Long-term outcome after allogeneic hematopoietic stem cell transplantation for advanced stage acute myeloblastic leukemia: a retrospective study of 379 patients reported to the Société Française de Greffe de Moelle (SFGM)

To assess the place of allogeneic hematopoietic stem cell transplantation (HSCT) in the advanced stage of acute myeloid leukemia (AML), we retrospectively analyzed 379 consecutive patients who underwent allogeneic HSCT for advanced AML. The median follow-up of the entire cohort was 7.5 years. Sixty-nine patients (18%) were transplanted with primary resistant disease. Three hundred and ten (82%) were relapsed patients, 94 (30%) of whom were in untreated relapse, 67 (22%) in refractory relapse and 149 (48%) in 2nd or 3rd complete remission at time of transplantation. The 5-year probabilities of overall survival (OS), disease-free survival (DFS), and transplant-related mortality (TRM) were 22 +/- 4%, 20 +/- 4%, 45 +/- 6%, respectively. In multivariate analysis, we demonstrated the favorable impact on OS, DFS and TRM of two factors over which we have no control (age <15 years, complete remission achievement) and three factors over which we have some control (female donor, acute and chronic graft-versus-host disease). The results of this study suggest that the graft-versus-leukemia effect is important in advanced AML and that new HSCT modalities are needed for some patients with this indication.     

Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study

A phase III prospective randomized multicenter study was performed to determine whether quinine could improve the response rate of poor-risk acute leukemias (ALs) to standard chemotherapy including a multidrug resistance (MDR)-related cytotoxic agent. The rationale of the study was based on the negative prognostic value of MDR phenotype in ALs and the ability of quinine to reverse this phenotype both in vitro and ex vivo. Three hundred fifteen patients (median age, 49 years; range, 16 to 65) with relapsed (n = 108) or refractory (n = 32) acute myeloblastic leukemia (AML), relapsed (n = 27) or refractory (n = 9) acute lymphoblastic leukemia (ALL), secondary AL (n = 22) or blastic transformation of myelodysplastic syndrome ([MDS] n = 74) or myeloproliferative syndrome ([MPS] n = 43) were randomly assigned to receive mitoxantrone ([MXN] 12 mg/m2/d, days 2 to 5) and cytarabine ([Ara-C] 1 g/m2/12 h, days 1 to 5) alone or in combination with quinine (30 mg/kg/d, days 1 to 5; continuous intravenous infusion beginning 24 hours before MXN infusion). Side effects of quinine were observed in 56 of 161 quinine-treated patients and disappeared in all but four cases after one or two 20% dose decreases. Sera from quinine-treated patients showed increased MXN uptake in an MDR-positive cell line compared with matched sera obtained before quinine infusion. Quinine induced a significant increase in the incidence of nausea, vomiting, mucositis, and cardiac toxicity. A complete response (CR) was observed in 85 of 161 patients (52.8%) from the quinine-treated group versus 70 of 154 patients (45.5%) in the control group (P = .19). The most important differences between quinine and control group CR rates were observed in patients with refractory AMLs and blastic transformation of MDS and MPS. The CR rate was higher in P-glycoprotein-positive cases, although the difference was not significant. Failure of the regimen due to blastic persistence or blast number increase was higher in the control group (61 of 154 patients) than in the quinine group (45 of 161, P = .04). Early death was observed in eight cases (four in each arm) and death in aplasia in 27 cases (20 in quinine group v seven in control group, P = .01). The significant increase of toxicity in the quinine arm could have masked the clinical benefit of MDR reversion in poor- risk ALs.     

Comparison of chemotherapy to radiotherapy as consolidation of complete or good partial response after six cycles of chemotherapy for patients with advanced Hodgkin's disease: results of the groupe d'études des lymphomes de l'Adulte H89 trial

The treatment of advanced Hodgkin's disease (HD) with chemotherapy (CTx) alone or combined modality treatments has been controversial. In 1989, we designed a randomized study to compare 2 cycles of CTx to (sub)total nodal irradiation (RTx) as consolidation treatments for patients with stage IIIB/IV HD in complete remission (CR) or good partial response after 6 cycles of CTx. A total of 559 patients were randomized to receive 6 cycles of MOPP/ABV (mechlorethamine, vincristine, procarbazine, prednisone/Adriamycin [doxorubicin], bleomycin, vinblastine) hybrid (n = 266) or ABVPP (n = 267). After induction treatment, 418 patients could be evaluated for the consolidation phase. With a median follow-up of 48 months, the 5-year disease-free survival estimates were 80% for 8 cycles of MOPP/ABV, 82% for 6 cycles of MOPP/ABV plus RTx, 68% for 8 cycles of ABVPP, and 75% for 6 cycles of ABVPP plus RTx (P =.01). The 5-year disease-free survival estimates did not differ between CTx and RTx, 74% and 79%, respectively (P =.07). After MOPP/ABV, the 5-year overall survival estimates did not differ between CTx and RTx, 85% and 88%, respectively (P =.2). After ABVPP, the 5-year survival estimates were 94% for CTx and 78% for RTx (P =.002). These results showed that RTx was not superior to CTx consolidation after doxorubicin-induced CR for patients with advanced HD. Because of the uncertainty of obtaining a prolonged second remission for patients relapsing after CTx and RTx and the possible long-term effects of RTx, we prefer 8 cycles of CTx as standard treatment when a CR has been achieved after 6 cycles.     

Non-Hodgkin's lymphomas with t(11;14)(q13;q32): a subset of mantle zone/intermediate lymphocytic lymphoma?

We here describe 13 patients with non-Hodgkin's lymphoma (NHL) and a translocation t(11:14)(q13:q32). They were part of a series of 163 patients with NHL and an abnormal karyotype, serially referred to our institution between January 1984 and 1990. Patients with t(11:14) seem to present several common and interesting features. Males are more frequently affected than females, and old people more than young. They present at diagnosis with advanced disease and usually show involvement of epithelium and bone marrow. With respect to histologic diagnoses, these patients are usually considered to be of low-grade malignancies. However, most of them do very poorly, have short complete remission and frequent relapses whatever the treatment. As a whole, the median survival rate is rather low. The cytologic, histologic as well as the immunologic patterns tend to be uniform: tumours are composed of small cells and display features of mantle zone/intermediate lymphocytic lymphoma. They express high IgM and low IgD levels and more commonly bear Ig lambda light chains. They also express all pan-B antigens (except CD23) as well as the CD5 antigen, but usually lack the CD10. According to these characteristics, these tumours could be placed in between lymphocytic lymphomas (which usually express CD23) and follicular lymphomas (which commonly lack IgD and CD5 and bear CD10 as well as a t(14:18).     

A retrospective series of gut aspergillosis in haematology patients

Gut invasive aspergillosis is an extremely rare infection in immunocompromised patients. The goal of this retrospective multicentre study is to report on cases of gut aspergillosis in haematology patients, including clinical presentation, risk factors, and outcome. Twenty-one patients from nine centres were identified. Eight had isolated gut aspergillosis, with no evidence of other infected sites, and 13 had disseminated aspergillosis. Thirteen patients had acute leukaemia. Nine were allogeneic stem cell transplant recipients. Clinical symptoms and imaging were poorly specific. The galactomannan antigenaemia test result was positive in 16/25 (64%) patients, including in four of the eight cases of isolated gut aspergillosis. Five of 21 patients had a dietary regimen rich in spices, suggesting that, in these cases, food could have been the source of gut colonization, and then of a primary gut Aspergillus lesion. The diagnosis was made postmortem in six patients. The mortality rate in the remaining patients at 12 weeks was 7/15 (47%). Gut aspergillosis is probably misdiagnosed and underestimated in haematology patients, owing to the poor specificity of symptoms and imaging. Patients with a persistently positive galactomannan antigenaemia finding that is unexplained by respiratory lesions should be suspected of having gut aspergillosis in the presence of abdominal symptoms, and be quickly investigated. In the absence of severe abdominal complications leading to surgery and resection of the lesions, the optimal treatment is not yet defined.     

Heterogeneity of t(4;14) in multiple myeloma. Long-term follow-up of 100 cases treated with tandem transplantation in IFM99 trials.

One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10(-7)). We identified a subgroup of patients presenting at diagnosis with both low beta(2)-microglobulin <4 mg/l and high hemoglobin (Hb) >/=10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high beta(2)-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.