Allogeneic Research Articles

A Single-Center Retrospective Evaluation of The Incidence and Survival of Invasive Fungal Infection in Allogeneic Stem Cell Transplant Patients

A Single-Center Retrospective Evaluation of The Incidence and Survival of Invasive Fungal Infection in Allogeneic Stem Cell Transplant Patients

A real-world study on the impact of infection load on mortality in multiple myeloma patients in Finland.

Infections are a clinically significant cause of mortality in multiple myeloma (MM) patients. The high number of infections in MM patients is due to the immunosuppressive effects of the disease itself as well as treatment-related immunosuppression. In this real-world evidence (RWE) study, we used several nationwide healthcare registries of Finland to investigate the effect of infection load on mortality in MM patients during 1997-2021. The highest number of infections was recorded during the first year after MM diagnosis. In patients who received allogenic or autologous stem cell transplantation (ASCT), the number of infections during the first two years post diagnosis was significantly higher than in those treated without ASCT. When compared to their age-, sex-, and region-matched controls, MM patients accrued more infections during the year prior to diagnosis. Intriguingly, patients under 70 years old had significantly more infections already 3 years before diagnosis when compared to their matched controls. Prior to MM diagnosis, the relative proportion of streptococcal septicaemia and pneumonia due to Streptococcus pneumoniae increased the most. Of note, even one recorded infection prior to diagnosis was associated with significantly shorter median overall survival. Importantly, Cox proportional hazard models show that recorded infections both before and after diagnosis increase the independent risk of mortality in MM patients.

Patients' Experiences of Person-Centered Care in the Context of Allogenic Stem Cell Transplantation.

Studies addressing patients' experiences of person-centered care (PCC) in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are scarce; hence, this study aimed to explore patients' experiences of PCC, and its associations with individual characteristics and health-related quality of life, in the context of allogeneic stem cell transplantation. It is a cross-sectional survey study, in patients who had undergone an allo-HSCT at one center in Sweden. The PCC instrument for outpatient care in rheumatology (PCCoc/rheum) was used. Descriptive and analytical statistics were employed. The study had 126 participants, evenly distributed males and females, 18-79 years old (>60% were 50-69 years old), and most were (>70%) married or cohabiting. The sum score for all items on PCCoc/rheum ranged from 20 to 72 (higher score = higher degree of PCC), with a mean value of 62.67 (SD: 9.863). Most participants (87-99%) agreed with the level of person-centeredness for 22 of the 24 items. Of the participants, 83.3% agreed that they had undisturbed conversations, that their problems had been taken seriously (79.0%), that they had an opportunity to tell their story (77.8%), and collaboration with the nurse was good (77.6%). A sizeable proportion disagreed that the care environment was welcoming (11.9%), family members' involvement (13.7%), and the possibility to influence the care (15.5%). The fulfillment of PCC was rated as high, but the results indicate that there is room for improvement regarding the possibility of influencing the care and family members' involvement.

Advanced-Stage Chronic Myeloid Leukemia: Options for Difficult Treatment Situations.

A small number of patients with chronic myeloid leukemia (CML) either present with or progress to the accelerated phase (AP) or blast phase (BP). This occurs in approximately 4-7% of patients with CML. Most patients who progress to BP-CML are of myeloid lineage, while approximately 30% are of lymphoid lineage. Due to the rarity of this condition, there are no large or randomized trials that can inform clinical decisions. Most data are from retrospective chart reviews or data from old studies when tyrosine kinase inhibitors (TKIs) were initially approved. In addition, the definition of these categories has been in continuous flux over the last 20 years, making applicability of data even more confusing. In some classifications, the cutoff is 30% blasts for the definition of BP-CML, while in others a cutoff of 20% is used. In addition, more recently the World Health Organization (WHO) classification omitted the accelerated phase and recognized only a two-phase disease, while the International Consensus Classification retained a three-phase definition and retained the accelerated phase. Therapy for patients with AP/BP-CML depends on several factors, including prior therapy, BCR::ABL1 mutation, co-morbidities, cell lineage, and eligibility for allogeneic stem cell transplantation (alloHCT). Patients with AP-CML at presentation have a relatively favorable prognosis and may not need alloHCT if they respond appropriately to therapy. For patients with AP-CML who progressed while on TKI therapy or those with BP-CML, alloHCT is considered the only curative therapy. Our goal is to review the available data on the therapy of patients with AP-CML and BP-CML.

Treatment of high risk myelodysplastic syndrome.

The myelodysplastic syndrome (MDS) is considered to be a heterogeneous myeloid malignancy with a common origin in the hematopoietic stem cell compartment, generally divided into lower and higher risk. While treatment goal for lower risk MDS (LR-MDS) is to decrease transfusion burden and transformation into acute leukemia major aim for high risk MDS is to prolong survival and ultimately cure. While novel agents such as luspatercept or imetelstat have recently been approved as new treatment options for LR-MDS, hypomethylating agents (HMA) remain currently the only approved non-transplant option for HR-MDS and is the standard of care for non-transplant-eligible patients. Combinations with other drugs as first-line treatment has to date not proven more efficacious than monotherapy in HR-MDS, and outcome after HMA failure is poor. The only potential cure and standard of care for eligible patients is allogeneic stem cell transplantation (HSCT) and even if the number of transplanted - especially older - MDS patients increased over time due to a better management and donor availability the majority of MDS patients will not be eligible for this curative approach. Current challenges encompass to decrease the relapse risk, the main cause of HSCT failure. This review will summarize current knowledge of options of transplant- and non-transplant treatment approaches for these patients and demonstrate the unmet clinical need for more effective therapies.

Intestinal perforation following allogeneic stem cell transplantation caused by Epstein-Barr virus-positive mucocutaneous ulcer.

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Posttransplant Erythrocytosis after Allogenic Stem Cell Transplant for Acute Myeloid Leukemia: A Case Report and Review of Literature

Posttransplant Erythrocytosis after Allogenic Stem Cell Transplant for Acute Myeloid Leukemia: A Case Report and Review of Literature

Updates in novel immunotherapeutic strategies for relapsed/refractory AML.

Acute myeloid leukemia (AML) is a severe hematological malignancy with poor outcomes, particularly in older adults. Traditional treatment options like high-dose chemotherapy often lead to refractory or relapsed AML, with even worse outcomes. New therapies for relapsed and refractory AML are needed, and this review explores the most recent advancements in immunotherapy in AML. Checkpoint Inhibitors utilizing innate or adaptive immune targeting have shown potential to improve AML outcomes when combined with hypomethylating agents and chemotherapy. The use of adoptive cell therapy in AML demonstrates promising early data, however, there is a need for better target selection. Although early in development, both vaccine therapy as well as stimulator of interferon genes (STING) agonists have potential to enhance the innate immune response to overcome AML's immune evasion. Immunotherapy has become a promising approach for AML treatment, especially in refractory and relapsed AML, especially in patients who are not eligible for allogeneic stem cell transplants. Future research should focus on a deeper understanding of the immune microenvironment to identify the most critical targets for optimization, as well as personalized therapeutic combination strategies. Here we present a comprehensive overview of the recent developments in immunotherapy for relapsed and refractory AML.

DNA barcoded peptide-MHC multimers to measure and monitor minor histocompatibility antigen-specific T cells after allogeneic stem cell transplantation

Allogeneic stem cell transplantation (alloSCT) provides a curative treatment option for hematological malignancies. After HLA-matched alloSCT, donor-derived T cells recognize minor histocompatibility antigens (MiHAs), which are polymorphic peptides presented by...

Health-related values discussions with patients undergoing allogeneic and autologous stem cell transplant: Feasibility and acceptability of an early primary palliative care intervention

Health-related values discussions with patients undergoing allogeneic and autologous stem cell transplant: Feasibility and acceptability of an early primary palliative care intervention

Haematopoietic gene therapy of non-conditioned patients with Fanconi anaemia-A: results from open-label phase 1/2 (FANCOLEN-1) and long-term clinical trials

Allogeneic haematopoietic stem-cell transplantation is the standard treatment for bone marrow failure (BMF) in patients with Fanconi anaemia, but transplantation-associated complications such as an increased incidence of subsequent cancer are frequent. The aim of this study was to evaluate the safety and efficacy of the infusion of autologous gene-corrected haematopoietic stem cells as an alternative therapy for these patients. This was an open-label, investigator-initiated phase 1/2 clinical trial (FANCOLEN-1) and long-term follow-up trial (up to 7 years post-treatment) in Spain. Mobilised peripheral blood (PB) CD34+ cells from nine patients with Fanconi anaemia-A in the early stages of BMF were transduced with a therapeutic FANCA-encoding lentiviral vector and re-infused without any cytotoxic conditioning treatment. The primary efficacy endpoint of FANCOLEN-1 was the engraftment of transduced cells, as defined by the detection of at least 0·1 therapeutic vector copies per nucleated cell of patient bone marrow (BM) or PB at the second year post-infusion, without this percentage having declined substantially over the previous year. The safety coprimary endpoint was adverse events during the 3 years after infusion. The completed open-label phase 1/2 and the ongoing long-term clinical trials are registered with ClinicalTrials.gov, NCT03157804; EudraCT, 2011-006100-12; and NCT04437771, respectively. There were eight evaluable treated patients with Fanconi anaemia-A. Patients were recruited between Jan 7, 2016 and April 3, 2019. The primary endpoint was met in five of the eight evaluable patients (62·50%). The median number of therapeutic vector copies per nucleated cell of patient BM and PB at the second year post-infusion was 0·18 (IQR 0·01-0·20) and 0·06 (0·01-0·19), respectively. No genotoxic events related to the gene therapy were observed. Most treatment-emergent adverse events (TEAEs) were non-serious and assessed as not related to therapeutic FANCA-encoding lentiviral vector. Nine serious adverse events (grade 3-4) were reported in six patients, one was considered related to medicinal product infusion, and all resolved without sequelae. Cytopenias and viral infections (common childhood illnesses) were the most frequently reported TEAEs. These results show for the first time that haematopoietic gene therapy without genotoxic conditioning enables sustained engraftment and reversal of BMF progression in patients with Fanconi anaemia. European Commission, Instituto de Salud Carlos III, and Rocket Pharmaceuticals.

Maintenance strategies for relapse prevention and treatment.

Posttransplant relapse is the most significant challenge in allogeneic stem cell transplantation (alloSCT). Posttransplant interventions, in conjunction with optimal conditioning regimens and donor selection, are increasingly supported by evidence for their potential to prolong patient survival by promoting antileukemia or graft-versus-leukemia effects. Our review begins by highlighting the current evidence supporting maintenance therapy for relapse prevention in acute myeloid leukemia and acute lymphocytic leukemia. This includes a broad spectrum of strategies, such as targeted therapies, hypomethylating agents, venetoclax, and immunotherapies. We then shift our focus to the role of disease monitoring after alloSCT, emphasizing the potential importance of early detection of measurable residual disease and a drop in donor chimerism. We also provide an overview of salvage therapies for overt relapse, including targeted therapies, chemotherapies, immunotherapies, donor lymphocyte infusion, and selected agents under investigation in ongoing clinical trials. Finally, we review the evidence for a second alloSCT (HSCT2) and discuss factors that impact donor selection for HSCT2.

Relapsed/refractory CLL: the role of allo-SCT, CAR-T, and T-cell engagers.

Chronic lymphocytic leukemia (CLL) patients who are refractory to both Bruton's tyrosine kinase and B-cell/CLL lymphoma 2 (BCL2) inhibitors face a significant treatment challenge, with limited and short-lasting disease control options. This underscores the urgent need for novel therapeutic strategies. Immunotherapy has emerged as a promising approach to address this unmet need, offering the potential for durable remissions and improved patient outcomes. Historically, allogeneic stem cell transplantation has been used for high-risk CLL patients, demonstrating promising survival rates. However, its applicability is limited by high treatment-related mortality and chronic graft-versus-host disease, especially in older and frail patients. Chimeric antigen receptor (CAR) T-cell therapy is gaining attention for its potential in relapsed/refractory CLL. Early clinical trials have shown that CAR T cells can induce durable remissions, with encouraging overall response rates in heavily pretreated patients. Additionally, bispecific antibodies are being explored as immunotherapeutic strategies, showing promising preclinical and early clinical results in targeting CLL cells effectively. One of the major challenges in CLL treatment with T-cell-based therapies is the acquired T-cell dysfunction observed in patients. To overcome these limitations, strategies such as combining targeted agents with cellular immunotherapies, modifying CAR designs, and incorporating immunomodulatory compounds into the manufacturing process are being investigated. These innovative approaches aim to enhance T-cell engagement and improve outcomes for CLL patients, offering hope for more effective and sustainable treatments in the future.

Outcome of Cerebral Vasculopathy and Cognitive Performances 10 Years Post-Enrollment in the Drepagreffe Trial Comparing Allogeneic Stem Cell Transplantation to Standard-Care in Children with Sickle Cell Anemia and History of Abnormal Cerebral Velocities

DREPAGREFFE-1 (NCT01340404), was the first prospective trial comparing allogeneic stem cell transplantation (alloSCT) to standard-of-care (SoC) in children with sickle cell anemia (SCA). This French multicenter trial was defined by the random-availability of a matched-sibling donor (MSD). Inclusion criteria were SS/Sb0 children (5-15yr) placed on long-term chronic-transfusion (CT) for a history of abnormal cerebral arterial velocities (TAMMV≥200 cm/sec), with at least one non-SCA sibling, and parents accepting HLA-typing and alloSCT if an MSD was available.Sixty-seven children (35F/32M), including 7 with stroke-history, were enrolled (Dec-2010/June-2013). Children with MSD (n=32) were transplanted, while those without (n=35) were maintained on CT for at least one year and then switched to hydroxyurea (HU) if normalized TAMMVs and no stenosis. Results at 1 and 3 years were reported (Bernaudin et al JAMA. 2019;321(3); Verlhac et al Br J Haematol. 2021;193(1)). As a reminder, comparing alloSCT vs. SoC at 1 yr, the highest TAMMVs (primary outcome) were significantly lower after alloSCT than under SoC (difference -40.8 cm/s; [95%CI:-62.9;-18.6]; P<.001). At 3 years, the highest TAMMVs were lower, the proportion of patients with normalized-TAMMVs was higher, the stenosis score in stroke-free patients was lower, and the quality of life (QoL) was better for physical and school functioning. Nevertheless, no significant difference in ischemic lesions and cognitive performance was observed.DREPAGREFFE-2 trial (NCT 05053932), supported by ABM and Pfizer, aimed to reevaluate at 10yr the 67 SCA-children (Sept-2022/Aug-2024) to test whether the differences in cognitive performance and ischemic lesions had changed significantly. Events and treatment changes since Year 3 were routinely recorded. Clinical evaluation, routine biological check-up, Intracranial and cervical-color Doppler-ultrasound, cerebral MRI/MRA/neck-MRA were performed. Non-opposition consent was required for cognitive testing (WISC-V and WAIS-IV), biological research, and QoL (PedsQLTM) assessment. Death and stroke did not occur in either arm.In the alloSCT arm (n=32), follow-up ended at 7.0 and 7.9 years for 2 children with full donor-chimerism and no chGvHD, due to return to Africa and UK. At 10yr, median (range) donor-chimerism was 92.5% (19%-100%) and no chGvHD was observed.In the SoC arm (n=35), 23 patients with normalized velocities and no stenosis under CT were switched to HU. At 10yr, 17 are still on HU, 15 are on CT, and 3 had related haploIdentical-SCT at 6.7, 7.2 and 9.3yr post-enrollment. They are well, one having only mild chGvHD. Two patients still on CT for stroke-history did not give consent for research analyses.Including the 3 haplo-SCT with the alloSCT-arm for analysis at 10yr, Hb and HbA% were higher while HbS%, Retic., WBC, neutro, bilirubin, LDH, and ferritin were lower in the alloSCT vs. SoC arm (P<.001 for all).Available mean (SD) QoL at 10yr in alloSCT (n=25) vs. SoC (n=28) was not different for emotional but higher for physical (84.0 (16.3) vs 76.4 (11.2); P=.013), school (72.6 (17.2) vs 61.4 (14.7);P=.016) and even social functioning (93.8 (10.7) vs. 86.4 (12.9); P=.003).MRI/MRA and cognitive performance data were only analyzed in stroke-free patients. At enrollment (T0), silent cerebral infarcts (SCI) were present in 6/31 in the SoC-arm and 12/28 in the alloSCT arm. At 10yr, 5 additional patients had developed SCI in the SoC arm, but none did in the alloSCT, while SCI were either no more visible or <3mm in 1 (SoC) and 4 patients (alloSCT) (P=.010). Comparing alloSCT (n=24) to SoC (n=21), cognitive testing showed no difference in verbal comprehension and perceptual reasoning index, while the mean (SD) working memory index (WMI) was higher (89.6 (11.8) vs 80.5 (10.8); P=.021) with a digit span of 8.4 (1.9) vs. 6.7 (1.8)(P=.005), the processing speed index (PSI) was higher (96.5 (21.9) vs. 83.7 (14.4);P=.035) with a symbol search of 9.3 (2.0) vs. 7.3 (2.9)(P=.021), respectively. Compared to T0, mean (SD) WMI and PSI at 10yr improved, although not significantly, in transplanted patients [+5.8 (15.6) vs. +9.0 (25.4)] but not in the SoC arm [-2.0 (15.7) and +0.6 (19.7)].Thus, this first prospective comparative trial demonstrates that differences between alloSCT and SoC changed significantly at 10yr with alloSCT providing better primary prevention of SCI, social QoL, working memory and processing speed

The time factor and the allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia

Introduction. The current overall effectiveness of acute myeloid leukemia (AML) treatment is largely ensured by the integration of transplantation technologies, but not all patients who are indicated to undergo transplantation of allogeneic hematopoietic stem cells (allo-HSCT) can reach this stage.Aim: to analyze the time and volume of the implementation of allo-HSCT in patients with AML in the first complete remission (1CR).Materials and methods. Between January 2020 and December 2023, 477 AML patients from 43 different regions of the Russian Federation were referred to the NMRC for Hematology for the possibility of performing allo-HSCT. In this cohort of patients, the following time parameters were analyzed: days from diagnosis of AML to primary treatment at the transplant center, from primary treatment to search for a donor (related or non-related), from diagnosis of AML to allo-HSCT, from the achievement of 1CR to allo-HSCT.Results. 175 (36.7 %) patients, agreed upon by the Transplant Commission, were selected to undergo allo-HSCT. Of these, only 163 patients, who had allo-HSCT performed before January 2024, were included in further analysis. It was not possible to implement allo-HSCT in the other 236 agreed upon cases due to the following reasons: refusal of the patient — 110 (46.6 %), relapse — 48 (20.3 %) patients, death — 23 (9.7 %) patients. Median time from 1CR to allo-HSCT was 6.8 (0.3– 26) months for all patients: for a related fully compatible donor 5.8 (0.5–26.0) months, for a haploid donor — 6.1 (0.3–23.5) months, in case of non-related — 8.0 (0.6–8.6) months. In 5 years, the NMRC for Hematology managed to reduce the time to the general allo-HSCT in 1CR for patients with AML from 6.5 months in 2018 to 5.8 months in 2023. Also, under the current “AML-21” protocol, the time from 1CR to allo-HSCT in patients included in the multicenter study was minimized to — 4.8 (0.33–11.0) months, and for AML patients from the poor prognosis group — 3.4 (0.33–8.0 months).Conclusion. In addition to achieving full, optimally — MDR-negative remission, the absence of severe concomitant pathology, and the presence of a donor, the time factor must also be considered. In order to cure more AML patients, it is necessary to bring the implementation of allo-HSCT to the earliest possible date after achieving 1CR.

Dynamics of measurable residual disease for risk stratification and guiding allogeneic transplant in acute myeloid leukaemia patients with myelodysplasia-related mutations in first remission.

Accurate classification and risk prediction are critical for therapeutic decision-making in patients with acute myeloid leukaemia (AML). Myelodysplasia-related (MR) gene mutations are classified as adverse genetic factors by the European LeukaemiaNet-2022 guidelines. However, their prognostic value in de novo AML remains controversial. This study retrospectively analysed 188 patients with de novo AML-MR, stratifying them into four subgroups based on dynamic measurable residual disease (MRD) after induction, one or two courses of consolidation chemotherapy. The median follow-up was 36.8 months (4.6-73.7). Patients with persistent or recurrent MRD positivity after the second consolidation had the poorest 3-year relapse-free survival (RFS), overall survival (OS) and cumulative incidence of relapse compared to the other groups (p < 0.001). Multivariable analysis identified this high-risk group as an independent risk factor for both RFS and OS. We observed significant heterogeneity of OS benefit from allogeneic stem cell transplantation (allo-SCT) by MRD-risk groups, with substantial OS advantage for patients in subgroup D (3-year OS: allo-SCT 70.0% vs. 18.2% without, p < 0.001) but no benefit for others (p = 0.047 for interaction). This study underscores the importance of dynamic MRD in refining risk stratification and identifying de novo AML patients with MR mutations who would benefit from allo-SCT during the first complete remission.

Impact of treosulfan exposure on clinical outcome after allogeneic stem cell transplantation in children: A substudy of 2 phase 2 trials.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a vital treatment for various paediatric malignant and nonmalignant diseases. The conditioning treatment before allo-HSCT is crucial for successful engraftment. Treosulfan, a cytotoxic prodrug, has gained popularity due to its lower toxicity compared to traditional alkylating agents used for conditioning treatment. We investigated the relationship between pharmacokinetics and pharmacodynamics of treosulfan in paediatric patients, in a substudy pooling from 2 multicentre phase 2 clinical trials. A total of 83 children with malignant and nonmalignant diseases received treosulfan-based conditioning. Treosulfan exposure and its relationship with clinical outcomes, including survival, graft failure and graft-vs.-host disease, were investigated. Our findings reveal no significant association between treosulfan exposure and the key clinical outcomes or toxicity (P-values between .22 and .99), if the dosing is based on the approved product information. These findings suggest that treosulfan exposure after standardized body surface area-based dosing is appropriate in paediatric allo-HSCT.

Graft-versus-host disease after anti-CD19 chimeric antigen receptor T-cell therapy following allogeneic hematopoietic cell transplantation: a transplant complications and paediatric diseases working parties joint EBMT study.

In patients diagnosed with B-acute lymphoblastic leukemia (B-ALL) or B-non-Hodgkin's lymphoma (B-NHL) relapsing after allogeneic stem cell transplantation (allo-HCT), it is a standard practice to perform anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. When collected from the patient after allo-HCT, the produced CAR-T cells are likely to be donor T-cell-derived, creating unknown safety risks due to their potential allo-reactivity. We therefore performed an EBMT registry-based study on the incidence of graft-versus-host disease (GvHD) in this setting. We included 257 allo-HCT patients (n = 172 ≥ 18 years) with B-ALL or B-NHL, treated with anti-CD19 CAR T-cells (tisagenlecleucel n = 184, brexucabtagene autoleucel n = 43 and axicabtagene ciloleucel n = 30), between 2018 and 2022. Three patients developed aGvHD, whereas 6 patients developed cGvHD after CAR T-cell. The 100-day cumulative incidence (CI) of new aGvHD was 1.6% and the 12-month CI of new cGvHD was 2.8%. The 1-year GvHD relapse-free survival and non-relapse mortality were 52.1% and 4.7%, respectively. Last, with a median follow up of 18.8 months, the 1-year overall survival was 76.8%. In summary, the GvHD rate in allo-HCT patients treated with CAR T-cell therapy is relatively low. Our data support the view that GvHD is not a major safety issue in this setting.

The role of allogeneic stem cell transplantation in acute myeloid leukemia with translocation t(8;16)(p11;p13).

Acute myeloid leukemia (AML) with translocation t(8;16)(p11;p13) represents a rare entity that has been categorized as a disease-defining recurring cytogenetic abnormality with adverse risk in the 2022 European LeukemiaNet classification. This rating was mainly based on a retrospective analysis comprising patients from several large clinical trials, which, however, included only 21 patients treated with allogeneic stem cell transplantation (alloSCT). Therefore, the European Society for Blood and Marrow Transplantation performed a registry study on a larger cohort to evaluate the role of alloSCT in t(8;16) AML. Sixty transplant recipients with t(8;16) AML were identified. Two-year overall and leukemia-free survival (OS/LFS) was 43/39%. Patients transplanted in first complete remission (CR1, n = 44) achieved a 2-year OS/LFS of 48%/48%. Following alloSCT in CR1, the multivariable analysis identified a complex karyotype (CK) as a major risk factor for relapse (HR 4.17, p = .016), lower LFS (HR 3.38, p = .01), and lower OS (HR 3.08, p = .017). Two-year OS/LFS of patients with CK was 19%/19%, in contrast to 67%/67% in patients with t(8;16) outside a CK. Other factors for inferior outcomes were older age and secondary AML. In summary, alloSCT could mitigate the adverse risk of patients with t(8;16) AML not harboring a CK, particularly when performed in CR1.

Pretransplantation risk factors for positive MRD after allogeneic stem cell transplantation in AML patients: a prospective study.

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.