analysis, improved outcome was

We conducted a cohort-study among 518 female 5-year Hodgkin lymphoma (HL) survivors, aged 14 to 40 years (median: 25 years) at treatment (1965-1995). Multivariable Cox regression was used to quantify treatment effects on risk of premature menopause, defined as cessation of menses before age 40 years. After a median follow up of 9.4 years, 97 women had reached menopause before age 40 years. Chemotherapy was associated with a 12.3-fold increased risk of premature menopause compared with radiotherapy alone. Treatment with MOPP (mechlorethamine, vincristine, procarbazine, prednisone)/ ABV (doxorubicine, bleomycine, vinblastine) significantly increased the risk of premature menopause (hazard ratio [HR]: 2.9), although to a lesser extent than MOPP treatment (HR: 5.7). Alkylating agents, especially procarbazine (HR: 8.1) and cyclophosphamide (HR: 3.5), showed the strongest associations. Ten years after treatment, the actuarial risk of premature menopause was 64% after high cumulative doses (> 8.4 g/m2) and 15% after low doses (≤ 4.2 g/m2) of procarbazine. The cumulative risk of menopause at age 40 years did not differ much according to age, but time to premature menopause was much longer in women treated at early ages. As long as alkylating agents will be used for curing HL, premature menopause will remain a frequent adverse treatment effect, with various clinical implications.

We evaluated the role of rituximab during remission induction chemotherapy in relapsed aggressive CD20+non-Hodgkin lymphoma. Of 239 patients, 225 were evaluable for analysis. Randomized to DHAP (cisplatin-cytarabine- dexamethasone)-VIM (etoposide-ifosfamide-methotrexate)-DHAP (cisplatin- cytarabine-dexamethasone) chemotherapy with rituximab (R; R-DHAP arm) were 119 patients (113 evaluable) and to chemotherapy without rituximab (DHAP arm) 120 patients (112 evaluable). Patients in complete remission (CR) and partial remission (PR) after 2 chemotherapy courses were eligible for autologous stem-cell transplantation. After the second chemotherapy cycle, 75% of the patients in the R-DHAP arm had responsive disease (CR or PR) versus 54% in the DHAP arm (P = .01). With a median follow-up of 24 months, there was a significant difference in failure-free survival (FFS24; 50% vs 24% vs, P < .001), and progression free survival (PFS24; 52% vs 31% P < .002) in favor of the R-DHAP arm. Cox-regression analysis demonstrated a significant effect of rituximab treatment on FFS24(HR 0.41, 95% confidence interval [CI] 0.29-0.57 versus 0.51, 95% CI 0.37-0.70) and overall-survival (OS24: HR 0.60 [0.41-0.89] vs 0.76 [0.52-1.10]) when adjusted for time since upfront treatment, age, World Health Organization performance status, and secondary age-adjusted international prognostic index. These results demonstrate improved FFS and PFS for relapsed aggressive B-cell NHLif rituximab is added to the re-induction chemotherapy regimen.

BACKGROUND: Treatment of early-stage Hodgkin's disease is usually tailored in line with prognostic factors that allow for reductions in the amount of chemotherapy and extent of radiotherapy required for a possible cure. METHODS: From 1993 to 1999, we identified 1538 patients (age, 15 to 70 years) who had untreated stage I or II supradiaphragmatic Hodgkin's disease with favorable prognostic features (the H8-F trial) or unfavorable features (the H8-U trial). In the H8-F trial, we compared three cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) combined with doxorubicin, bleomycin, and vinblastine (ABV) plus involved-field radiotherapy with subtotal nodal radiotherapy alone (reference group). In the H8-U trial, we compared three regimens: six cycles of MOPP-ABV plus involved-field radiotherapy (reference group), four cycles of MOPP-ABV plus involved-field radiotherapy, and four cycles of MOPP-ABV plus subtotal nodal radiotherapy. RESULTS: The median follow-up was 92 months. In the H8-F trial, the estimated 5-year eventfree survival rate was significantly higher after three cycles of MOPP-ABV plus involved-field radiotherapy than after subtotal nodal radiotherapy alone (98% vs. 74%, P<0.001). The 10-year overall survival estimates were 97% and 92%, respectively (P = 0.001). In the H8-U trial, the estimated 5-year event-free survival rates were similar in the three treatment groups: 84% after six cycles of MOPP-ABV plus involved-field radiotherapy, 88% after four cycles of MOPP-ABV plus involved-field radiotherapy, and 87% after four cycles of MOPP-ABV plus subtotal nodal radiotherapy. The 10-year overall survival estimates were 88%, 85%, and 84%, respectively. CONCLUSIONS: Chemotherapy plus involved-field radiotherapy should be the standard treatment for Hodgkin's disease with favorable prognostic features. In patients with unfavorable features, four courses of chemotherapy plus involved-field radiotherapy should be the standard treatment. (Cli

We assessed cardiovascular disease (CVD) incidence in 1474 survivors of Hodgkin lymphoma (HL) younger than 41 years at treatment (1965-1995). Multivariable Cox regression and competing risk analyses were used to quantify treatment effects on CVD risk. After a median follow-up of 18.7 years, risks of myocardial infarction (MI) and congestive heart failure (CHF) were strongly increased compared with the general population (standardized incidence ratios [SIRs] = 3.6 and 4.9, respectively), resulting in 35.7 excess cases of MI and 25.6 excess cases of CHF per 10 000 patients/year. SIRs of all CVDs combined remained increased for at least 25 years and were more strongly elevated in younger patients. Mediastinal radiotherapy significantly increased the risks of MI, angina pectoris, CHF, and valvular disorders (2- to 7-fold). Anthracyclines significantly added to the elevated risks of CHF and valvular disorders from mediastinal RT (hazard ratios [HRs] were 2.81 and 2.10, respectively). The 25-year cumulative incidence of CHF after mediastinal radiotherapy and anthracyclines in competing risk analyses was 7.9%. In conclusion, risks of several CVDs are 3- to 5-fold increased in survivors of HL compared with the general population, even after prolonged follow-up, leading to increasing absolute excess risks over time. Anthracyclines further increase the elevated risks of CHF and valvular disorders from mediastinal radiotherapy.

The feasibility and efficacy of up-front high-dose sequential chemotherapy followed by autologous stem cell transplantation (ASCT) in previously untreated adults (median age 33 years; range 15-64) with Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL) or lymphoblastic lymphoma (LyLy), both without central nervous system or extensive bone marrow involvement was investigated in a multicenter phase II study. Treatment consisted of two sequential high-dose chemotherapy induction courses incorporating prednisone, cyclophosphamide, doxorubicin, etoposide and mitoxantrone, without high-dose methotrexate or high-dose cytarabine. Patients with at least PR went on with BEAM and ASCT. Protocol treatment was completed by 23/27 (85%) BL/BLL and 13/15 (87%) LyLy patients. Median treatment duration until BEAM was 70 (range: 50-116) days. No toxic deaths occurred. Response to treatment was complete response (CR) 81% and partial response (PR) 11% for BL/BLL, CR 73% and PR 20% for LyLy. At a median follow-up of 61 months of patients still alive, six BL/BLL and eight LyLy patients have died. The actuarial 5-year overall and event-free survival estimates are 81 and 73% for BL/BLL vs 46 and 40% for LyLy patients. In conclusion, this short up-front high-dose sequential chemotherapy regimen, followed by ASCT is highly effective in adults with BL/BLL with limited bone marrow involvement, but less so in patients with LyLy.

Thrombocytopenia is a well-known side effect following intramuscular gold therapy in patients with rheumatoid arthritis. Thrombocytopenia may occur at any time and it can be irreversible and sometimes fatal despite cytotoxic or immunosuppressive therapy. We describe two patients who presented with haemorrhagic diathesis on the day after the administration of aurothioglucose. The thrombocytopenia in these patients was caused by aurothioglucose-induced antibody-mediated platelet destruction. Both patients made an uneventful recovery and the platelet count returned to normal within several

This study involved 12 patients with multiple myeloma (MM), in whom malignant plasma cells did not contain immunoglobulin heavy chain (IgH) protein chains. Southern blot analysis revealed monoallelic J(H) gene rearrangements in 10 patients, biallelic rearrangement in 1 patient, and biallelic deletion of the J(H) and C(micro) regions in 1 patient. Heteroduplex polymerase chain reaction analysis enabled the identification and sequencing of 9 clonal J(H) gene rearrangements. Only 4 of the joinings were complete V(H)-(D)-J(H) rearrangements, including 3 in-frame rearrangements with evidence of somatic hypermutation. Five rearrangements concerned incomplete D(H)-J(H) joinings, mainly associated with deletion of the other

In the period from August 1991 to August 1994, the Dutch Slide Review Committee of Adult Leukemias classified 14 leukemias as AML-M0. We reviewed the clinical characteristics and response to therapy of these patients. Eight patients were male. Patients' age ranged from 7 to 77 years (medium age 62 years). There was a striking homogeneity in morphological appearance of the blasts, being small to medium-sized round cells with often an eccentric nucleus with fine chromatin, several distinct nucleoli, and a high nucleo-cytoplasmic ratio. In addition to myeloid-associated markers such as CD13 and CD33, the blasts of all patients were positive for CD34 and HLA-DR, pointing to their immature differentiation stage. TdT was present in the blasts of 71%, CD7 was positive in the blasts of 42% of the patients. No consistent cytogenetic abnormalities were found. With respect to the treatment outcome, four patients achieved a complete remission after remission-induction treatment. The median survival was 4.5 months. Our present study shows AML-M0 to be an immature leukemia, uniform in morphology and immunological phenotype, with no consistent cytogenetic phenotype and with a poor clinical outcome.