Outcome after allogeneic stem cell transplantation with haploidentical versus HLA-matched donors in patients with higher-risk MDS.

peer reviewedAllogeneic hematopoietic stem cell transplantation remains the best curative option for higher-risk myelodysplastic syndrome. The presence of monosomal karyotype and/or complex karyotype abnormalities predicts inferior survival after allo-SCT in MDS patients. Haploidentical allo-SCT has been increasingly used in acute leukemia (AL) and has similar results as using HLA-matched donors, but data on higher-risk MDS is sparse. We compared outcomes in 266 patients with higher-risk MDS after HLA-matched sibling donor (MSD, n = 79), HLA-matched unrelated donor (MUD, n = 139) and HLA haploidentical donor (HID, n = 48) from 2010 to 2019. Median donor age differed between the three groups (p < 0.001). The overall survival was significantly different between the three groups with a better OS observed in the MUD group (p = 0.014). This observation could be explained by a higher progression-free survival with MUD (p = 0.014). The cumulative incidence of grade 2-4 acute GvHD was significantly higher in the HID group (p = 0.051). However, in multivariable analysis, patients transplanted using an HID had comparable mortality to patients transplanted using a MUD (subdistribution hazard ratio [sHR]: 0.58 [0.32-1.07]; p = 0.080) and a MSD ([sHR]: 0.56 [0.28-1.11]; p = 0.094). MUD do not remain a significant positive predictor of survival, suggesting that beyond the donor-recipient HLA matching, the donor age might impact recipient outcome

Bone marrow graft versus peripheral blood graft in haploidentical hematopoietic stem cells transplantation: a retrospective analysis in1344 patients of SFGM-TC registry.

peer reviewedThe use of peripheral blood (PB) or bone marrow (BM) stem cells graft in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis remains controversial. Moreover, the value of adding anti-thymoglobulin (ATG) to PTCy is unknown. A total of 1344 adult patients received an unmanipulated haploidentical transplant at 37 centers from 2012 to 2019 for hematologic malignancy. We compared the outcomes of patients according to the type of graft, using a propensity score analysis. In total population, grade II-IV and III-IV acute GVHD (aGVHD) were lower with BM than with PB. Grade III-IV aGVHD was lower with BM than with PB + ATG. All outcomes were similar in PB and PB + ATG groups. Then, in total population, adding ATG does not benefit the procedure. In acute leukemia, myelodysplastic syndrome and myeloproliferative syndrome (AL-MDS-MPS) subgroup receiving non-myeloablative conditioning, risk of relapse was twice greater with BM than with PB (51 vs. 22%, respectively). Conversely, risk of aGVHD was greater with PB (38% for aGVHD II-IV; 16% for aGVHD III-IV) than with BM (28% for aGVHD II-IV; 8% for aGVHD III-IV). In this subgroup with intensified conditioning regimen, risk of relapse became similar with PB and BM but risk of aGVHD III-IV remained higher with PB than with BM graft (HR = 2.0; range [1.17-3.43], p = 0.012)

Administration of direct oral anticoagulants in patients with myeloproliferative neoplasms

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Biosimilars of filgrastim in autologous stem cell transplantation: certain differences for myeloma patients only.

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Pneumocystis jirovecii haplotypes at the internal transcribed spacers of the rRNA operon in French HIV-negative patients with diverse clinical presentations of Pneumocystis infections.

International audiencePneumocystis jirovecii, a transmissible fungus, is the causative agent of pulmonary infections. Its genomic diversity has appeared in reports from around the world but data on P. jirovecii genotypes in France are still limited. This study describes the typing of P. jirovecii isolates from 81 HIV-negative patients monitored at Brest University Hospital, Brittany, France, 40 of whom developed Pneumocystis pneumonia (PcP), and remaining 41 patients were colonized by the fungus. The isolates were assayed at the internal transcribed spacer (ITS)1 and ITS2 under improved amplification conditions to avoid in vitro ITS recombination. P. jirovecii ITS haplotypes were identified in 56/81 patients (31 PcP patients and 25 patients who were colonized) which revealed a high diversity in that 27 different haplotypes were identified. Eg was the most frequent haplotype (31/56, 55.3%), followed by Ec and Ai (5/56, 8.9% each). In contrast, Ne, usually the second most frequent haplotype in Europe and the USA, was observed in only 2/56 patients (3.6%). Mixed infections were detected in 18/56 patients (32.1%; 12 PcP patients and six who were colonized). No significant differences were observed in haplotype diversity, frequency of peculiar haplotypes, and mixed infection occurrence, between the two patient populations. The study, conducted with the largest HIV-negative patient population investigated so far, shows that ITS typing remains an efficient method for characterizing P. jirovecii among human populations, whatever their clinical presentation of Pneumocystis infections

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

International audienceBackground 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 &lt; 0.01] and antibiotic consumption was significantly lower (15.5 versus 19.9 days, P &lt; 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 &lt; 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

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)

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High CD3+ and CD34+ peripheral blood stem cell grafts content is associated with increased risk of graft-versus-host disease without beneficial effect on disease control after reduced-intensity conditioning allogeneic transplantation from matched unrelated donors for acute myeloid leukemia - an analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Inconsistent results have been reported regarding the influence of graft composition on the incidence of graft versus host disease (GVHD), disease control and survival after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplantation (allo-PBSCT). These discrepancies may be at least in part explained by the differences in disease categories, disease status at transplant, donor type and conditioning. The current retrospective EBMT registry study aimed to analyze the impact of CD3+ and CD34+ cells dose on the outcome of RIC allo-PBSCT in patients with acute myelogenous leukemia (AML) in first complete remission, allografted from HLA-matched unrelated donors (10 of 10 match). We included 203 adults. In univariate analysis, patients transplanted with the highest CD3+ and CD34+ doses (above the third quartile cut-off point values, >347 x 10^6/kg and >8.25 x 10^6 /kg, respectively) had an increased incidence of grade III-IV acute (a) GVHD (20% vs. 6%, P = .003 and 18% vs. 7%, P = .02, respectively). There was no association between cellular composition of grafts and transplant-related mortality, AML relapse, incidence of chronic GVHD and survival. Neither engraftment itself nor the kinetics of engraftment were affected by the cell dose. In multivariate analysis, CD3+ and CD34+ doses were the only adverse predicting factors for grade III-IV aGVHD (HR = 3.6; 95%CI: 1.45-9.96, P = .006 and 2.65 (1.07-6.57), P = .04, respectively). These results suggest that careful assessing the CD3+ and CD34+ graft content and tailoring the cell dose infused may help in reducing severe acute GVHD risk without negative impact on the other transplantation outcomes

In-depth time-dependent analysis of the benefit of allo-HSCT for elderly patients with CR1 AML: a FILO study

The benefit of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute myeloid leukemia (AML) aged > 60 years remains a matter of debate, notably when performed in first complete remission (CR1). To clarify this issue, the French Innovative Leukemia Organization (FILO) performed a 10-year real-world time-dependent analysis. The study enrolled patients between 60 and 70 years of age with AML in CR1 after intensive chemotherapy with intermediate (IR) or unfavorable (UR) risk according to the European LeukemiaNet (ELN) 2010 classification. The impact of allo-HSCT was analyzed through three models: (1) time-dependent Cox; (2) multistate for dynamic prediction; and (3) super landmark. The study enrolled 369 (73%) IR and 138 (27%) UR patients with AML, 203 of whom received an allo-HSCT. Classical multivariate analysis showed that allo-HSCT significantly improved relapse-free survival (RFS; hazard ratio [HR] [95% confidence interval (CI)], 0.47 [0.35-0.62]; P < .001) and overall survival (OS; HR [95% CI], 0.56 [0.42-0.76]; P < .001), independently of the ELN risk group. With the multistate model, the predicted 5-year probability for IR and UR patients to remain in CR1 without allo-HSCT was 8% and 1%, respectively. Dynamic predictions confirmed that patients without allo-HSCT continue to relapse over time. Finally, the super landmark model showed that allo-HSCT significantly improved RFS (HR [95% CI], 0.47 [0.36-0.62]; P < .001) and OS (HR [95% CI], 0.54 [0.40-0.72]; P < .001). allo-HSCT in CR1 is reported here as significantly improving the outcome of fit older patients with AML. Long-term RFS without allo-HSCT is very low (< 10%), supporting allo-HSCT as being the best curative option for these patients