Prospective randomized study comparing MEMID with a chop-like regimen in elderly patients with aggressive non-Hodgkin's lymphoma.

OBJECTIVE: This multicenter phase III study compared the MEMID regimen (mitoxantrone, VP16, methylglyoxal, ifosfamide and dexamethasone) with CEOP, a CHOP-like regimen (cyclophosphamide, epirubicin, vincristine and prednisone), in elderly patients (> or =65 years) with aggressive non-Hodgkin's lymphoma (NHL). METHODS: One hundred and forty-nine patients were eligible, 72 in the MEMID arm and 77 in the CEOP arm. The primary endpoint was to compare overall survival (OS) between groups, and secondary endpoints were event-free survival (EFS), response rate and toxicity. RESULTS: Neutropenia (p < 10(-5)), anemia (p < 10(-5)) and thrombocytopenia (p = 0.0006) were significantly more frequent in patients who received MEMID. We observed an objective response rate of 55.5% in the MEMID arm and 64.9% in the CEOP arm (p = 0.24). The median OS and EFS were 15.4 and 8.5 months in the MEMID arm, and 20.3 and 10.5 months in the CEOP arm (p = 0.59 and 0.47), respectively. The median EFS was 15.4 months in the MEMID arm and 20.3 months in the CEOP arm (p = 0.59). CONCLUSION: The increased toxicity without survival benefit confirms the superiority of CHOP and CHOP-like regimens for elderly patient with aggressive NHL.

Graft-versus-leukemia effect in allogeneic marrow transplant recipients with acute leukemia is maintained using cyclosporin A combined with methotrexate as prophylaxis. Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

A total of 1634 recipients of HLA-identical sibling bone marrow with acute leukemia were treated with the combination of cyclosporin A (CsA) and methotrexate as prophylaxis against graft-versus-host disease (GVHD). The probability of relapse decreased with an increasing grade of acute GVHD, especially in patients grafted in first remission (CR-1): P < 0.01 and P < 0.001 for acute lymphoblastic leukemia and acute myeloid leukemia, respectively. Among patients surviving at least 3 months without a relapse, chronic GVHD was associated with a decreased incidence of relapse in CR-1 (P < 0.0001 for both diagnoses), and a better LFS. Among patients in CR-1, the probability of relapse was the same in those with limited or with extensive chronic GVHD. However, in patients with intermediate stage of the disease (> or = 2nd remission or 1st relapse) with previous acute GVHD, those with extensive chronic GVHD had a reduced probability of relapse (P = 0.05). The graft-versus-leukemia effect of acute and especially chronic GVHD was confirmed by multivariate analyses. Overall, the highest LFS was seen in patients with chronic GVHD and no or grades I-II acute GVHD. The lowest LFS was seen in patients having acute GVHD grades III-IV without chronic GVHD.

A pilot study of autologous bone marrow transplantation followed by recombinant interleukin-2 in malignant lymphomas.

In this study, we investigated the impact of recombinant interleukin-2 (rIL-2) after high dose chemotherapy and autologous bone marrow transplantation (ABMT) in 25 patients with refractory or relapsed Hodgkin's disease (HD) (11 patients) and non Hodgkin's lymphoma (NHL) (14 patients). 48% of patients had resistant disease, 84% achieved complete remission after ABMT. rIL-2 was started at a median of 54 days post-transplant and consisted of a first cycle of 5 days followed by 4 cycles of 2 days every other week. Patients received a mean of 160 x 10(6) IU/m2 rIL-2 and hematological toxicity was moderate and transient. None of the 5 evaluable patients with measurable disease responded to rIL-2. After a 5 year median follow-up, the probability of survival and DFS is 72% (HD: 73% and NHL: 70%, p = NS) and 45% (HD: 36% and NHL: 48%, p = NS) respectively. These somewhat encouraging results warrant further evaluation of rIL-2 after ABMT in controlled studies, especially in NHL patients stratified for previous chemosensitivity.

HLA-target antigens and T-cell receptor diversity of activated T cells invading the skin during acute graft-versus-host disease.

To study the repertoire and specificity of T lymphocytes infiltrating skin lesions during graft-versus-host disease (GVHD), we performed an exhaustive molecular and functional analysis of 146 T-cell clones derived from the skin of three patients undergoing an acute GVHD after allogeneic bone marrow transplantation (BMT) from HLA-mismatched related donors. Analysis of T-cell receptor (TCR) rearrangement and TCR chain junctional sequences demonstrated the presence of 11 distinct clones among the 64 derived from patient UPN1, six among the 58 derived from patient UPN2, and seven among the 24 derived from patient UPN3. Three of the 11 T-cell clones from patient UPN1, and all clones from patients UPN2 and UPN3 reacted with mismatched HLA alleles between the bone-marrow donor and recipient. Moreover, both HLA class I (HLA-A2 and -B27) and class II (HLA DP101, DP401, DP1301, DQ8, and DR402) molecules were recognized during this early antihost response. Finally, both TCR alpha and beta chains turned out to be extremely diverse, even within populations of clones derived from the same patient and directed against the same HLA allele. Taken together, these results indicate that any HLA mismatch is potentially targeted during early GVHD, and that the T-cell response at the onset of GVHD is both oligoclonal and highly diversified.

[Acute monoblastic leukaemia. Clinical data and therapeutic results in 74 patients (author's transl)]. / Leucémie aiguë monoblastique. Données cliniques et thérapeutiques. 74 observations.

Seventy-four patients with acute pure monoblastic leukaemia treated between 1970 and 1978 were studied retrospectively. The disease was usually hyperleucocytic and tumoral in character. It occurred with equal frequency in subjects of both sexes and at all ages, with peaks at the two extremes of life. Rubidazone gave a high percentage (75%) of complete remissions, but the prognosis remained sombre, with a mean survival time of 200 days. The incidence of meningeal relapses was reduced by prophylactic measures at central nervous system level, but gingival and cutaneous relapses were frequent. The possibility of bettering the present modest therapeutic results by more intensive chemotherapy is discussed.

Acute monoblastic leukemia: a clinical and biologic study of 74 cases.

Seventy-four cases of pure acute monoblastic leukemia (AMol) have been retrospectively studied. All patients were treated at Hospital Saint-Louis between 1970 and 1978. Diagnosis was based on morphological and cytochemical features according to the FAB classification. This type of leukemia occurred at any age and in both sexes, with a high frequency of extramedullary involvements. Hyperleukocytosis was very frequent and was significantly correlated with increased blood and urine levels of lysozyme, with renal failure and hypokalemia, and with coagulation abnormalities. AMol still has a poor prognosis, despite a best remission rate (75%) obtained with rubidazone, since the duration of complete remission was short. Central nervous irradiation prolonged remission and prevented meningeal relapses, while 6 meningeal relapses occurred in the patients not irradiated. The high frequency of the extramedullary relapses, including gum and skin, emphasized the question of persistant blast cell sanctuaries after achievement of bone marrow remissions. A more intensive induction with several drugs active against monoblasts could be more efficient and prolong the duration of complete remissions.