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Primary mediastinal B-cell lymphoma (PMBL) is a clinicopathological entity among the world health organization classification of lymphoid neoplasms. PMBL often concerns young adults, and the disease remains a localized disease in the majority of cases. The outcome of patients with PMBL is variable and unlike diffuse large cell lymphomas, the international prognostic index seems to be less applicable to such disease. The combination of rituximab and chemotherapy is the gold standard treatment of patients with good prognosis features and allows high cure rates. However, high-dose chemotherapy supported by peripheral blood stem cell support is often warranted in poor-prognosis patients. The use of positrons emission tomography examination is more and more used in such situations to select the best therapeutic strategy., (Copyright (c) 2010. Published by Elsevier Masson SAS.)

The aim of this retrospective analysis was to assess the benefit of reduced-intensity conditioning allo SCT (RIC allo-SCT) in a cohort of 32 relapsed multiple myeloma (MM) patients. A total of 19 patients had an HLA-identical sibling donor ('donor' group), while 13 patients had no donor ('no-donor' group). There were no significant differences between these two groups as for prognosis risk factors. Eighteen patients from the 'donor' group could actually proceed to RIC allo-SCT. With a median follow-up of 36 (range, 21-60) months, six patients died from transplant-related toxicity (cumulative incidence, 33% (95% CI, 11-55%)). Only 4 patients from the 18 transplanted patients (22%; 95% CI, 7-48%) progressed after RIC allo-SCT, as compared to 12 (86%; 95% CI, 56-98%; P=0.0003) among the nontransplanted patients. In an 'intention-to-treat' analysis, the Kaplan-Meier estimate of PFS was significantly higher in the 'donor' group as compared to the 'no-donor' group (P=0.01; 46 versus 8% at 3 years). There was no difference in terms of overall survival. However, in multivariate analysis, actual performance of RIC allo-SCT was associated with better PFS (relative risk, 0.35; 95% CI, 0.15-0.82; P=0.01). These data suggest a potential benefit for RIC allo-SCT in the management of relapsed MM warranting further prospective investigations.

Introduction: Chronic lymphocytic leukemia (CLL) is the most common leukaemia in the Western world. Recent advancement in the aetiology, pathophysiology and the development of new therapeutics tools have significantly modified the current management of CLL., Current Knowledge and Key Points: The cellular origin of CLL is still unknown. The current main hypothesis will be first briefly described. This review will then focus on the newly defined prognostic factors and the development and use of new drugs for the treatment of CLL. To describe the modern and practical management of CLL, we will compare classical and new prognostic markers. Then, we will discuss the various therapeutic options including chemotherapy and immunotherapy (monoclonal antibodies, allogenic transplantation), and define their current respective indications., Future Prospects and Projects: These new diagnostic and prognostic markers will allow the characterization of new prognostic subgroups of patients. This will lead to a targeted and individualized therapeutic approach. We will present the first results of clinical trials and the on-going studies conducted in this disease.

Background: Adverse events (AEs) after hematopoietic progenitor cell (HPC) infusion are rare but might be life-threatening. These reactions have traditionally been associated with the amount of infused cryoprotectant, but persistence of such events after dimethyl sulfoxide (DMSO) depletion has questioned this assumption., Study Design and Methods: The incidence of AEs on a cohort of 460 patients (490 HPC infusions) undergoing autologous DMSO-reduced HPC transplantation was prospectively evaluated. HPCs were collected from adult patients with various hematologic or solid malignancies. After quality control (QC) on fresh apheresis products and subsequent cryopreservation, HPC grafts were thawed and washed at the cell therapy facility. QC was performed on each graft after washing, and clinical data were collected for each infusion., Results: AEs were reported in 66 cases (13.5%) and were graded according to the NCI-CTC scale from 1 to 4. Although none of the factors associated with patient characteristics or infusion procedure were different between the two groups (no AE vs. occurrence of AE), it was found that the absolute number of granulocytes measured before freezing was considerably higher in the AE group. Furthermore, within this group, there was a strong correlation between the amount of granulocytes and the grading of the reaction., Conclusion: This survey demonstrates that AEs occurring in the setting of DMSO-reduced HPC grafts are directly related to the amount of granulocytes and thus emphasizes the need for high-quality apheresis products so as to improve the safety of HPC infusion.

Background: : Elderly patients with acute myeloid leukemia (AML) have a poor prognosis, which is explained by the disease itself and by host-related factors. The objective of this study was to determine the prognostic role of comorbidities in this population., Methods: : For this single-center, retrospective study, the authors analyzed the outcome of 133 patients aged >/=70 years who received induction chemotherapy for nonpromyelocytic AML between 1995 and 2004. Comorbidities were evaluated by using an adapted form of the Charlson comorbidity index (CCI)., Results: : The median patient age was 73 years. The CCI score was 0 for 83 patients (68%), 1 for 16 patients (13%), and >1 for 23 patients (19%). The complete remission (CR) rate was 56%, and the median overall survival was 9 months. In multivariate analysis, 4 adverse prognostic factors for CR were identified: unfavorable karyotype, leukocytosis >/=30 g/L, CD34 expression on leukemic cells, and CCI >1. A score could be generated to allow the stratification of patients into low-, intermediate-, and high-risk groups with CR rates of 87%, 63%, and 37%, respectively. The risk of early mortality and the probability of survival also were different in the 3 risk groups (P = .02 and P = .01, respectively)., Conclusions: : The results from this study indicated that associated comorbidities are independent factors that may influence achievement of CR in elderly patients with AML. Such a scoring system may be useful in the prognostic staging systems that are used to identify patients with AML who can benefit from induction chemotherapy., ((c) 2007 American Cancer Society.)

Acute lymphoblastic leukemia (ALL) in the elderly is characterized by its ominous prognosis. On the other hand, imatinib has demonstrated remarkable, although transient, activity in relapsed and refractory Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL), which prompted us to assess the use of imatinib in previously untreated elderly patients. ALL patients aged 55 years or older were given steroids during 1 week. Ph+ve cases were then offered a chemotherapy-based induction followed by a consolidation phase with imatinib and steroids during 2 months. Patients in complete response (CR) after consolidation were given 10 maintenance blocks of alternating chemotherapy, including two additional 2-month blocks of imatinib. Thirty patients were included in this study and are compared with 21 historical controls. Out of 29 assessable patients, 21 (72%, confidence interval (CI): 53-87%) were in CR after induction chemotherapy vs 6/21 (29%, CI: 11-52%) in controls (P=0.003). Five additional CRs were obtained after salvage with imatinib and four after salvage with additional chemotherapy in the control group. Overall survival (OS) is 66% at 1 year vs 43% in the control group (P=0.005). The 1-year relapse-free survival is 58 vs 11% (P=0.0003). The use of imatinib in elderly patients with Ph+ ALL is very likely to improve outcome, including OS.

The potential benefit of rituximab as adjuvant to high-dose therapy (HDT) has been investigated in patients under 60 years with poor-risk (age-adjusted international prognostic index at 2-3) CD20+ diffuse large B-cell lymphoma (DLBCL). The treatment consisted of four cycles of high-dose CEOP (cyclophosphamide, epirubicin, vincristine, prednisone), plus etoposide and cisplatin during the two last cycles. Peripheral blood stem cells were collected after cycle 1, and reinfused after cycles 3 and 4. Four weekly rituximab infusions were subsequently delivered. Among the 36 patients included, 30 could complete chemotherapy schedule, and 24/36 received rituximab. A complete response occured in 26/36 patients (72%). With a median follow-up of 30 months, the estimated 5-year overall survival (OS) and event-free survival (EFS) rates (mean +/- s.d.) were 65 +/- 16 and 63 +/- 15%, respectively. For the 24 patients who received both chemotherapy and rituximab, the estimated 5-year OS and EFS rates were 86 +/- 14 and 82 +/- 15%. These data suggest that rituximab after HDT is feasible. Both complete remission rate and survival curves compare favorably with the poor outcome usually observed in high-risk DLBCL patients managed with HDT without rituximab.

Background: Thirty-three patients (median age 52; range 26-60) with acute myeloblastic leukemia (AML) were included in a pilot study of allogeneic stem cell transplantation (Allo-SCT) following a reduced-intensity conditioning (RIC)., Methods: Patients achieving first complete remission (CR1) were selected for their high-risk clinical and/or leukemic features. All patients received two courses of consolidation chemotherapy including one high-dose cytarabine course. Among them, 13 patients in addition received a high-dose melphalan course followed by autologous SCT. Then, all patients received an RIC Allo-SCT combining fludarabine, busulfan, and antithymocyte globulin., Results: All patients engrafted had cumulative incidences of Gluksberg System Grade 2 acute and chronic graft-versus-host-disease (GVHD) of 24 (9-39%) and 64 (48-80%), respectively. Three patients died from nonrelapse causes (NRD) (cumulative incidence: 9%, 95% confidence interval (CI): 0-19) and 6 relapsed (cumulative incidence: 18%, 95% CI: 5-31). With a median follow-up of 18 months (range 7-52) after Allo-SCT, 26 patients are alive, of whom 24 remained in CR1 for a 2-year overall survival and leukemia-free survival (LFS) probabilities of 79 (range 61-90%) and 76 (range 59-87%), respectively. In a 'landmark' analysis starting on Day 100, the occurrence of chronic GVHD was associated with a lower relapse rate (0% vs. 44%: P = 0.007) and improved outcome (LFS; 95% vs. 53%, P = 0.007; overall survival, 95% vs. 61%, P = 0.05)., Conclusions: We conclude that the sequential combination of intensive chemotherapy and allogeneic immunotherapy might offer relatively low NRD and leukemia relapse rates even in high-risk patients., ((c) 2005 American Cancer Society.)

Using a genetic randomization through a 'donor' vs 'no donor' comparison, the aim of this analysis was to assess the real benefit of reduced intensity conditioning allogeneic stem cell transplantation (RIC-allo-SCT) among 95 adult high-risk acute myeloid leukemia (AML) patients. In an 'intention-to-treat' analysis, leukemia-free survival (LFS) was significantly higher in the 'donor' group as compared to the 'no donor' group (P=0.01; 54 vs 30% at 4 years). The latter held true when restricting the analysis to the 25 patients who could actually receive the RIC-allo-SCT (P=0.001). Overall transplant-related mortality in the 'transplant' group was 12%, with overall survival (OS) being significantly higher in the 'transplant' group as compared to the 'no transplant' group (P=0.01). Also, in the 'intention-to-treat' analysis, OS was significantly higher in the 'donor' group as compared to the 'no donor' group (P=0.04). In the multivariate analysis, actual performance of RIC-allo-SCT (P=0.001; RR=4.0; 95% CI, 1.7-9.6) was the strongest factor significantly predictive of an improved LFS. We conclude that if a matched related donor is identified, RIC-allo-SCT should be proposed for AML patients not eligible for standard myeloablative allo-SCT.

Conventional cytogenetic analysis currently stratifies acute myelogenous leukaemia (AML) into prognostically relevant groups. However, approximately 50% of adult AMLs have normal cytogenetics (NC-AMLs), and represent a heterogeneous and poorly understood group. We analysed gene expression in 55 AML samples including 53 cases from adult patients with NC-AML (n = 36), trisomy 8, t(15;17), t(8;21), t(11;19), 7q deletion, and two cell lines using 9000-gene DNA microarrays. Global hierarchical clustering showed that NC-AMLs are a heterogeneous group. Supervised analysis distinguished two subgroups of NC-AML: one subgroup constituted a homogeneous NC cluster ('pure NC-AML'), and the other NC-AMLs were close to the AML cases with translocations ('translocation like'). Gene expression signatures were also derived for patients with trisomy 8, as well as FLT3 and MLL gene duplications. Importantly, samples from 24 NC-AML patients who could be evaluated for clinical outcome were analysed. In all, 43 genes that discriminated two classes of patients with significantly different prognosis were identified. The poor prognosis class contained a majority of 'pure NC-AMLs', whereas the 'translocation-like' AMLs were in the good prognosis class. Discriminator genes included genes involved in drug resistance (TOP2B), protein transport (MTX2, SLC35A2), and cell signalling (MAPK1, PRKAB2). Our results demonstrate the transcriptional heterogeneity of NC-AMLs, and suggest the existence of 'translocation-like' NC-AMLs and of a gene expression signature that may predict response to chemotherapy.

Objective: Acute graft-vs-host disease (aGVHD) remains an important cause of morbidity after reduced-intensity conditioning (RIC) allogeneic transplantation (allo-SCT). It has been shown that antithymocyte globulin (ATG) dose infused during RIC is a major determinant for the likelihood of developing aGVHD. The ATG modulation on aGVHD is likely related to in vivo T-cell depletion., Patients and Methods: We therefore investigated the relationship between the cellular composition of the allograft and clinical outcome in 57 patients who received allogeneic peripheral blood stem cells from HLA-identical siblings following an ATG-based RIC., Results: In a multivariate analysis, the CD8+ T cell dose infused was the only parameter associated with the risk of aGVHD (p=0.031; RR=1.96; 95% CI, 1.1-3.6). When looking at the extremes, patients experiencing grade III-IV aGVHD received a median of 143 x 10(6)/kg CD8+ T cells, while patients without aGVHD received a median of 96 x 10(6)/kg CD8+ T cells (p=0.021). None of the different cell subtypes contained in the allograft was associated with a significant probability of developing chronic GVHD. Patients with grade II aGVHD who received an intermediate dose of CD8+ T cells (median, 111 x 10(6)/kg) had a significantly better overall survival in comparison to patients with grade 0-I or grade III-IV aGVHD (p=0.009)., Conclusion: In comparison to myeloablative allo-SCT, these results demonstrate that a cautious monitoring of the number of cells infused, at least in the context of ATG-based RIC, may represent an important predictive indicator of early transplant-related events and outcome after RIC allo-SCT.

The use of reduced intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (allo-SCT) can result in a significant decrease in early procedure-related toxicity in patients not eligible for standard myeloablative regimens. However, acute graft-versus-host disease (aGVHD) remains a matter of concern after RIC allo-SCT, and its incidence might be expected to be higher in elderly and high-risk patients. This report investigated mycophenolate mofetil (MMF) and cyclosporin A (CsA) combination (n=14) in comparison to CsA alone (n=20) for GVHD prophylaxis in cancer patients aged over 50 years (27 haematological malignancies and seven solid tumours) receiving an HLA-identical sibling antithymocyte-globulin (ATG)-based RIC allo-SCT. Baseline demographic characteristics and risk factors for aGVHD were comparable between both groups. Although MMF administration was not associated with any significant toxicity, the cumulative incidence of any form of GVHD was comparable between both groups (cumulative incidence of grade II-IV aGVHD, 50% (95% CI, 28-72%) for CsA alone, as compared to 64% (95% CI, 39-89%) to CsA and MMF, P=NS), suggesting that adjunction of MMF to CsA is feasible, but does not translate towards a significant reduction of aGVHD, at least in the context ATG-based RIC allo-SCT.

Background: Patients age > or = 75 years with acute myeloid leukemia (AML) generally are offered palliative treatments instead of induction chemotherapy. The authors conducted a retrospective study comparing the outcomes among these elderly patients with the outcomes among younger patients to assess the impact of intensive treatment approaches in this age group., Methods: One hundred ten consecutive patients age > or = 75 years with newly diagnosed AML (excluding patients with acute promyelocytic leukemia) were treated in the authors' center over 10 years. Initial treatment was comprised of anthracycline-based induction chemotherapy (i.e., intravenous idarubicin or daunorubicin for 3 days plus cytarabine [ARAC] for 7 days [3 + 7 regimen] or oral idarubicin) for 62 patients (56%), antimetabolite-based chemotherapy (including low-dose ARAC, oral 6-mercaptopurine plus methotrexate, or hydroxyurea) for 40 patients (36%), and supportive care only for 8 patients (7%). Results were compared with the results from 200 patients ages 65-74 years who were treated during the same period., Results: A complete response (CR) to anthracycline-based induction therapy was achieved by 23 of 62 patients (37%), and the 2-year overall survival rate was 22% (which was not statistically different from the group of patients ages 65-74 years). In a multivariate analysis of the entire study group (310 patients), treatment (anthracycline-based vs. other) and age as continuous variable were found to affect survival significantly. In a Landmark analysis, the achievement of a CR translated into improved survival in patients age > or = 75 years., Conclusions: Patients age > or = 75 years should not be excluded systematically from intensive chemotherapy regimens. Decisions should be based on stratification systems that include functional status and comorbidity assessments as well as prognostic factors, such as cytogenetics., (Copyright 2004 American Cancer Society.)

In all, 41 multiple myeloma (MM) patients received an antithymocyte globulin (ATG), fludarabine, and busulfan-based reduced intensity conditioning (RIC) for allogeneic stem cell transplantation (allo-SCT) from HLA-identical siblings. In total, 29 patients (70%) were in partial remission, one patient in complete remission, and 11 (27%) with progressive disease at the time of allo-SCT. Median time between diagnosis and allo-SCT was 24 months. The cumulative incidences of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) were 36% (95% CI, 21-51%) and 7% (95% CI, 2-20%), respectively. Overall, 10 patients developed limited chronic GVHD, whereas seven developed an extensive form (cumulative incidence, 41% (95% CI, 26-56%) at 2 years). With a median follow-up of 389 days, the overall cumulative incidence of transplant-related mortality (TRM) was 17% (95% CI, 6-28%). In all, 11 patients (27%) are in continuous complete remission, and the Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) at 2 years were 62% (95% CI, 47-76%) and 41% (95% CI, 23-62%), respectively. PFS and OS were significantly higher in patients with chronic GVHD as compared to patients without chronic GVHD (P=0.006 for PFS and P=0.01 for OS). Collectively, these data demonstrate that RIC allo-SCT can mediate a potentially curative graft-versus-myeloma effect with an acceptable incidence of toxicity and TRM.

In the setting of reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (allo-SCT), the epidemiology of transplant-related infections is still poorly defined. In 101 high-risk patients who received an HLA-identical sibling allo-SCT after RIC, including fludarabine, busulfan and antithymocyte globulin (ATG), we report during the first 6 months a cumulative incidence of positive CMV antigenemia of 42% (95% CI 32-52%), developing at a median of 37 (range 7-116) days without evidence of CMV disease (median follow-up, 434 days). The cumulative incidence of bacteremia was 25% (95% CI 17-33%), occurring at a median of 67 (range 7-172) days, while patients had recovered a full neutrophil count. In all, 65% of the bacteremia (95% CI 49-81%) were gram negative. The cumulative incidence of fungal infections was 8% (95% CI 3-13%), with a median onset of 89 (range 7-170) days. In multivariate analysis, stem cell source (bone marrow; P=0.0002) was significantly associated with the risk of positive CMV antigenemia, while higher doses of prednisone (>2 mg/kg) represented the major risk factor for bacteremia (P=0.0001). Infectious-related mortality was 5% (95% CI 1-9%), with aspergillosis being the principal cause. Collectively, these results suggest that prospective efforts are warranted to develop optimal antimicrobial preventive strategies after RIC allo-SCT.

Objective: Reduced-intensity conditioning regimens (RIC) and peripheral blood stem cells (PBSC) are increasingly used for allogeneic stem cell transplantation (allo-BMT). RIC has been shown to allow engraftment with minimal early transplant-related mortality (TRM). However, in the context of RIC, the use of bone marrow (BM) as stem cell source is still little evaluated., Patients and Methods: In this report, we analyzed the outcome of 32 high-risk patients with hematological malignancies who received an HLA-identical sibling allo-BMT after RIC including fludarabine, busulfan, and anti-thymocyte globulin (ATG)., Results: Sustained neutrophil and platelet recovery occurred at a median of 13 days (range, 10-19) and 17 days (range, 0-45) respectively. Early and durable full donor chimerism could be established as soon as the first month after allo-BMT. Also, a sustained and early CD8(+) T-cell recovery was observed, but the CD4(+) T-cell compartment remained profoundly low. The cumulative incidences of grade II-IV acute GVHD and chronic GVHD were 26% (95% CI, 11-41%) and 31% (95% CI, 15-47%) respectively. The overall cumulative incidence of TRM was 28% (95% CI, 12-44%) occurring mainly in patients aged over 50. In this setting, GVHD showed a protective effect on disease progression or relapse with better progression-free survival for patients with GVHD as compared to patients without GVHD (p=0.03)., Conclusions: Collectively, these results confirm that the use of BM grafts for RIC is feasible with durable donor engraftment and no detrimental GVHD.

Reduced-intensity conditioning (RIC) regimens are increasingly used for allogeneic stem cell transplantation (allo-SCT). RIC has been shown to allow engraftment with minimal early transplantation-related mortality (TRM). However, in the context of RIC, predictive factors for acute and chronic graft-versus-host disease (aGVHD and cGVHD, respectively) and their effect on outcome remain unknown. In this report, we analyzed the outcome of 101 high-risk patients (70 hematologic and 31 nonhematologic malignancies) who received an HLA-identical sibling allo-SCT after RIC, including fludarabine, busulfan, and antithymocyte globulin (ATG). The cumulative incidence of grade II-IV aGVHD was 36% (95% confidence interval [CI], 27%-45%), whereas the cumulative incidence of cGVHD at 2 years was 43% (95% CI, 33%-53%). In multivariate analysis, the incidence of aGVHD was significantly associated with the ATG dose infused during conditioning (P =.0005), whereas peripheral blood as stem cell source was the only predictive factor for the development of cGVHD (P =.0007). The 1-year cumulative incidences of disease progression or relapse in patients with (n = 69) and without (n = 31) GVHD (whatever its form or grade) were 30% (95% CI, 19%-41%) and 55% (95% CI, 37%-72%), respectively (P =.02), suggesting that a potent graft-versus-tumor (GVT) effect can be achieved in high-risk patients following RIC. Moreover, the GVT effect was closely associated with GVHD without an increased risk of TRM (cumulative incidence of TRM, 18% [95% CI, 10%-25%]). Collectively, these results provide a framework for the refinement of RIC approaches designed to enhance the GVT effect with an acceptable risk of GVHD.

True histiocytic lymphoma (THL) is a very rare type of non-Hodgkin's lymphoma (NHL) in which neoplastic cells exhibit markers of histiocytic differentiation. Some cases of THL have been reported in patients with previous acute lymphoblastic leukaemia (ALL), especially in children and young adults, in whom the acute leukaemia was of T-cell origin. The relationship between the initial lymphoid tumour and the secondary THL remains unclear, as a common monoclonal origin shared by both neoplasms has never been definitively demonstrated. We report a patient with B-ALL who developed a nodal and extranodal tumour with histological and immunohistochemical features of THL 4 years after the initial diagnosis. Genotypic study showed that both neoplasms contained the same immunoglobulin heavy gene rearrangement, which has not been reported previously.

We are entering an exciting era in the management of chronic myeloid leukemia (CML). This, in part is related to our considerable understanding of the molecular lesion associated with the disease-arguably the best characterized of any malignancy. Although allogeneic hematopoietic cell transplantation remains the sole potentially curative therapy at present, newer agents such as the tyrosine kinase inhibitor STI571 show promise and may eventually replace less specific cytotoxic therapy. This review focuses on the numerous options currently available for treating CML and includes a treatment algorithm.

It is now established that a subgroup of non-Hodgkin's lymphoma (NHL) patients probably benefit from high-dose therapy (HDT). We therefore retrospectively analyzed survival of 126 consecutive patients with large cell lymphoma (LCL) and high-intermediate (HI) or high-risk (H) age-adjusted international prognostic index (Aa-IPI). They received either standard chemotherapy (CT) (66 patients), or HDT (60 patients). Distribution of the Aa-IPI scores showed no statistical significant difference between the two treatment groups. Complete response (CR) rate was 51% for the whole series, with 41% and 62% for the standard CT group and HDT group, respectively. With a median follow-up of 63 months (range, 16 to 159), the 5-year overall survival (OS) and event-free survival (EFS) for all patients was 52% and 43%, respectively. There was a statistical significant difference in terms of survival towards the HDT group: OS at 76% vs 31%, EFS at 64% vs 24%. Patients who achieved CR with front-line therapy had a 5-year OS at 70%, while it was 34% for patients who were not in CR. These results are comparable to those reported in the literature, and strongly suggest that both initial CR achievement and HDT as front-line treatment are predictive factors for prolonged survival of patients with poor-risk LCL. Bone Marrow Transplantation (2000) 25, 35-40.

We have conducted a phase II outpatient trial testing weekly oral administration of idarubicin (ZAVEDOS-ZVD) alone to determine the rate of objective response and toxicity in poor risk acute myeloid leukemia (AML) patients over 60 years of age. The treatment consisted of three phases: induction, with 20 mg/m2 of ZVD on days 1, 8, 15 and 22; consolidation with 20 mg/m2 of ZVD for 4 weeks; and maintenance with six cycles lasting 3 months and consisting of oral 6 mercapto-purine 2 mg/kg/day, 4 days a week for 2 months; subcutaneous cytarabine 1 mg/kg, once a week for 2 months; and oral ZVD 20 mg/m2 on day 1 and day 8 of the third month. In case of failure after induction course, patients received salvage treatment with 4 weekly oral doses of 40 mg/m2 ZVD. Fifty-one patients with a median age of 76 years were enrolled and could receive induction course. Of these 51 patients, 37 could receive subsequent courses, which consisted either of consolidation, or salvage. Only 11 patients underwent maintenance treatment. Sixty-three percent of patients had to be hospitalized during induction, for a median duration of 14.5 days, and 87% required hospitalization during salvage for a median duration of 17.5 days. Only five patients (38%) required hospitalization during consolidation. There were three toxic deaths (6%), two from hemorrhage and one from pulmonary embolism. The overall response rate was 29%, with 12 patients in complete response (25%) and two in partial response (4%). The median overall survival rate is 4 months for the whole population, and the median DFS is 9.6 months among the 14 responding patients. The results of this trial show that this new weekly schedule of oral ZVD chemotherapy is feasible and effective in poor risk elderly patients with AML. This regimen may be helpful for patients unable to tolerate intensive intravenous regimens, and is a real alternative to palliative treatments.