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Forty patients with relapsed diffuse large B cell lymphoma (DLBCL) autografted in partial response (PR) (n = 23) or in refractory relapse (RR) (n = 17) achieved complete remission (CR) after autologous stem cell transplantation (ASCT). Salvage treatment consisted of ifosphamide, epirubicin and etoposide (IEV) in 33 patients and Cisplatinum, ARA-C and dexamethasone (DHAP) in 7 patients. All PR and 8 RR patients were conditioned with BEAM, while 9 RR cases received the BCV regimen. There were no significant differences between the two groups as age, serum LDH, duration of CR1 and IPI at relapse are concerned. Relapse rate after ASCT was 39% in PR group as opposed to 88% in RR group (p = 0.003). Median relapse free survival from ASCT was 6 months for RR patients as opposed to 34 months for PR patients (p = 0.003); median overall survival from ASCT was 10 months for RR subset as opposed to not reached for RR subgroup (p = 0.001). These data demonstrate that CR achieved after ASCT in DLBCL patients who are refractory to previous salvage therapy does not result in long-term disease control. Alternative preparative regimens, allogeneic SCT and/or monoclonal antibodies in the post-ASCT phase should be considered for RR patients despite CR achievement. Copyright © 2006 John Wiley & Sons, Ltd.

Objectives : To evaluate therapeutic results and prognostic factors from a series of 44 patients affected by de novo acute myeloid leukemia with multilineage dysplasia (MD-AML), treated with the combination of fludarabine, cytarabine and G-CSF (FLAG). Methods : Forty-four patients with de novo MD-AML were treated with the FLAG regimen. The median age was 61 yr (range 31–75 yr). Induction therapy consisted of the FLAG regimen; consolidation included idarubicin plus cytarabine. Patients with a compatible donor and aged less than 55 yr were programmed to receive allogeneic bone marrow transplantation (BMT), while in those without a donor and aged less than 65 yr autologous transplantation with peripheral blood stem cells mobilized by a consolidation regimen plus G-CSF was planned. Bone marrow harvest was performed in poor mobilizers. Results : Complete remission (CR) was achieved in 28 out of 44 patients (64%). Death in induction occurred in four patients (9%), while 12 patients (27%) were resistant to FLAG. Toxicity of consolidation was negligible. Most patients aged less than 60 yr and achieving CR were eligible for transplantation procedures, the main reason of exclusion being early relapse. Median overall survival and disease free survival were 16 and 22 months, respectively. Unfavorable cytogenetics was the only parameter significantly related to inferior clinical outcome following multivariate analysis. Conclusion : Multilineage dysplasia per se is not an adverse prognostic factor in AML patients treated with the FLAG regimen. Favorable results are obtained in patients with intermediate karyotype, while in those with adverse cytogenetics new approaches are clearly needed. The toxicity of the regimen is also acceptable in the elderly, and following induction/consolidation, most patients may be submitted to transplantation procedures.

The clinical course of thrombotic thrombocytopenic purpura has dramatically improved after the introduction of plasma-based therapy, including plasma exchange and plasma infusion. However, a considerable number of patients still experience relapse after initial successful treatment. In this study, vincristine (VCR) was given as salvage treatment in 12 episodes of recurrent thrombotic thrombocytopenic purpura in seven patients, concomitantly with short-term plasma infusion. Complete remission (CR) was defined by normal platelet, hemoglobin, and serum lactic dehydrogenase (LDH) values as well as by absence of clinical signs. Of 12 patients, 12 achieved CR following therapy with VCR. The median duration of CR was 15 months (range: 2-16). Toxicity was mild consisting of paresthesias in three cases, leukopenia in one case, and autonomic neuropathy leading to paralytic ileus in one case. We conclude that VCR is remarkably effective for recurrent thrombotic thrombocytopenic purpura with acceptable toxicity.

Background: Conflicting results have been reported about the prognostic relevance of antecedent myelodysplastic syndrome (MDS) in acute myeloid leukemia (AML) of older adults. Patients and methods: Data from 87 intensively treated AML patients (median age 69 years) were analyzed, with the aim of comparing therapeutic results and toxicity between de novo and AML secondary to a previous MDS (s-AML). Rate of CD34+ cells mobilization and feasibility of autologous stem cell transplantation (ASCT) were also compared. Results: Complete remission rate, death in induction and primary resistance were not statistically different between the two groups. Median time for neutrophil recovery was similar, while s-AML patients required a longer time for platelet recovery (P = 0.04). There was no difference as to eligibility for consolidation as well as for mobilization and feasibility of ASCT. S-AML had negligible impact on overall survival (OS) and disease-free survival (DFS). In the multivariate analysis the only parameter significantly related to either OS or DFS duration was adverse karyotype (P = 0.02 and 0.04, respectively). Conclusions: A diagnosis of s-AML does not represent a clinically relevant prognostic factor in elderly AML patients treated with aggressive therapy. Furthermore, s-AML patients can be mobilized and autografted with comparable results as opposed to de novo cases.

Fetal liver tyrosine kinase 3 (FLT3) mutations represent a powerful prognostic indicator in acute myeloid leukemia (AML). Further, interaction between FLT3 and its ligand plays a role in normal hematopoiesis. Accordingly, FLT3 mutations may affect mobilization of peripheral blood stem cells (PBSCs) and feasibility of autologous stem cell transplantation (ASCT) in AML. We analyzed the effect of FLT3 mutations on mobilization of CD34(+) cells and on PBASCT feasibility from 111 patients with AML, with a median age of 58 years and normal karyotype. Overall, 23 patients (21%) had FLT3 mutations. The complete remission rate was 74% and was not influenced by FLT3 mutations (73% for patients with FLT3(-) and 78% for those with FLT3(+); P = .78). The successful mobilization rate was 79% and was comparable for patients with FLT3(-) and with FLT3(+) (P = .42). Median numbers of CD34(+) cells collected were 7.6 x 10(6)/kg and 7.1 x 10(6)/kg for patients with FLT3(-) and those with FLT3(+), respectively (P = .64). Among 73 patients evaluated for mobilization, feasibility of ASCT was 71%, and there was no difference between patients with FLT3(-) (74%) and those with FLT3(+) (61%), P = .43. We conclude that the FLT3 mutations have no influence on mobilization of CD34(+) cells or on feasibility of PBASCT in patients with AML and normal karyotype. (C) 2006 American Society for Blood and Marrow Transplantation.

Introduction: Between 30 and 50% of patients with acute myeloid leukemia still relapse after autologous stem cell transplantation. We investigated the feasibility of a new conditioning regimen consisting of high dose IDA plus oral busulphan in patients undergoing autologous transplantation. Materials and methods: Patients (n=13) were given three days continuous infusion IDA, followed by four days conventional dose oral busulphan as conditioning. Peripheral blood stem cells were used in all cases. Eleven patients were in CR1. Patients with t(8;21) and inv(16) as well as those with acute promyelocytic leukemia were excluded from the study. The median of CD34 + cells infused was 6.2610 6 /l (2.6‐16.1). Results: No case of transplant-related mortality occurred. The median number of days to neutrophil (40.5610 9 /l) and platelet (420610 9 /l) recovery was 10 (7‐21) and 20 (9‐26), respectively. Patients needed a median of 3 platelet units (1‐6) and 3 blood units (0‐12), respectively. Left ventricular ejection fraction remained unmodified after ASCT. Twelve out of 13 patients (92%) had variable grade of mucositis (two grade 2, five grade 3 and five grade 4). Total parenteral nutrition was needed in nine patients (69%). After a median follow-up of 14 months from ASCT, 11 patients out of 13 (85%) are alive in continuous CR; the other two patients experienced relapse at 12 and 14 months. Conclusion: Our data demonstrate the feasibility of a conditioning regimen based on highdose IDA plus Busulphan in AML. Results concerning antileukemic eAcacy are promising, but need confirmation on larger series with longer follow-up. The Hematology Journal (2001) 2, 214‐219

Several studies have shown that therapy-related MDS (tMDS) and AML (tAML) have a poor outcome with very few long-term survivors. Curative treatment strategies are not yet standardized and the role of hematopoietic stem cell transplantation (SCT) is still not fully elucidated in standard care treatment. We performed a retrospective outcome research with the aim of looking at the survival curves of tMDS and tAML patients treated at 7 different Institutions. According to the presence of comorbidities or a matched donor, 71 patients (pts) received the best treatment option based on attending physician opinion: 24 pts (group A) with tAML (n=13, FAB M0, M1, M2, M4) and tMDS (n=7 RAEB-2. n=4 RAEB-1) received allogeneic transplantation, 28 pts (group B) with tAML (n=20, FAB M0, M1, M2, M4, M5) and tMDS (n=3 RAEB-2, n=4 RAEB-1, n=1 RA) received chemotherapy and 19 pts (group C) received supportive care only (n=1 tAML, n=18 low-risk MDS or RAEB-1 (n=5)). Median age was 55 years (range 23–67) in group A, 61 years (range 27–73) in group B and 55 years (range 22–70) in group C. Conventional karyotype analysis was available in 12 pts of group A (n=7 complex, n=1 normal, n=2 isolated del(7q) or monosomy 7, n=1 isolated del(5q), n=1 trisomy 21) and in 15 pts of group B (n=3 complex, n=8 normal, n=1 isolated del(Y), n=1 isolated del(11), n=1 isolated trisomy 11, n=1 isolated trisomy 8). In the group A, all pts, because of age and/or comorbidities, received a fludarabine-based reduced-intensity conditioning followed by allogeneic peripheral blood SCT. Disease status at transplant was categorized as low risk (n=9 CR1 or CR2), high risk (n=3 PR, n=6 PD, n=2 refractory) and 4 pts were treated up-front. The median time from diagnosis to allografting was 6 months (range: 1–80 months). Pts received allogeneic stem cells from HLA-matched siblings (n=16), or HLA-matched unrelated donors (n=6), or haploidentical related donors (n=2). All pts engrafted. Acute GVHD grade II–IV occurred in 6 pts (n=1 post-DLIs), chronic GVHD developed in 6 pts (n=1 post-DLIs). OS at 5 years was 5.5%, the 4-year EFS was 0%, TRM at 100 days and at 1 year were 28%. No statistical differences were observed in TRM, EFS, and OS according to disease status at transplant and diagnosis of tMDS or tAML. DFS for pts in CR at transplant was 23% at 1 year. In the group B, pts received chemotherapy and 11 of them an autologous stem cell transplantation. OS at 5 years was 16%, EFS at 5 years was 10%, DFS at 1 year was 31%. TRM at 5 years was 30%. In the group C, OS was 28% at 5 years. Our data show that, in daily clinical practice, the outcome of patients receiving chemotherapy followed by allogeneic SCT is not improved compared to the patients not having a suitable donor. At the present time, considering the very low chance of cure, in therapy-related disorders the main goal for clinicians should be prevention.