Impact of central nervous system involvement in adult patients with Philadelphia-negative acute lymphoblastic leukemia: a GRAALL-2005 study.

Whereas the prognosis of adult patients with Philadelphia-negative acute lymphoblastic leukemia (ALL) has greatly improved since the advent of pediatric-inspired regimens, the impact of initial central nervous system (CNS) involvement has not been formerly re-evaluated. We report here the outcome of patients with initial CNS involvement included in the pediatric-inspired prospective randomized GRAALL-2005 study. Between 2006 and 2014, 784 adult patients (aged 18-59 years) with newly diagnosed Philadelphia-negative ALL were included, of whom 55 (7%) had CNS involvement. In CNSpositive patients, overall survival was shorter (median 1.9 years vs. not reached, HR=1.8 [1.3-2.6], P<0.001). While there was no statistical difference in cumulative incidence of relapse between CNS+ and CNS- patients (HR=1.5 [0.9-2.5], P=0.11), non-relapse mortality was significantly higher in those with initial CNS disease (HR=2.1 [1.2-3.5], P=0.01). This increase in toxicity was mostly observed in patients randomized to the high-dose cyclophosphamide arm and in those who received allogeneic stem cell transplantation. Exploratory landmark analyses did not show any association between either cranial irradiation or allogeneic stem cell transplantation and outcome. Despite improved outcome in young adult ALL patients with pediatric-inspired protocols, CNS involvement is associated with a worse outcome mainly due to excess toxicity, without improved outcome with allogeneic SCT.

Outcome of patients with newly diagnosed AML admitted to the ICU, including preemptive admission - a multi-center study.

Acute myeloid leukemia (AML) can lead to life-threatening complications that may require intensive care unit (ICU) management. It has been advocated that early preemptive (ePE) ICU admission, before the onset of organ failure, could benefit some high-risk patients such as those with hyperleukocytosis. The aim of this study was to retrospectively analyze the outcome of newly diagnosed AML patients who required ICU admission in five academic centers with a special focus on patients with an ePE admission strategy, i.e., those transferred to the ICU without any organ failure (modified SOFA score ≤ 2 [omitting thrombocytopenia] and no life-sustaining intervention in the first 24 h following ICU admission) before the start of induction therapy. Between January 2017 and December 2019, 428 patients were included among which 101 were admitted to the ICU. Among patients requiring life-sustaining interventions (n = 83), 18 (22%) died while in the ICU but ICU survivors had the same survival as those not admitted to the ICU. Patients with an ePE admission (n = 18) had more comorbidities and high-risk disease features such as hyperleukocytosis but required no life-sustaining interventions while in the ICU. In a subgroup analysis of patients with hyperleukocytosis ≥ 50 G/l at diagnosis (n = 85), patients not admitted to the ICU and those admitted with an ePE strategy had similar outcomes. This study provides encouraging results about ICU outcome in AML patients during induction therapy but the potential benefit of an ePE strategy must be confirmed prospectively.

Salvage haploidentical or cord-blood allogeneic stem cell transplantation after a prior alternative allograft in hematologic malignancies: A retrospective study from the SFGM-TC.

BACKGROUND: Haploidentical (haplo-) donors and cord-blood (CB) stem cells provide alternative transplant options in patients lacking an HLA-matched donor. In case of relapse or graft failure after a first alternative allogeneic hematopoietic stem cell transplant (HSCT), a second alternative HSCT (HSCT2) is rarely considered due to a high risk of toxicity. METHODS: A retrospective French multicentre study was performed, including patients with hematologic malignancies who underwent two consecutive HSCT from alternative donors. All data were exported from the national ProMISE database between 2000 and 2016. RESULTS: Forty-three patients (61.4%) received a CB-HSCT2 and 27 (38.6%) a haplo-HSCT2. Indications for HSCT were graft failure (51.4%) or disease progression (48.6%). Two-years probabilities of overall survival, progression-free survival and toxicity-related mortality were 18.5%, 17.8% and 55.8%, respectively. In multivariate analysis, complete remission status at HSCT2 and year of HSCT2 ≥ 2012 were significantly associated with a better outcome (with respectively hazard ratio [HR] = 0.42, p = .002 and HR = 0.5, p = .051). CONCLUSIONS: Neither the indication of HSCT2 nor the source of stem cell was more advantageous towards overall patient survival. A salvage haploidentical or cord-blood stem cell transplantation is a high-risk procedure, that may be considered for patients achieving a complete remission before receiving the second HSCT.

Safety and risk of febrile recurrence after early antibiotic discontinuation in high-risk neutropenic patients with haematological malignancies: a multicentre observational study.

BACKGROUND: Early antibiotic discontinuation according to the Fourth European Conference on Infections in Leukaemia (ECIL-4) recommendations is not systematically applied in high-risk neutropenic patients with haematological malignancies. METHODS: A retrospective multicentre observational study was conducted over 2 years to evaluate the safety of early antibiotic discontinuation for fever of unknown origin (FUO) during neutropenia after induction chemotherapy or HSCT, in comparison with a historical cohort. We used Cox proportional hazards models, censored on neutropenia resolution, to analyse factors associated with febrile recurrence. RESULTS: Among 147 included patients in the ECIL-4 cohort, mainly diagnosed with acute leukaemia (n = 104, 71%), antibiotics were discontinued during 170 post-chemotherapy neutropenic episodes. In comparison with the historical cohort of 178 episodes of neutropenia without antibiotic discontinuation, no significant differences were observed regarding febrile recurrences [71.2% (121/170) versus 71.3% (127/178), P = 0.97], admission in ICUs [6.5% (11/170) versus 11.2% (20/178), P = 0.17], septic shock [0.6% (1/170) versus 3.9% (7/178), P = 0.07] and 30 day mortality [1.4% (2/147) versus 2.7% (4/150), P = 0.084]. In the ECIL-4 cohort, the rate of bacteraemia in case of febrile recurrence was higher [27.1% (46/170) versus 11.8% (21/178), P < 0.01] and antibiotic consumption was significantly lower (15.5 versus 19.9 days, P < 0.001). After early antibiotic discontinuation according to ECIL-4 recommendations, enterocolitis was associated with febrile recurrence [HR = 2.31 (95% CI = 1.4-3.8), P < 0.001] and stage III-IV oral mucositis with bacteraemia [HR = 2.26 (95% CI = 1.22-4.2), P = 0.01]. CONCLUSIONS: After an FUO episode in high-risk neutropenia, compliance with ECIL-4 recommendations for early antibiotic discontinuation appears to be safe and mucosal damage was associated with febrile recurrence and bacteraemia. Prospective interventional studies are warranted to assess this strategy in high-risk neutropenic patients.

Outcomes after allogeneic hematopoietic stem cell transplantation for adults with primary mediastinal B cell lymphoma: a SFGM-TC and LYSA study.

Background: Despite therapeutic progress, 10 to 30% of adult patients with primary mediastinal B cell lymphoma (PMBCL) are primary refractory or experience early relapse (R/R). Allogeneic stem cell transplantation (allo-HSCT) thus remains a potentially curative option in this setting.Material and Methods: In this multicenter retrospective study, the outcomes of 33 French and Belgian adult patients allo-transplanted for R/R PMBCL between January 1999 and December 2018, were examined.Results: At allo-HSCT time, patients had received a median of 3 treatment lines, 50% of them were in complete response, 40% in partial response and 10% had a progressive disease. Forty-two percent of the donors were siblings and 39% matched related. The median follow-up for alive patients was 78 months (3.5-157). Considering the whole cohort, 2-year overall survival (OS), progression free survival (PFS) and graft-versus-host disease-free/relapse-free survival (GRFS) were 48% (95%CI: 33-70), 47% (95%CI: 33-68) and 38.5% (95%CI: 25-60) respectively. Cumulative incidence of relapse and non-relapse mortality rates were respectively 34% (95%CI: 18-50) and 18% (95%CI: 7-34). Disease status at transplant was the only factor predicting survivals, patients with progressive disease showing significant lower 2-year PFS (HR: 6.12, 95%CI: 1.32-28.31, p = 0.02) and OS (HR: 7.04, 95%CI: 1.52-32.75, p = 0.013). A plateau was observed for OS and PFS after 4 years with 10 patients alive after this date, suggesting that almost one third of the patients effectively salvaged and undergoing allo-SCT could be cured.Conclusion: This study indicates that allo-HSCT is a valid therapeutic option for R/R PMBCL, providing durable remissions.

Efficacy of minimal residual disease driven immune-intervention after allogeneic hematopoietic stem cell transplantation for high-risk chronic lymphocytic leukemia: results of a prospective multicenter trial.

Allogeneic hematopoietic stem cell transplantation (HSCT) remains a potentially curative and useful strategy in high-risk relapsing CLL. Minimal Residual Disease (MRD) assessment at 12 months post-HSCT is predictive of relapse. This phase 2 study aimed to achieve M12 MRD negativity (MRDneg) using MRD-driven immune-intervention (Md-PII) algorithm based on serial flow-cytometry blood MRD, involving cyclosporine tapering followed if failure by donor lymphocytes infusions. Patients had high-risk CLL according to 2006 EBMT consensus, in complete or partial response with lymphadenopathy < 5 cm and comorbidity score ≤ 2. Donors were HLA-matched sibling or matched unrelated (10/10). Forty-two enrolled patients with either 17p deletion (front-line, n=11; relapse n=16) or other high-risk relapse (n=15) received reduced intensity-conditioning regimen before HSCT and were submitted to Md-PII. M12-MRDneg status was achieved in 64% versus 14.2% before HSCT. With a median follow-up of 36 months (range, 19-53), 3-year overall survival, non-relapse mortality and cumulative incidence of relapse are 86.9% (95%CI, 70.8-94.4), 9.5% (95%CI, 3.7-23.4) and 29.6% (95%CI, 17.3-47.7). Incidence of 2-year limited and extensive chronic graft versus host disease (cGVHD) is 38% (95%CI, 23-53) and 23% (95%CI, 10-36) including 2 cases post Md-PII. Fifteen patients converted to MRDneg either after CsA withdrawal (n=12) or after cGVHD (n=3). As a time-dependent variable, MRDneg achievement at any time-point correlates with reduced relapse (HR=0.14 [0.04-0.53], p=0.004) and improvement of both progression free (HR=0.18 [0.06-0.6], p<0.005) and overall (HR: 0.18 [0.03-0.98], p=0.047) survival. These data highlight the value of MRD-driven immune-intervention to induce prompt MRD clearance in the therapy of CLL.

Molecular classification and prognosis in younger adults with acute myeloid leukemia and intermediate-risk cytogenetics treated or not by gemtuzumab ozogamycin: Final results of the GOELAMS/FILO acute myeloid leukemia 2006-intermediate-risk trial.

In this randomized phase 3 study, the FILO group tested whether the addition of 6 mg/m2 of gemtuzumab ozogamycin (GO) to standard chemotherapy could improve outcome of younger patients with de novo acute myeloid leukemia (AML) and intermediate-risk cytogenetics. GO arm was prematurely closed after 254 inclusions because of toxicity. A similar complete remission rate was observed in both arms. Neither event-free survival nor overall survival were improved by GO in younger AML patients (<60 years) ineligible for allogeneic stem-cell transplantation. (P = .086; P = .149, respectively). Using unsupervised hierarchical clustering based on mutational analysis of seven genes (NPM1, FLT3-ITD, CEBPA, DNMT3A, IDH1, IDH2, and ASXL1), six clusters of patients with significant different outcome were identified. Five clusters were based on FLT3-ITD, NPM1, and CEBPA mutations as well as epigenetic modifiers (DNMT3A, IDH1/2, ASXL1), whereas the last cluster, representing 25% of patients, had no mutation and intermediate risk. One cluster isolated FLT3-ITD mutations with higher allelic ratio and a very poor outcome. The addition of GO had no impact in these molecular clusters. Although not conclusive for GO impact in AML patients <60 years, this study provides a molecular classification that distinguishes six AML clusters influencing prognosis in younger AML patients with intermediate-risk cytogenetic.

Prognostic value of interim FDG PET-CT in patients older than 60 years with diffuse large B-cell lymphoma treated by PMitCEBO plus rituximab. Comparison between Deauville 5-point scale and International Harmonization Project criteria.

BACKGROUND: Advanced age is an independent poor prognostic factor of diffuse large B-cell lymphoma (DLBCL). PMitCEBO (mitoxantrone, cyclophosphamide, etoposide, vincristine, bleomycin, and prednisolone) is an alternative to the cyclophosphamide, doxorubicin, vincristine, and prednisolone regimen to decrease side effects in elderly patients. Many studies have shown prognostic value of an interim FDG PET-CT to predict survival. A recent consensus (ICML, Lugano 2013) has suggested using the 5-point scale Deauville criteria instead of those of the International Harmonization Project (IHP) to visually assess the response on interim PET. The objective of this study was to evaluate the prognostic value of an interim FDG PET-CT in patients older than 60 with treated DLBCL and to compare IHP and 5-PS Deauville visual interpretation to predict survival. METHODS: Forty-eight patients (mean age 73.2±5.2 years) treated by R-PMitCEBO for DLBCL undergoing FDG PET-CT before and after 3 cycles of treatment were retrospectively included. Event-free survival and overall survival were determined by Kaplan-Meier method and compared with interim PET-CT results using IHP and 5-PS Deauville criteria. RESULTS: Interim PET results using 5-PS Deauville criteria were significantly correlated with EFS (P<0.0001) and OS (P=0.001) whereas they were moderately correlated with EFS (P=0.046) and not with OS (P=0.106) using IHP criteria. Two-year EFS and OS rates were 86.5% and 89.2%, respectively, for patients in 1-3 score group, and 27.3% and 36.4%, respectively, for patients in ≥4 score group using the Deauville criteria. CONCLUSIONS: Our results confirmed the prognostic value of an interim PET-CT in elderly patients with DLBCL and the better performance of the 5-PS Deauville criteria.

Allogeneic Stem Cell Transplantation in Therapy-Related Myelodysplasia after Autologous Transplantation for Lymphoma: A Retrospective Study of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy.

Therapy-related myelodysplastic syndrome (t-MDS) after autologous stem cell transplantation (ASCT) is a rare complication with no curative option. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be considered for eligible patients and has been understudied in t-MDS. We report 47 consecutive patients with t-MDS after an ASCT who underwent allo-HSCT with a median age of 58 years (range, 30 to 71 years) at transplantation and a median follow-up of 22 months (range, 0.7 to 107). The median overall survival (OS) was 6.9 months (95% confidence interval [CI], 0 to 19 months). OS rates were 45% (29% to 60%) and 30% (15% to 45%) at 1 and 3 years after transplantation, respectively. On univariate analysis, prior therapy for t-MDS before allo-HSCT (P = .02) and mismatched donors (P = .004) were associated with poor OS. Three-year nonrelapse mortality (NRM) and relapse rates were 44% (25% to 63%) and 41% (22% to 61%), respectively. Mismatched donors (P < .001) were associated with higher NRM and a high-risk MDS (P = .008) with a higher relapse risk. On multivariate analysis, HLA mismatch was associated with higher NRM (hazard ratio, 6.21; 95% CI, 1.63 to 23.62; P = .007). In conclusion, our results suggest that one third of the patients who develop t-MDS after an ASCT for lymphoma are cured after an allo-HSCT. The use of mismatched donors with standard graft-versus-host disease prophylaxis should be avoided in such an indication for allo-HSCT. It will be worthwhile to see if the implementation of cyclophosphamide post-transplantation will improve the outcome with mismatched donors.

Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study.

STOP second generation (2G)-tyrosine kinase inhibitor (TKI) is a multicenter observational study designed to evaluate 2G-TKI discontinuation in chronic myeloid leukemia (CML). Patients receiving first-line or subsequent dasatinib or nilotinib who stopped therapy after at least 3 years of TKI treatment and in molecular response 4.5 (MR4.5) with undetectable BCR-ABL1 transcripts for the 2 preceding years at least were eligible for inclusion. This interim analysis reports outcomes of 60 patients with a minimum follow-up of 12 months (median 47, range: 12-65). Twenty-six patients (43.3%) experienced a molecular relapse defined as the loss of a major molecular response (MMR). Relapses occurred after a median time of 4 months (range: 1-38). Cumulative incidences of molecular relapse by 12 and 48 months were 35% (95% confidence interval [CI], 24.79% to 49.41%) and 44.76% (95% CI, 33.35% to 59.91%), respectively. Treatment-free remission (TFR) rates at 12 and 48 months were 63.33% (95% CI, 51.14% to 75.53%) and 53.57% (95% CI, 40.49% to 66.65%), respectively. In univariate analysis, prior suboptimal response or TKI resistance was the only baseline factor associated with significantly worse outcome. A landmark analysis demonstrated that loss of MR4.5 3 months after stopping TKI was predictive of failure to maintain MMR later on. During the treatment-free phase, no progression toward advanced phase CML occurred, and all relapsing patients regained MMR and MR4.5 after restarting therapy. In conclusion, discontinuation of first-line or subsequent 2G-TKI yields promising TFR rates without safety concerns. Further research is encouraged to better define conditions that will offer patients the highest chance to remain free from 2G-TKI therapy.

DNMT3A mutation is associated with increased age and adverse outcome in adult T-cell acute lymphoblastic leukemia.

The prognostic implications of DNMT3A genotype in T-cell acute lymphoblastic leukemia are incompletely understood. We performed comprehensive genetic and clinico-biological analyses of T-cell acute lymphoblastic leukemia patients with DNMT3A mutations treated during the GRAALL-2003 and -2005 studies. Eighteen of 198 cases (9.1%) had DNMT3A alterations. Two patients also had DNMT3A mutations in non-leukemic cell DNA, providing the first potential evidence of age-related clonal hematopoiesis in T-cell acute lymphoblastic leukemia. DNMT3A mutation was associated with older age (median 43.9 years vs 29.4 years, P<0.001), immature T-cell receptor genotype (53.3% vs 24.4%, P=0.016) and lower remission rates (72.2% mutated vs 94.4% non-mutated, P=0.006). DNMT3A alterations were significantly associated with worse clinical outcome, with higher cumulative incidence of relapse (HR 2.33, 95% CI: 1.05-5.16, P=0.037) and markedly poorer event-free survival (HR 3.22, 95% CI: 1.81-5.72, P<0.001) and overall survival (HR 2.91, 95% CI: 1.56-5.43, P=0.001). Adjusting for age as a covariate, or restricting the analysis to patients over 40 years, who account for almost 90% of DNMT3A-mutated cases, did not modify these observations. In multivariate analysis using the risk factors that were used to stratify treatment during the GRAALL studies, DNMT3A mutation was significantly associated with shorter event-free survival (HR 2.33, 95% CI: 1.06 - 4.04, P=0.02). Altogether, these results identify DNMT3A genotype as a predictor of aggressive T-cell acute lymphoblastic leukemia biology. The GRAALL-2003 and -2005 studies were registered at http://www.ClinicalTrials.gov as #NCT00222027 and #NCT00327678, respectively.

Nationwide survey on the use of eltrombopag in patients with severe aplastic anemia: a report on behalf of the French Reference Center for Aplastic Anemia.

Few therapeutic options are available for patients with aplastic anemia who are ineligible for transplantation or refractory to immunosuppressive therapy. Eltrombopag was recently shown to produce trilineage responses in refractory patients. However, the effects of real-life use of this drug remain unknown. This retrospective study (2012-2016) was conducted by the French Reference Center for Aplastic Anemia on patients with relapsed/refractory aplastic anemia, and patients ineligible for antithymocyte globulin or transplantation, who received eltrombopag for at least 2 months. Forty-six patients with aplastic anemia were given eltrombopag without prior antithymocyte globulin treatment (n=11) or after antithymocyte globulin administration (n=35) in a relapsed/refractory setting. Eltrombopag (median daily dose 150 mg) was introduced 17 months (range, 8-50) after the diagnosis of aplastic anemia. At last followup, 49% were still receiving treatment, 9% had stopped due to a robust response, 2% due to toxicity and 40% due to eltrombopag failure. Before eltrombopag treatment, all patients received regular transfusions. The overall rates of red blood cell and platelet transfusion independence were 7%, 33%, 46% and 46% at 1, 3, 6 months and last follow-up. Responses were slower to develop in antithymocyte treatment-naïve patients. In patients achieving transfusion independence, hemoglobin concentration and platelet counts improved by 3 g/dL (interquartile range, 1.4-4.5) and 42×109/L (interquartile range, 11-100), respectively. Response in at least one lineage (according to National Institutes of Health criteria) was observed in 64% of antithymocyte treatment-naïve and 74% of relapsed/refractory patients, while trilineage improvement was observed in 27% and 34%, respectively. We found high rates of hematologic improvement and transfusion independence in refractory aplastic anemia patients but also in patients ineligible for antithymocyte globulin receiving first-line treatment. In conclusion, elderly patients unfit for antithymocyte globulin therapy may benefit from eltrombopag.

Non-adherence to treatment with cytoreductive and/or antithrombotic drugs is frequent and associated with an increased risk of complications in patients with polycythemia vera or essential thrombocythemia (OUEST study).

The purpose of this study was to identify the incidence, causes and impact of non-adherence to oral and subcutaneous chronic treatments for patients with polycythemia vera or essential thrombocythemia. Patients receiving cytoreductive drugs for polycythemia vera or essential thrombocythemia were recruited at our institution (Observatoire Brestois des Néoplasies Myéloprolifératives registry). They completed a one-shot questionnaire designed by investigators (Etude de l'Observance Thérapeutique et des Effets Secondaires des Traitements study). Data about complications (thrombosis, transformation and death) at any time in the patient's life (before diagnosis, up until consultation and after the completion of the questionnaire) were collected. Sixty-five (22.7%) of 286 patients reported poor adherence (<90%) to their treatment with cytoreductive drugs and 46/255/18%) also declared non-adherence to antithrombotic drugs. In total, 85/286 patients (29.7%) declared they did not adhere to their treatment. Missing an intake was rare and was mostly due to forgetfulness especially during occupational travel and holidays. Patients who did not adhere to their treatment were characterized by younger age, living alone, having few medications but a high numbers of pills and determining their own schedule of drug intake. Having experienced thrombosis or hematologic evolution did not influence the adherence rate. Non-adherence to oral therapy was associated with a higher risk of phenotypic evolution (7.3 versus 1.8%, P=0.05). For patients treated for polycythemia vera or essential thrombocythemia, non-adherence to cytoreductive and/or antithrombotic therapies is frequent and is influenced by age, habitus and concomitant treatments, but not by disease history or treatment side effects. Phenotypic evolution seems to be more frequent in the non-adherent group.

Incidence and impact of atrial arrhythmias on thrombotic events in MPNs.

Atrial arrhythmias (AA) induce a high rate of thromboses and require vitamin K antagonists (VKA) or direct anticoagulants (DOAC) prescriptions. Essential thrombocythemia (ET) and polycythemia vera (PV) are also pro-thrombotic diseases. The prevention of thromboses is based on the association of cytoreductive drug and low-dose aspirin (LDA). We studied the incidence and complications of AA among patients with ET or PV. We identified 96/713 patients (13.5%) carrying AA. These patients were older (median 72.1 vs. 61.3 years old, p < 0.0001). In a case-control analysis, we observed that patients with AA had a higher frequency of cardiovascular risk factors (77/96, 80% vs. 61/96, 61%; p = 0.01). A higher incidence of thromboses before and after myeloproliferative neoplasm (MPN) diagnosis was seen in this group: 26/96, 27.1% vs. 14/96, 14.6% (p = 0.03) and 34/96, 35% vs. 18/96, 18.8% (p = 0.009). Most of the events were arterial (82 vs. 61%, p = 0.09). This translates into a shorter thrombosis-free survival (11.0 vs. 21.6 years, p = 0.01). Continuation of LDA in this situation exposed patients to more thrombotic events (p = 0.04) but VKA did not seem to be good anticoagulant drugs either. The association of AA and MPN is more frequent than expected. AA clearly increased the thrombotic risk of these patients. Anticoagulant drugs should be carefully managed between cardiologists and hematologists. Association of LDA and VKA or the role of DOAC in such population should be rapidly discussed to reduce the thrombotic rate.

Similar outcome of allogeneic stem cell transplantation after myeloablative and sequential conditioning regimen in patients with refractory or relapsed acute myeloid leukemia: A study from the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire.

Patients with acute myeloid leukemia (AML) in relapse or refractory to induction therapy have a dismal prognosis. Allogeneic hematopoietic stem cell transplantation is the only curative option. In these patients, we aimed to compare the results of a myeloablative transplant versus a sequential approach consisting in a cytoreductive chemotherapy followed by a reduced intensity conditioning regimen and prophylactic donor lymphocytes infusions. We retrospectively analyzed 99 patients aged 18-50 years, transplanted for a refractory (52%) or a relapsed AML not in remission (48%). Fifty-eight patients received a sequential approach and 41 patients a myeloablative conditioning regimen. Only 6 patients received prophylactic donor lymphocytes infusions. With a median follow-up of 48 months, 2-year overall survival was 39%, 95% confidence interval (CI) (24-53) in the myeloablative group versus 33%, 95% CI (21-45) in the sequential groups (P = .39), and 2-year cumulative incidence of relapse (CIR) was 57% versus 50% respectively (P = .99). Nonrelapse mortality was not higher in the myeloablative group (17% versus 15%, P = .44). In multivariate analysis, overall survival, CIR and nonrelapse mortality remained similar between the two groups. However, in multivariate analysis, sequential conditioning led to fewer acute grade II-IV graft versus host disease (GVHD) (HR for sequential approach = 0.37; 95% CI: 0.21-0.65; P < .001) without a significant impact on chronic GVHD (all grades and extensive). In young patients with refractory or relapsed AML, myeloablative transplant and sequential approach offer similar outcomes except for a lower incidence of acute GvHD after a sequential transplant.

Acute myeloid leukaemia (FAB AML-M4Eo) with cryptic insertion of cbfb resulting in cbfb-Myh11 fusion.

Inv(16)(p13q22) and t(16;16)(p13;q22) are cytogenetic hallmarks of acute myelomonoblastic leukaemia, most of them associated with abnormal bone marrow eosinophils [acute myeloid leukaemia French-American-British classification M4 with eosinophilia (FAB AML-M4Eo)] and a relatively favourable clinical course. They generate a 5'CBFB-3'MYH11 fusion gene. However, in a few cases, although RT-PCR identified a CBFB-MYH11 transcript, normal karyotype and/or fluorescent in situ hybridization (FISH) analyses using commercially available probes are found. We identified a 32-year-old woman with AML-M4Eo and normal karyotype and FISH results. Using two libraries of Bacterial Artificial Chromosome clones on 16p13 and 16q22, FISH analyses identified an insertion of 16q22 material in band 16p13, generating a CBFB-MYH11 type A transcript. Although very rare, insertions should be searched for in patients with discordant cytological and cytogenetic features because of the therapeutic consequences. Copyright © 2015 John Wiley & Sons, Ltd.

Impact of body-surface area on patients' outcome in younger adults with acute myeloid leukemia.

OBJECTIVES: Anthracyclines and cytarabine are cornerstones for intensive chemotherapy in acute myeloid leukemia (AML). The goals of this study were to comprehensively assess deviations from theoretical doses and the impact of body-surface area (BSA) on patients' characteristics, physicians' strategy, dose adjustment, and clinical outcome. METHODS: The GOELAMS 2001 phase III trial included 823 AML patients below 60 years of age. In the course of treatment, anthropomorphic parameters and chemotherapy doses were prospectively registered. RESULTS: Very high BSA (≥2.15 m2 ) was the factor most significantly associated with the physician's decision to reduce chemotherapy doses during induction and postremission therapy. Despite similar AML characteristics and therapeutic strategies, the very high BSA group exhibited a significantly worse survival (5-years OS of 27%) compared to the low (BSA≤1.5 m2 ), intermediate (1.5 m2

Keep in Mind Quality of Life: Outcome of a Ten-Year Series of Post-Transplantation Early Relapses in Childhood Acute Lymphoblastic Leukemia-A Report from the Grand Ouest Oncology Study Group for Children in France.

Relapses of acute lymphoblastic leukemia (ALL) early after hematopoietic stem cell transplantations in children are uncommon but associated with a very poor prognosis. Whereas there are no current recommendations for the management of these relapses, the children's quality of life is an important issue. We studied the outcomes, including 1-year overall survival, complete remission, and quality of life, of 19 children with ALL who relapsed within the first year after their transplantation treated in the 5 participating centers between 2000 and 2011 Patients were distributed as follows: supportive care only (group A), outpatient treatment (mainly steroid and vincristine, group B), or intensive inpatient treatment (group C). There were no significant differences in 1-year overall survival (31.5% for the entire cohort) or remission rate for time between transplantation and relapse (< 6 months or 6 to 12 months), transplantation or disease characteristics, or treatment group. However, time spent in hospital (for treatment and complications) significantly differed between treatment groups B and C (20.8% ± 13.0 versus 59.1% ± 32.9, respectively; P < .05). No differences in organ toxicities, school attendance, or Lansky scores were found between treatment groups. Our sample size-limited data indicate, in a prepersonalized medicine era, that children treated with steroid and vincristine have the same prognosis as those treated with intensive therapy, but they may benefit from improved quality of life. Nevertheless, new therapeutic strategies are required and future prospective trials would help to establish recommendations.

Management of Myelodysplastic Syndrome Relapsing after Allogeneic Hematopoietic Stem Cell Transplantation: A Study by the French Society of Bone Marrow Transplantation and Cell Therapies.

To find out prognostic factors and to investigate different therapeutic approaches, we report on 147 consecutive patients who relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS). Sixty-two patients underwent immunotherapy (IT group, second allo-HSCT or donor lymphocyte infusion), 39 received cytoreductive treatment alone (CRT group) and 46 were managed with palliative/supportive cares (PSC group). Two-year rates of overall survival (OS) were 32%, 6%, and 2% in the IT, CRT, and PSC groups, respectively (P < .001). In multivariate analysis, 4 factors adversely influenced 2-year rates of OS: history of acute graft-versus-host disease (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.26 to 2.67; P = .002), relapse within 6 months (HR, 2.69; 95% CI, .82 to 3.98; P < .001), progression to acute myeloid leukemia (HR, 2.59; 95% CI, 1.75 to 3.83; P < .001), and platelet count < 50 G/L at relapse (HR, 1.68; 95% CI, 1.15 to 2.44; P = .007). A prognostic score based on those factors discriminated 2 risk groups with median OSs of 13.2 versus 2.4 months, respectively (P < .001). When propensity score, prognostic score, and treatment strategy were included in Cox model, immunotherapy was found to be an independent factor that favorably impacts OS (HR, .40; 95% CI, .26 to .63; P < .001). In conclusion, immunotherapy should be considered when possible for MDS patients relapsing after allo-HSCT.

Allogeneic hematopoietic stem cell transplantation for T-prolymphocytic leukemia: a report from the French society for stem cell transplantation (SFGM-TC).

T-prolymphocytic leukemia (T-PLL), a rare aggressive mature T-cell disorder, remains frequently resistant to conventional chemotherapy. Studies have suggested that allogeneic hematopoietic stem cell transplantation (HSCT) might possibly serve to consolidate the response to initial chemotherapy. The current report summarizes the outcome of 27 T-PLL cases identified in the registry in French Society for stem cell transplantation (SFGM-TC). Prior to HSCT, 14 patients were in complete remission (CR), 10 in partial response, three refractory, or in progression. Following HSCT, 21 patients achieved CR as best response. With a median follow-up for surviving patients of 33 (range, 6-103) months, 10 patients are still alive in continuous CR. Overall survival and progression-free survival estimates at 3 yr were 36% (95% CI: 17-54%) and 26% (95% CI: 14-45%), respectively. The relapse incidence after HSCT was 47% occurring at a median of 11.7 (range, 2-24) months. Overall cumulative incidence of transplant-related mortality was 31% at 3 yr. These results suggest that HSCT may allow long-term survival in patients with T-PLL following induction treatment; however, it is associated with a significant rate of toxicity.