Three reports address the protection of the vulnerable population of patients with hematologic malignancies in the face of the ongoing COVID pandemic. The reports suggest that some patients who fail ...to mount a B-cell response to vaccine may nevertheless have protective T cell responses. As a group, these reports suggest that patients should continue to be immunized with additional doses to attempt to improve immune response but that they need to maintain the precautions recommended for the unvaccinated.
Karyotypic analysis at time of diagnosis has an important value in determining initial response to treatment, remission duration and overall survival (OS) in acute myeloid leukemia (AML). Less is ...known about its value before allogeneic hematopoietic cell transplantation (allo‐HCT) in patients transplanted with active disease, either relapsed or primary refractory (Rel‐Ref) AML. We explored the impact of cytogenetic risk (stratification according to MRC‐UK) in 2089 patients with either Ref (n = 972) or Rel AML (n = 1117) transplanted during the period 2000‐2017. Overall, 154 patients had a favorable risk, 1283 had an intermediate risk and 652 had an adverse cytogenetic risk. Median follow‐up was 49 months. Compared to the favorable risk group, intermediate and adverse risk patients were associated with worse leukemia‐free survival and OS and also with a higher incidence of relapse. In a subgroup analysis of patients in the intermediate risk group harboring Fms‐like tyrosine kinase 3‐internal tandem duplication (FLT3‐ITD), this remained an important prognostic factor, being associated with worse outcomes. When analyzing patients according to the intensity of the conditioning regimen, no differences were observed for the main transplant outcomes. In conclusion, in patients diagnosed with AML and transplanted with active disease, karyotype remains an important prognostic factor, allowing splitting patients into different risk groups according to their cytogenetics. Similarly, FLT3‐ITD mutation also remains a negative prognostic factor in this population.
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.
Allogeneic hematopoietic cell transplantation (allo-HCT) remains a treatment option for patients with chronic myeloid leukemia (CML) who fail to respond to tyrosine kinase inhibitors (TKIs). While ...imatinib seems to have no adverse impact on outcomes after transplant, little is known on the effects of prior use of second-generation TKI (2GTKI). We present the results of a prospective non-interventional study performed by the EBMT on 383 consecutive CML patients previously treated with dasatinib or nilotinib undergoing allo-HCT from 2009 to 2013. The median age was 45 years (18-68). Disease status at transplant was CP1 in 139 patients (38%), AP or >CP1 in 163 (45%), and BC in 59 (16%). The choice of 2GTKI was: 40% dasatinib, 17% nilotinib, and 43% a sequential treatment of dasatinib and nilotinib with or without bosutinib/ponatinib. With a median follow-up of 37 months (1-77), 8% of patients developed either primary or secondary graft failure, 34% acute and 60% chronic GvHD. There were no differences in post-transplant complications between the three different 2GTKI subgroups. Non-relapse mortality was 18% and 24% at 12 months and at 5 years, respectively. Relapse incidence was 36%, overall survival 56% and relapse-free survival 40% at 5 years. No differences in post-transplant outcomes were found between the three different 2GTKI subgroups. This prospective study demonstrates the feasibility of allo-HCT in patients previously treated with 2GTKI with a post-transplant complications rate comparable to that of TKI-naive or imatinib-treated patients.
Allogeneic hematopoietic cell transplantation (alloHCT) is a complex, potentially fatal therapy featuring a myriad of complications. Triggering event(s) of such complications vary significantly, but ...often a so-called "multi-organ failure" (MOF) is reported as the leading cause of death. The identification of the exact trigger of MOF is critical towards early and disease-specific intervention to improve outcome. We examined data from 202 alloHCT patients reported to have died of MOF from the EBMT registry aiming to determine their exact cause of death focusing on veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) due to its life-threatening, often difficult to capture yet preventable nature. We identified a total of 70 patients (35%) for whom VOD/SOS could be considered as trigger for MOF and leading cause of death, among which 48 (69%) were previously undiagnosed. Multivariate analysis highlighted history of hepatic comorbidity or gentuzumab use and disease status beyond CR1 as the only significant factors predictive of VOD/SOS incidence (OR = 6.6; p = 0.001 and OR = 3.3; p = 0.004 respectively). VOD/SOS-related MOF was widely under-reported, accounting for 27% of deaths attributed to MOF of unknown origin without a previous VOD/SOS diagnosis. Our results suggest most missed cases developed late VOD/SOS beyond 21 days post-alloHCT, highlighting the importance of the newly revised EBMT criteria.
After chemotherapy, fewer than 30% of patients with T-cell lymphoma (T-NHL) are long-term disease-free survivors. Thus, there is a growing interest in allogeneic stem cell transplantation (alloSCT) ...and its potential graft-versus-lymphoma effect (GVL) for patient with high-risk or recurrent T-NHL with the aim at providing durable disease control in T-NHL. We conducted this registry study to evaluate the outcome of recipients of alternative donor alloSCT for T-NHL. Patients transplanted with Haploidentical donor (Haplo, n = 41) or Umbilical Cord Blood (UCB, n = 54) were analyzed for overall survival (OS), non-relapse mortality (NRM), relapse, and acute/chronic graft-versus-host disease (aGVHD/cGVHD) incidence. At 2 years, OS and PFS were, respectively, of 59% and 53%, without significant difference between Haplo and UCB. In multivariate analysis, disease status at transplant was an independent risk factor for OS and PFS, and aGVHD III-IV was the main factor for OS and NRM. While no major impact of donor source on survival and mortality was noted, this study suggests that alternative donor transplantation appears feasible and offers benefits to patients with T-cell lymphoma.
•Our short series confirms the high response rate with CPX-351 in t-AML or MRC-AML.•The high rate of MRD negativity supports prior evidence that CPX-351 contributes to long-term remission.•MFC ...monitoring was confirmed as a reliable approach to assess response to treatment.
The phase III study was designed to compare event‐free survival (EFS) after treosulfan‐based conditioning with a widely applied reduced‐intensity conditioning (RIC) busulfan regimen in older or ...comorbid patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplantation (HCT). A previously reported confirmatory interim analysis of the randomized clinical study including 476 patients demonstrated statistically significant noninferiority for treosulfan with clinically meaningful improvement in EFS. Here, the final study results and pre‐specified subgroup analyses of all 570 randomized patients with completed longer‐term follow‐up are presented. Patients presenting HCT‐specific comorbidity index >2 or aged ≥50 years were randomly assigned (1:1) to intravenous (IV) fludarabine with either treosulfan (30 g/m2 IV) or busulfan (6.4 mg/kg IV) after stratification by disease risk group, donor type, and participating institution. The primary endpoint was EFS with disease recurrence, graft failure, or death from any cause as events. EFS of patients (median age 60 years) was superior after treosulfan compared to RIC busulfan: 36‐months‐EFS rate 59.5% (95% CI, 52.2–66.1) vs. 49.7% (95% CI, 43.3–55.7) with a hazard ratio (HR) of 0.64 (95% CI, 0.49–0.84), p = 0.0006. Likewise, overall survival (OS) with treosulfan was superior compared to busulfan: 36‐month‐OS rate 66.8% vs. 56.3%; HR 0.64 (95% CI, 0.48–0.87), p = 0.0037. Post hoc analyses revealed that these differences were consistent with the confirmatory interim analysis, and thereby the treosulfan regimen appears particularly suitable for older AML and MDS patients.
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