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The use of post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis is not established after reduced intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) from fully matched donors. This was a randomized, open-label, multicenter, phase 2 trial. All patients received a RIC regimen with fludarabine, intravenous busulfan for 2 days (Flu-Bu2), and a peripheral blood stem cell (PBSC) graft from a matched related or 10/10 HLA-matched unrelated donor. Patients were randomly assigned to receive anti-thymocyte globulin (ATG) 5 mg/kg plus standard GVHD prophylaxis or PTCy 50 mg/kg/d at days +3 and +4 plus standard GVHD prophylaxis. The primary endpoint was the composite endpoint of GVHD- and relapse-free survival (GRFS) at 12 months after HSCT. Eighty-nine patients were randomly assigned to receive either PTCy or control prophylaxis with ATG. At 12 months, disease-free survival was 65.9% in the PTCy group and 67.6% in the ATG group (P = 0.99). Cumulative incidence of relapse, non-relapse mortality, and overall survival were also comparable in the two groups. GRFS at 12 months was 54.5% in the PTCy group versus 43.2% in the ATG group (P = 0.27). The median time to neutrophil and platelet count recovery was significantly longer in the PTCy group compared to the ATG group. Except for day +30, where EORTC QLQ-C30 scores were significantly lower in the PTCy compared to the ATG group, the evolution with time was not different between the two groups. Although the primary objective was not met, PTCy is effective for GVHD prophylaxis in patients receiving Flu-Bu2 conditioning with a PBSC graft from a fully matched donor and was well tolerated in term of adverse events and quality of life. This trial was registered at clinicaltrials.gov: NCT02876679., (© 2024. The Author(s).)

Population-based studies and case reports suggest that there may be an increased risk of acute leukemia associated with sickle cell disease (SCD). Following the description of a new case report, an extensive review of the literature identified 51 previously described cases. Most cases study showed myelodysplastic features confirmed, when available, by genetic markers such as chromosome 5 and/or chromosome 7 abnormalities and TP53 gene mutations. The increased risk of leukemogenesis is certainly multifactorial and related to the pathophysiologic mechanisms of the clinical manifestations of SCD. Chronic hemolysis and secondary hemochromatosis may cause increased chronic inflammation, resulting in persistent marrow stress, which could potentially compromise the genomic stability of the hematopoietic stem cells generating genomic damage and somatic mutations over the course of SCD and its treatment, resulting in a clone that led to acute myeloid leukemia., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Relapsed B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic stem cell transplantation (allo-HCT) still represents a major concern with poor outcomes. The aim of this study is to compare the efficacy and safety of blinatumomab and donor lymphocyte infusion (DLI) versus blinatumomab alone in this setting. This is a multicenter retrospective study from centers of SFGM-TC. All transplanted patients who received blinatumomab salvage therapy were included. Patients who received DLI from 1 month before to 100 days after the starting of blinatumomab were included in the blina-DLI group. Seventy-two patients were included. Medium follow-up was 38 months. Fifty received blinatumomab alone and 22 the association blinatumomab-DLI. Two-year overall survival (OS) was 31% in the blinatumomab group and 43% in the blinatumomab-DLI group (p = 0.31). Studying DLI as a time dependent variable, PFS did not significantly differ between the 2 groups (HR:0.7, 95% CI: 0.4-1.5). In multivariate analysis, DLI was not a prognostic factor for OS, progression-free survival and progression/relapse incidence. Adverse events and graft-versus-disease rates were comparable in the 2 groups. In conclusion, adding DLI between 1 month before and 100 days after start of blinatumomab is safe and does not seem to improve outcomes in B-ALL patients who relapsed after allo-HCT., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

In order to identify cytomegalovirus (CMV)-seropositive patients who are at risk of developing CMV infection following first allogeneic hematopoietic cell transplantation (allo-HCT), we built up a scoring system based on patient/donor characteristics and transplantation modalities. To this end, 3690 consecutive patients were chronologically divided into a derivation cohort (2010-2012, n = 2180) and a validation cohort (2013-2014, n = 1490). Haploidentical donors were excluded. The incidence of first clinically significant CMV infection (CMV disease or CMV viremia leading to preemptive treatment) at 1, 3, and 6 months in the derivation cohort was 13.8%, 38.5%, and 39.6%, respectively. CMV-seropositive donor, unrelated donor (HLA matched 10/10 or HLA mismatched 9/10), myeloablative conditioning, total body irradiation, antithymocyte globulin, and mycophenolate mofetil significantly and independently affected the incidence of 3-month infection. These six factors were selected to build up the prognostic model. Four risk groups were defined: low, intermediate-low, intermediate-high, and high-risk categories, with a 3-month predicted incidence of first clinically significant CMV infection in the derivation cohort of 22.2%, 31.1%, 45.4%, and 56.9%, respectively. This score represents a framework for the evaluation of patients who are at risk of developing clinically significant CMV infection following allo-HCT. Prospective studies using this score may be of benefit in assessing the value of anti-CMV prophylaxis in well-defined patient cohorts.

Ninety-four adults with newly diagnosed or relapsed/refractory acute myeloid leukemia (AML) were treated with fractionated doses of gemtuzumab ozogamicin (GO) at one-single French center over ten years. We attempted to define predictive factors for response and survival. The overall response rate was 70% (86% in newly diagnosed and 65% in relapsed/refractory AML). Mortality during induction was 6%. Disease-free survival (DFS) and overall survival at three years after GO treatment was 36% and 31%, respectively. Median DFS in relapsed/refractory patients was eight months with a 3-year DFS at 34%. Among remitters, allogeneic hematopoietic stem cell transplantation (HSCT) can be performed in 28 cases (42%), including two patients in first-line therapy and 26 in further line. In relapsed/refractory patients undergoing allogeneic HSCT after responding to GO therapy, the median DFS was not reached. Incidences of transplant-related mortality, grade ≥ 3 acute graft-versus-host (GvH) disease, and extensive chronic GvH disease were 11%, 14%, and 25%, respectively. No sinusoidal obstruction syndromes were reported among allografted patients as among the other patients in the studied cohort. GO-based chemotherapy is a viable option for the treatment of relapsed/refractory AML patients and is a feasible schedule as a bridge to allogeneic transplant., Competing Interests: Competing interests: The authors declare no conflict of Interest.

Several approaches have been developed to overcome historical barriers associated with poor outcomes in the setting of HLA-haploidentical allogeneic transplantation (HaploSCT). Here, we examine the outcome of patients with various hematological disorders undergoing HaploSCT with high-dose, post-transplantation cyclophosphamide. We performed a retrospective study on 381 patients from 30 centers between January 2013 and December 2015. At the last follow-up, a total of 1058 infectious episodes were diagnosed, affecting 90.3% of the cohort. Median time to first infection was 13 days for bacterial, 32 days for viral and 20 days for fungal infections. Around 41% of these infections were of bacterial origin and 35% of viral origin, among which 48.8% of patients presented CMV reactivation. Median of GVHD relapse-free survival, progression-free survival and overall survival were 7.1 months, 19.9 months and 33.5 months, respectively. HSCT procedure was the primary or contributing cause of death (55.6%), followed by relapse of the original disease (34.2%). Infections accounted for 45.7% of the HSCT-related deaths. The present multicenter data on a large cohort of patients receiving HaploSCT with PTCy confirmed the feasibility of the procedure with an acceptable incidence of infectious complications, not different as compared to other haploidentical platforms or HLA-matched transplantation.

Introduction: Secondary acute myeloid leukemia (sAML) remains a therapeutic challenge. In elderly patients with AML, it is unclear whether sAML displays an inferior outcome compared with de novo AML., Patients and Methods: We studied AML with an antecedent of hematologic disease, treatment-related AML, or AML occurring concurrently to another malignancy in a single-center cohort of patients aged 70 and older with AML. The study included 169 patients who were compared with a cohort of patients with de novo AML, without any prior history of malignant disorders, seen during the same period of time., Results: Hematologic antecedents or presence of prior/concurrent solid malignancy did not impact complete remission rates and overall survival. In multivariate analysis, sAML appeared without independent prognostic value in the elderly., Conclusion: Our results support that sAML and de novo AML in elderly patients are not prognostically distinct entities. They should therefore not be considered separately when investigating outcomes and new treatment strategies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Importance: Pathogen reduction of platelet concentrates may reduce transfusion-transmitted infections but is associated with qualitative impairment, which could have clinical significance with regard to platelet hemostatic capacity., Objective: To compare the effectiveness of platelets in additive solution treated with amotosalen-UV-A vs untreated platelets in plasma or in additive solution in patients with thrombocytopenia and hematologic malignancies., Design, Setting, and Participants: The Evaluation of the Efficacy of Platelets Treated With Pathogen Reduction Process (EFFIPAP) study was a randomized, noninferiority, 3-arm clinical trial performed from May 16, 2013, through January 21, 2016, at 13 French tertiary university hospitals. Clinical signs of bleeding were assessed daily until the end of aplasia, transfer to another department, need for a specific platelet product, or 30 days after enrollment. Consecutive adult patients with bone marrow aplasia, expected hospital stay of more than 10 days, and expected need of platelet transfusions were included., Interventions: At least 1 transfusion of platelets in additive solution with amotosalen-UV-A treatment, in plasma, or in additive solution., Main Outcomes and Measures: The proportion of patients with grade 2 or higher bleeding as defined by World Health Organization criteria., Results: Among 790 evaluable patients (mean [SD] age, 55 [13.4] years; 458 men [58.0%]), the primary end point was observed in 126 receiving pathogen-reduced platelets in additive solution (47.9%; 95% CI, 41.9%-54.0%), 114 receiving platelets in plasma (43.5%; 95% CI, 37.5%-49.5%), and 120 receiving platelets in additive solution (45.3%; 95% CI, 39.3%-51.3%). With a per-protocol population with a prespecified margin of 12.5%, noninferiority was not achieved when pathogen-reduced platelets in additive solution were compared with platelets in plasma (4.4%; 95% CI, -4.1% to 12.9%) but was achieved when the pathogen-reduced platelets were compared with platelets in additive solution (2.6%; 95% CI, -5.9% to 11.1%). The proportion of patients with grade 3 or 4 bleeding was not different among treatment arms., Conclusions and Relevance: Although the hemostatic efficacy of pathogen-reduced platelets in thrombopenic patients with hematologic malignancies was noninferior to platelets in additive solution, such noninferiority was not achieved when comparing pathogen-reduced platelets with platelets in plasma., Trial Registration: clinicaltrials.gov Identifier: NCT01789762.

The treatment of very elderly patients (≥70 years) with acute myeloid leukemia remains controversial. We present here 302 patients seen over a 14-year period in order to understand the real-world treatment patterns and outcomes in this patient population. Less than 25% of patients achieved a complete remission. The median overall survival was 12.4, 11.5 and 2.6 months, with a 3-year rates of 27%, 17% and 6%, for non-acute promyelocytic leukemia patients receiving intensive chemotherapy, lower-intensity therapy or best supportive care (BSC), respectively. In all ages, results were not significantly different among patients receiving low-intensity therapy and intensive chemotherapy, but significantly worse in those treated with BSC only. Similarly, intensive chemotherapy and low-intensity therapy gave better survival rates than BSC in patients with favorable- or intermediate-risk cytogenetics and in those with unfavorable cytogenetics (p < 0.0001 and p = 0.04, respectively).

In the absence of an HLA matched familial donor, a search for an unrelated donor or cord blood unit is initiated through worldwide registries. Although a first look-up on available HLA information of donors in the "book" at BMDW (Bone Marrow Donor Worldwide) can provide a good estimation of the number of compatible donors, the variety of resolution typing levels requires confirmatory typing (CT) which are expensive and time consuming. In order to help recipient centers in their work. The French donor registry (France Greffe de Moelle/Agence de la Biomedecine) has recently developed a software program called "EasyMatch®" that uses haplotype frequencies to compute the likelihood of phenotypic match in donors according to various typing resolution levels. The goal of our study is to report a single monocentric user-experience with EasyMatch®, demonstrating that its routine use reduced the cost and the delay of the donor search in our center, allowing the definition of a new strategy to search compatible unrelated donors. The strategy was first established on a retrospective cohort of 217 recipients (185 adults and 32 children=before score) and then validated on a prospective cohort of 171 recipients (160 adults and 11 children=after score). For all patients, we calculated the delay between the registration day and the donor identification day, and the number of CT requested to the donor centre. Considering both groups, we could observe a significant decrease of the number of CT from 8 to 2 (p<0,001), and a significant decrease of the median delay to identify a suitable donor from 43 to 31days (p<0.0001). EasyMatch® estimates the number of potentially identical donors, but doesn't foresee availability of the donors. It provides us an easy tracking of mismatches, an estimation of the number of potential donors, the selection of population following ethnic origin of patients and a high prediction when probability is high or low. It affords a new approach of donor search in our daily work and improves the efficiency in the great challenge of the compatible donor identification., (Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Objectives: Low-dose cytarabine (LD-AraC) is still regarded as the standard of care in elderly patients with acute myeloid leukemia (AML) 'unfit' for intensive chemotherapy. In this study, we reported our experience with LD-AraC in patients ≥ 70 years old and compared the results to those of intensive chemotherapy, best supportive care (BSC), or hypomethylating agents in the same age population., Methods: Between 2000 and 2014, 60 patients received LD-AraC at 20 mg once or twice daily by subcutaneous injection for 10 consecutive days every 4-6 weeks., Results: Complete remission rate with LD-AraC was 7% versus 56% with intensive chemotherapy and 21% with hypomethylating agents. Median overall survival (OS) of patients treated with LD-AraC was 9.6 months with 3-year OS of 12%. Survival with LD-AraC was better than with BSC only (P = 0.001). Although not statistically significant, intensive chemotherapy and hypomethylating agents tended to be better than LD-AraC in terms of OS (median: 12.4 months and 16.1 months, respectively). There was no clear evidence that a beneficial effect of LD-AraC was restricted to any particular subtype of patients, except for cytogenetics. There was a trend for a better OS in LD-AraC treated patients in the setting of clinical trials as compared with those treated outside of a clinical trial., Conclusions: Despite a trend in favor of intensive chemotherapy and hypomethylating agents over LD-AraC, no real significant advantage could be demonstrated, while LD-AraC showed a significant advantage comparatively to BSC. All this tends to confirm that LD-AraC can still represent a baseline against which new promising agents may be compared either alone or in combination.

Graft-versus-host disease (GVHD) is a known risk factor for invasive aspergillosis (IA), but remains poorly studied in relation to Clostridium difficile infection (CDI). We report a case of a 58-years-old patient who developed an IA within a protected room, CDI and GVHD after allogeneic allogeneic peripheral blood stem cell transplantation (PBSCT). Factors associated with this complex condition in patients receiving allogeneic PBSCT need to be identified., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

We studied the outcome of 213 patients who received allo-HSCT for hematological malignancies, 121 (57%) from HLA identical siblings, 63 (29%) from 10/10 HLA identical unrelated donors and 29 (14%) from 9/10 HLA mismatched unrelated donors. Engraftment was lower in the 9/10 HLA group (90%) than in the 10/10 HLA group (95%) than in the sibling group (99%); 3 months CI of aGVHD ≥ 2 was 32% (23-41), 20% (15-26) and 27% (23-32) respectively; the one year CI of extensive cGVHD was 21% (13-30), 9% (5-13) and 17% (14-21) respectively. The median OS was 10 months (5-21), 18 months (11-NR) and 60 months (31-NR) respectively with 2-years probability of 19% (8-44), 43% (31-59) and 63% (54-74) respectively. TRM was significantly higher in the 9/10 HLA group with 1 year CI of 45% (35-55), compared to 33% (27-39) in the unrelated 10/10 HLA group and 12% (9-15) in the identical siblings group (p < 0.001).

We prospectively evaluated in high-risk myeloma patients the efficacy and toxicity of tandem autologous hematopoietic stem cell transplantation (auto-HSCT) followed by reduced-intensity conditioning (RIC) and allogeneic (allo)-HSCT with bortezomib and donor lymphocyte infusions introduction after allo-HSCT (group 1). Results were compared with results from tandem auto-RIC-allo-HSCT without bortezomib (group 2). Groups 1 and 2 were compared to matched patients not receiving allo-HSCT from the Intergroupe Francophone du Myélome prospective studies. Allo-HSCT groups included 25 patients (12 in group 1, 13 in group 2). All patients engrafted. There were 8 acute GVHD (7 grade II [3 in group 1], 1 grade III in group 1)] and 11 chronic GVHD (3 limited [in group 1], 8 extensive [1 in group 1]). Matched population included 36 controls for group 1 and 39 for group 2. After a median follow-up of 55 months (range, 3-142 months), median overall survival was not reached in group 1 versus 65 months (51-not reached [NR]) in its matched group (p = 0.027); it was 96 months (49-NR) in group 2 versus 91 months (32-NR) in its matched group (p = 0.77). Median progression-free survival was 49 months (29-NR) in group 1 and was 25 months (range, 21-35 months) in its matched group (p = 0.0045); it was 31 months (22-NR) in group 2 and 28 months (range, 21-40 months) in its matched group (p = 0.0776). Tandem auto-RIC-allo-HSCT including new molecules and immunomodulation after transplantation could be used as a first-line treatment for high-risk myeloma patients., (Copyright © 2013 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)

Aim: To evaluate quantitatively and qualitatively the different CD34(+) cell subsets after priming by chemotherapy granulocyte colony-stimulating factor (± G-CSF) in patients with acute myeloid leukemia., Methods: Peripheral blood and bone marrow samples were harvested in 8 acute myeloid leukemia patients during and after induction chemotherapy. The CD34/CD38 cell profile was analyzed by multi-parameter flow cytometry. Adhesion profile was made using CXC chemokine receptor 4 (CXCR4) (CD184), VLA-4 (CD49d/CD29) and CD47., Results: Chemotherapy ± G-CSF mobilized immature cells (CD34(+)CD38(-) population), while the more mature cells (CD34(+)CD38(low) and CD34(+)CD38(+) populations) decreased progressively after treatment. Circulating CD34(+) cells tended to be more sensitive to chemotherapy after priming with G-CSF. CD34(+) cell mobilization was correlated with a gradual increase in CXCR4 and CD47 expression, suggesting a role in cell protection and the capacity of homing back to the marrow., Conclusion: Chemotherapy ± G-CSF mobilizes into the circulation CD34(+) bone marrow cells, of which, the immature CD34(+)CD38(-) cell population. Further manipulations of these interactions may be a means with which to control the trafficking of leukemia stem cells to improve patients' outcomes.

The BCR-ABL T315I mutation confers resistance to currently licensed tyrosine kinase inhibitors in chronic myelogenous leukemia. However, the impact of this mutation on survival in early stages of disease, in chronic phase, has never been detailed. Using matched pair analysis, a cohort of 64 patients with chronic phase chronic myelogenous leukemia harboring a T315I mutation and resistant to imatinib mesylate was compared to a similar cohort of 53 chronic phase patients resistant to imatinib, but with no detectable T315I mutation, in the pre-ponatinib era. These patients were matched according to age at diagnosis, interval between disease diagnosis and start of imatinib treatment, and duration of imatinib therapy. Kaplan-Meier survival analyses demonstrated the significant negative impact of the presence of the T315I mutation on overall survival (since imatinib-resistance: 48.4 months for T315I(+) patients versus not reached for T315I(-) ones; P=0.006) and failure-free survival (since imatinib-resistance: 34.7 months for T315I(+) patients versus not reached for T315I(-) patients; P=0.003). In addition, Cox proportional hazard models adjusted on overall survival demonstrated the negative influence of the T315I mutation (P=0.02, HR=2.54). These results confirm early assumptions concerning the poor prognosis of chronic phase chronic myelogenous leukemia patients with the T315I mutation who are not eligible for allogeneic transplantation, and demonstrate the need for more therapeutic options.

Background: Despite frequent anemia and multiple transfusions in patients undergoing chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia , recommendations for use of erythropoiesis-stimulating agents (ESAs) in these populations are still missing. The primary objective was the effect of ESA administration on patient's quality of life (QoL). Secondary objectives were hemoglobin (Hb) recovery, red blood cell (RBC) transfusions, overall survival, and event-free survival., Methods: Adult patients with Hb ≤ 11 g/dL after consolidation chemotherapy for acute myeloid leukemia (group 1), or after allo-HSCT for any hematological diseases (group 2), were prospectively included. ESA was administered subcutaneously once per week during a maximum period of 6 months and was stopped when Hb level reached 12 g/dL. A paired-matched analysis using a historical control group was performed for secondary endpoints. Fifty-two patients were included in group 1, and 55 patients were in group 2., Results: For the global population, a significant improvement of QoL was noticed with ESA use; 83% (group 1) and 71% (group 2) of patients achieved an Hb level ≥ 12 g/dL without transfusion requirement. The pair-matched analysis showed a reduction of 4 RBC units per patient in group 1 (P = .0002) and 3 RBC units per patient in group 2 (P = .04). No significant difference in terms of thromboembolic events, overall survival, and event-free survival was observed between ESA and control groups. A RBC transfusion median savings of €1712 per patient was estimated in each group., Conclusions: ESAs have a clinical and economic benefit on Hb recovery, could improve a patient's QoL, and lead to a significant reduction in number of RBC transfusions with no effect on survival., (Copyright © 2012 American Cancer Society.)

Anti-human leukocyte antigen (HLA) antibodies are associated with several complications in solid organ transplantations, but their impact after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not yet well defined. To evaluate the relevance of anti-HLA antibodies, we have retrospectively analyzed 107 peripheral blood allo-HSCTs after reduced-intensity conditioning regimen between 2005 and 2010. Acute myeloid leukemia and multiple myeloma were the most frequent malignancies in the cohort. The detection of anti-HLA antibodies was systematically performed in all patients before transplantation. Anti-HLA antibodies were present in 24 patients (22%). There was no significant impact of anti-HLA antibodies on engraftment, incidence of relapse, and incidence of acute graft-vs-host disease. The presence of anti-HLA antibodies was associated with significantly worse overall survival (p = 0.006) and event-free survival (p = 0.024) after stratification on sex. The 3-year probability of overall survival was 34% without anti-HLA antibodies and 16% in their presence. Patients with anti-HLA antibodies had a higher transplant-related mortality associated with life-threatening vascular complications. Our study supports that anti-HLA antibodies should be tested and considered as an important impacting factor for transplantation outcomes after reduced-intensity conditioning allo-HSCT. We recommend its consideration before allo-HSCT in the donor-recipient selection parameters., (Copyright © 2012. Published by Elsevier Inc.)

Construction works in healthcare establishments produce airborne fungal spores and considerably increase the risk of exposure of immunosuppressed patients. It is necessary to reinforce protective measures, or even to implement specific precautions, during this critical phase. The aim of these precautions is to protect both those areas, which are susceptible to dust, and patients at risk of a fungal infection particularly invasive aspergillosis. When construction works are planned in healthcare establishments, the first step consists in the characterisation of the environmental fungal risk and the second one in proposing risk management methods. It is then essential to establish impact indicators in order to evaluate the risk management precautions applied. The working group promoted by the French societies of medical mycology and hospital hygiene (SFMM & SF2H) details here both environmental and epidemiological impact indicators that can be used., (Copyright © 2012. Published by Elsevier SAS.)

T315I(+) Philadelphia chromosome-positive leukemias are inherently resistant to all licensed tyrosine kinase inhibitors, and therapeutic options remain limited. We report the outcome of allogeneic stem cell transplantation in 64 patients with documented BCR-ABL(T315I) mutations. Median follow-up was 52 months from mutation detection and 26 months from transplantation. At transplantation, 51.5% of patients with chronic myeloid leukemia were in the chronic phase and 4.5% were in advanced phases. Median overall survival after transplantation was 10.3 months (range 5.7 months to not reached [ie, still alive]) for those with chronic myeloid leukemia in the blast phase and 7.4 months (range 1.4 months to not reached [ie, still alive]) for those with Philadelphia chromosome-positive acute lymphoblastic leukemia but has not yet been reached for those in the chronic and accelerated phases of chronic myeloid leukemia. The occurrence of chronic GVHD had a positive impact on overall survival (P = .047). Transplant-related mortality rates were low. Multivariate analysis identified only blast phase at transplantation (hazard ratio 3.68, P = .0011) and unrelated stem cell donor (hazard ratio 2.98, P = .011) as unfavorable factors. We conclude that allogeneic stem cell transplantation represents a valuable therapeutic tool for eligible patients with BCR-ABL(T315I) mutation, a tool that may or may not be replaced by third-generation tyrosine kinase inhibitors.

Background: Pregnancy in women with paroxysmal nocturnal hemoglobinuria is rare, with few reports on maternal and fetal mortality rates., Design and Methods: A specific questionnaire designed to solicit data on pregnancies in women with paroxysmal nocturnal hemoglobinuria was sent to all members of the French Society of Hematology in January 2008., Results: We identified 27 pregnancies in 22 women at 10 French Society of Hematology centers between 1978 and 2008. The median age was 21.5 years at diagnosis of paroxysmal nocturnal hemoglobinuria and 27 years at pregnancy. None of these women had received eculizumab during their pregnancy. Maternal complications, consisting mostly of cytopenias requiring transfusions, occurred in 95% of cases. Two cases of severe aplastic anemia (de novo in one case and relapse in the other) were recorded. No thrombotic events occurred during pregnancy, whereas 4 postpartum thromboses (16%) were recorded, 2 of which were fatal (maternal mortality rate 8%). Most patients received antithrombotic prophylaxis during pregnancy and postpartum (n=16; 64%). Delivery was preterm in 29% of cases, and birth weight was less than 3 kg in 53% of cases. Fetal mortality rate was 4%., Conclusions: Pregnancy during paroxysmal nocturnal hemoglobinuria is associated with increased maternal and fetal mortality rates (8% and 4%, respectively, in this series). Maternal mortality is related to postpartum thromboses. Prophylactic anticoagulation is recommended during pregnancy and for six weeks postpartum.

Background: The treatment of older adults with acute myeloid leukemia (AML) is associated with unsatisfactory rates of response and overall survival. Identification of valuable factors that can facilitate therapeutic decision-making between intensive chemotherapy and investigational treatment strategies is warranted., Methods: Analysis of proliferative (white blood cell [WBC] count) and invasive (percentage of blast cells in peripheral blood) characteristics of leukemic blasts at diagnosis is presented in a population of 432 promyelocytic leukemia AML patients who are older than than 60 years and have been selected for entering onto five successive clinical trials combining an anthracycline and cytarabine., Results: Five groups of patients were defined according to these two relevant parameters used in clinical practice. Response rates were lower for the hyperproliferative groups (47% and 46%, respectively) and the nonproliferative groups displaying circulating blasts (56% and 59%, respectively) compared with those for the nonproliferative and noninvasive group (77%) (P = .0003). Median overall survivals were shorter for the hyperproliferative groups (5.7 and 5.8 months, respectively) compared with those observed for the nonproliferative groups (8.9 and12.6 months, respectively)., Conclusions: This combination of basic characteristics helps estimate the outcome of elderly AML patients who are usually selected for intensive chemotherapy. Although these factors remain valuable for identifying leukemia behavior, our study demonstrated that results of intensive chemotherapy in elderly patients remained poor, whatever the prognostic group. Comparison with recent data from the literature requires investigators to study results differently and to consider investigational therapy as being the most appropriate treatment even for this highly selected population., (Copyright © 2011. Published by Elsevier Inc.)

The treatment of chronic myeloid leukemia (CML) has considerably evolved since imatinib mesylate has been introduced as a new therapeutic weapon for this disease. The 5-year updated results of the IRIS study confirmed that imatinib mesylate is the best first line therapy for chronic phase CML with an overall survival of 90%. Responses improve with time and complete cytogenetic and major molecular levels reach 87 and 70% respectively at 5 years. However, despite these remarkable improvements, new problems arise as sub-optimal responses, imatinib-resistances with recently identified BCR-ABL protein point mutations, responsible for a variety of therapeutic consequences : imatinib dose increase, alternative treatments with second generation tyrosine kinase inhibitors (TKIs : dastinib, nilotinib) or allogeneic stem cell transplantation. The treatment of accelerated and blastic phases relies on imatinib +/- conventional chemotherapy, ideally followed by allogeneic stem cell transplantation, as newly developed TKIs are currently evaluated within this frame. Finally, BCR-ABL(T315I) mutations remain a new therapeutic critical challenge as none of the three TKIs (imatinib, nilotinib, dasatinib) can efficiently control such diseases.