Myeloid sarcoma (MS) is a rare hematological neoplasm with poor prognosis, posing a significant clinical challenge due to the absence of effective and standardized treatments. We conducted a retrospective analysis of 162 MS patients treated at 12 centers to compare outcomes between intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our analysis revealed that allo-HSCT demonstrated superior overall survival (OS) within the initial 36 months compared to intensive chemotherapy alone (p = 0.037). However, beyond 36 months (36-60 months), a reverse trend was observed (p = 0.056). Subgroup analysis revealed potential benefit for isolated MS patients with allo-HSCT, but not for those with leukemic MS. Additionally, in patients achieving first complete remission (CR1) after induction chemotherapy, allo-HSCT did not significantly improve 5-year OS compared with intensive chemotherapy alone (p = 0.25). Conversely, allo-HSCT significantly improved 5-year OS in non-CR1 patients (p < 0.001). Notably, HLA-matched HSCT and haploidentical HSCT showed comparable outcomes in terms of OS, disease-free survival, and cumulative incidence of relapse. In conclusion, allo-HSCT improved outcomes for MS patients within 36 months of disease onset, and haploidentical HSCT emerged as a viable treatment option for patients without matched donors.

We aimed to prospectively explore the risk factors for measurable residual disease (MRD) positivity after allogeneic stem cell transplantation (allo-SCT) in AML patients (n = 478). The cumulative incidences (CIs) of post-SCT MRD positivity at 100 days, 360 days and 3 years were 4.6%, 12.1% and 18.3%, respectively. Positive pre-SCT MRD and pre-SCT active disease were risk factors for post-SCT MRD positivity at both 360 days and 3 years (P < 0.001). European LeukemiaNet (ELN) 2017 risk stratification was a risk factor for positive post-SCT MRD at 360 days (P = 0.044). A scoring system for predicting post-SCT MRD positivity at 360 days was established by using pre-SCT MRD, pre-SCT active disease and ELN 2017 risk stratification. The CI of positive post-SCT MRD at 3 years was 13.2%, 23.7%, and 43.9% for patients with scores of 0, 1, and 2, respectively (P < 0.001). Multivariate analysis demonstrated that the scoring system was associated with a higher CI of post-SCT MRD positivity, leukemia relapse and inferior survival. Our data indicate that positive pre-SCT MRD status, pre-SCT active disease, and ELN 2017 risk stratification are risk factors for positive post-SCT MRD status in AML patients.

Measurable residual disease (MRD) testing in patients with acute myelogenous leukemia (AML) represents a heterogenous assessment process designed to quantify leukemia-specific biomarkers that are not ascertainable by routine pathologic evaluation. The most common tools used to assess MRD are multiparameter flow cytometry (MPFC), and polymerase chain reaction (PCR) based tools, including quantitative or digital droplet PCR (qPCR, ddPCR), or next-generation sequencing (NGS) technologies. Collectively, MRD assessments have become an important clinical tool in the management of patients with AML. Despite progress, significant questions remain with respect to the appropriate timing, frequency, and methodology of MRD assessment, and whether or how to adapt therapy based on MRD results. Recent data from the Pre-MEASURE study, a retrospective cohort analysis of error corrected NGS based MRD assessment prior to allogeneic hematopoietic cell transplantation (alloHCT) in patients with AML, provides additional key information with respect to the emerging role of NGS-based technology in MRD assessment. In the context of this review, we evaluate the Pre-MEASURE study as well as other recent, high-quality assessments of MRD in AML. Our focus is to provide a practical assessment of the use of emerging MRD technologies in patients with AML with an emphasis on the role of peri-transplant MRD for the practicing clinician.

Pure red cell aplasia (PRCA) and autoimmune hemolytic anemia (AIHA) post-hematopoietic stem cell transplantation (HSCT) are an unmet medical need with no established standard of care, significantly affecting the patient quality of life and posing a challenge for clinicians. The anti-CD38 IgG-kappa Daratumumab appears to be a safe and efficace treatment compared to prior drugs. Our study is a prospective monocentric investigation assessing the use of daratumumab in these complications following allo-HSCT. Here we describe our experience on six patients with a median age of 65 years. All treated patients, except one, who died because of sepsis during GVHD exacerbation, reached transfusion independence with erythropoietin suspension. Poor graft function remains a management challenge for clinicians and has a significant impact on the patient's quality of life. Currently, therapeutic options for PRCA and for the least common AIHA, appear ineffective, making it difficult to address the diverse needs of post-transplant patients. Although our data and those previously reported in the literature are preliminary, daratumumab prompts further reflection on its use in this setting of patients.

We looked at treatment rates and center density across countries for patients treated in 2022; 46,143 HCTs (19,011 (41.2%) allogeneic, 27,132 (58.8%) autologous) reported by 689 centers. 4329 patients received advanced cellular therapies, 3205 were CAR-T. We found considerable differences in utilization of autologous, allogeneic HCT and more so for CAR-T. Differences in procedure type and for allogeneic HCT in donor use and disease indication are highlighted. For instance, countries with the highest use of unrelated donors per 10 million inhabitants were Germany (297) and the Netherlands (230), for identical sibling HCT it was Israel (148) and Lebanon (113), for haploidentical it was Israel (94) and Italy (94) and for cord blood it was the Netherlands (24) and the United Kingdom (15). We looked at HCT use for specific indications in allogeneic HCT (AML CR1, MDS, MPN and BMF). We correlated treatment rates with GNI and with demographic age structure and show correlations in HCT and CAR-T use and center density, highest in Italy for allogeneic and autologous HCT and in Switzerland for CAR-T. Resource restricted countries tend to concentrate HCT use in a limited number of centers. These data are useful for comparisons across countries.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy and the only curable therapy is allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, allo-HSCT is not appropriate for all CMML patients, and relapse is the leading cause of treatment failure. This project conducted a nationwide multicenter real-world study to develop a novel prediction scoring system for early relapse. A total of 238 CMML patients from twenty-seven medical centers treated with allo-HSCT, and 307 adult patients with CMML who underwent allo-HSCT in a publicly available research dataset from the Center for International Blood and Marrow Transplantation Registry (CIBMTR) database were included. Independent prognostic factors for the early relapse of CMML posttransplantation were identified according to competing risk regression methods. Four prognostic factors were identified: bone marrow blasts >10% (hazard ratio [HR], 4.262; P = 0.014), age >60 years (HR, 6.221; P = 0.007), hemoglobin level <100 g/L (HR, 3.695; P = 0.004), and non TET2 gene mutation (HR, 3.425; P = 0.017). A risk-grading scoring system was developed based on the regression coefficients and patients were stratified into low-risk (0-1 point), intermediate-risk (1.5-2 points) and high-risk ( > 2 points) groups. The validated internal c-statistic was 0.767 (95% confidence interval [CI], 0.674-0.860), and the external c-statistic was 0.769 (95% CI, 0.703-0.836). In the derivation cohort, the cumulative incidence rates of early relapse in the low-risk, intermediate-risk, and high-risk groups were 1.35% (95% CI: 1-4%), 10.40% (95% CI: 4-16%), and 29.54% (95% CI: 16-39%) (P < 0.001), respectively. This scoring system can be utilized to early identification of patients at a high risk of relapse and contributing to the implementation of urgent medical support.

In fit patients with newly diagnosed myeloma, high-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is considered standard of care. For mobilization of CD34+ cells for ASCT, combined cytotoxic chemotherapy and G-CSF is commonly used. However, the importance of cytostatic chemotherapy for reliable mobilization remains unclear. This prospective randomized phase II non-inferiority trial compared G-GSF only (G) compared to standard chemotherapy/G-CSF (CG) for CD34+ mobilization. The primary endpoint was a less than 15% difference in successful stem cell collection ( ≥ 5.0 × 10 CD34+ cells/kg b.w. in a single day collection procedure without additional stimulation with plerixafor) with the G regimen. 136 patients were 1:1 randomized. With an 18% difference in favor of the CG therapy, the non-inferiority margin was not maintained (95% CI 1%, 34%, p = 0.04). The median total CD34+ yield was 9.99 × 10/kg b.w. in CG patients and 7.42 × 10/kg b.w. in patients with G-CSF alone (p < 0.001). Ultimately, 130 (96%) patients proceeded to HDCT with ASCT. There were no differences in adverse events, hematologic engraftment, quality of life, or pain perception between the groups. Our data indicate that G-CSF only is inferior to chemotherapy with G-CSF for peripheral CD34+ stem cell mobilization. Trial registration SNCTP #: SNCTP000002952; Trials.gov #: NCT03442673.

Immunological reconstitution after allogeneic hematopoietic cell transplantation (alloHCT) is critical for patient survival. We compared short- and long-term immune reconstitution and clinical endpoints in adult recipients of haploidentical or mismatched T cell replete peripheral blood stem cell transplants (PBSCT) with post-transplant cyclophosphamide as GvHD prophylaxis (PTCY, n = 68) to: (a) patients receiving matched unrelated grafts and anti-T lymphocyte globulin (ATLG) (MUD/ATLG, n = 280); (b) patients with a mismatched donor and ATLG (MM/ATLG, n = 54); and (c) recipients of matched related grafts without ATLG (MRD/NoATLG, n = 97). PTCY was associated with delayed neutrophil engraftment, low NK-cell counts on day 30 and reduced CD8+ cells on days 60-80. In terms of long-term reconstitution, PTCY recipients demonstrated significantly higher CD4+ counts from day 100-365, primarily derived from naïve T cells. Additionally, B-lymphocyte counts at one year were highest in the PTCY group. Early morbidity and mortality due to infectious complications (viral reactivation, (blood stream) infections) were most frequent in PTCY patients during the first three months. However, beyond three months, no PTCY patient suffered a fatal infection. Our study highlights the pattern of early immunodeficiency followed by robust long-term immune reconstitution in PTCY recipients, identifying critical time periods of risk that could be targeted to optimise patient survival and reduce infectious complications.

NPM1 mutated acute myeloid leukemia (AML) comprises roughly 30% of all AML cases and is mainly classified as favorable or intermediate-risk according to the European Leukemia Net stratification. Some patients, however, either have a poor response to initial intensive chemotherapy or ultimately relapse. NPM1 mutations are common, generally stable at early relapse and AML specific, features which make them ideal targets for measurable residual disease (MRD) monitoring. MRD monitoring via molecular analysis during the course of treatment can inform the role of allogeneic stem cell transplantation (HCT) in first remission in patients with NPM1 mutated AML with high-risk co-occurring mutations, particularly FLT3-ITD, and in favorable risk patients who do not achieve defined molecular milestones. In this review, we evaluate the prognostic role of MRD monitoring in NPM1 mutated AML and its use as a predictive biomarker to refine risk stratification and inform decision making regarding treatment. We explore the impact of pre-HCT MRD positivity on post-HCT outcomes in this AML subset, and how HCT-related factors such as conditioning intensity may influence this risk.

Despite its indolent evolution, vitreoretinal lymphoma (VRL) has a poor prognosis due to a major risk of relapse in the central nervous system (CNS) and may necessitate aggressive therapy. However, the use of high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) is poorly documented. We retrospectively analysed from the French LOC network database the adult immunocompetent patients treated with HCT-ASCT for isolated VRL. Thirty-eight patients underwent consolidation with HCT-ASCT for isolated VRL between 2008 and 2019 after induction chemotherapy. Twenty patients had primary VRL, and 18 had an isolated VRL relapse of a primary CNS lymphoma. Three patients underwent HCT-ASCT in first-line treatment, 24 in second-line treatment, and 11 in subsequent lines. At HCT-ASCT, the median age was 61 years, and the median KPS was 90. Thirty-two patients (84%) received high-dose thiotepa-based HCT. One patient (3%) died from HCT-ASCT toxicity. Nineteen (50%) patients relapsed after HCT-ASCT, including 17 cases occurring in the brain. The median progression-free survival, brain-free survival and overall survival from HCT-ASCT were 96, 113 and 92 months, respectively. HCT-ASCT represents an effective therapeutic strategy for select VRL patients, with a tolerable safety profile. However, the risk of subsequent brain relapse remains significant.

Several CD19 CAR-T-cell drugs are approved for safety and efficacy in advanced B-cell cancers with encouraging results. However, primary refractory and relapse are common. We critically analyze long-term data on efficacy of CD19 CAR-T-cell therapies in B-cell non-Hodgkin lymphomas from clinical trials with those of so-called real world data. We identify co-variates associated with efficacy, discuss mechanisms of relapse, summarize the data on the results of post-failure therapy including allotransplants, monoclonal and bi-specific antibodies, antibody-drug conjugates, immune checkpoint-inhibitors and repeat infusions of CAR-T-cells. We conclude, save for allotransplants, there are few data strongly supporting any of these interventions. Most trial are with few heterogeneously-treated subjects with diverse interventions and brief follow-up. Interventions need to be tailored to the cause(s) of CAR-T-cell failure. Prestly, there is not a convincingly safe and effective therapy of people failing initial CAR-T-cell therapy of B-cell non-Hodgkin lymphoma.