alloSCT In CR1 Research Articles

Allogeneic stem cell transplantation in de novo core-binding factor acute myeloid leukemia in first complete remission: data from the EBMT.

Core-binding factor acute myeloid leukemia (CBF-AML) represents 12-15% of all AML cases. Although CBF positivity infers a survival advantage, overall survival (OS) remains dismal. Treatment is with cytarabine/anthracycline-based chemotherapy induction followed by high-dose cytarabine (HiDAC) consolidation. Allogeneic hematopoietic stem cell transplantation (allo-SCT) is reserved for relapse or for patients having not achieved MRD-negativity at high risk for relapse. The role of SCT in first complete remission (CR1) remains controversial and is considered in high risk conditions. In this retrospective, multi-national, European Society for Blood and Marrow Transplantation (EBMT)-based study, we identified 1901 patients with de novo CBF-AML who received an allo-SCT or autologous transplantation (ASCT) in CR1. 65.5% harbored t(8;21) and 34.4% inv(16). In this group, the majority (77%) were treated with allo-SCT in CR1. In multivariate analysis, treatment with allo-SCT was an independent and significant, negative predictor of NRM and OS (HR 4.26, p < 0.0001 and HR 1.67, p = 0.003) and among patients treated with allo-SCT, those treated with MSD had the best outcomes, comparable to those treated with ASCT.There was no interaction between the type of transplant and MRD status at time of SCT. In both, MRD-negative and MRD-positive groups, NRM was worse in the allo-SCT group (MRD-: 12.9% vs 5.2%, p = 0.007; MRD+: 10.6% vs 0%, p = 0.004). We therefore demonstrated that consolidation in CR1 with allo-SCT results in worse outcomes than ASCT. Whether consolidation with ASCT yields better outcomes than chemotherapy alone or chemotherapy in combination with Gemtuzumab Ozogamicin is yet to be investigated.

Utility of allogeneic stem cell transplantation for adult Ph+ALL with complete molecular remission.

This study aimed to investigate the usefulness of allogeneic stem cell transplantation (allo-SCT) for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) in the first complete remission (CR1) with complete molecular remission (CMR). We compared the outcomes between Ph+ALL patients who did or did not undergo allo-SCT in CR1. We included patients enrolled in the prospective clinical studies in the tyrosine kinase inhibitor era conducted by the Japan Adult Leukemia Study Group, who achieved CMR within 3 months. A total of 147 patients (allo-SCT: 101; non-SCT: 46) were eligible for this analysis. In the multivariate analyses, allo-SCT was significantly associated with both superior overall survival (OS) (adjusted hazard ratio (aHR): 0.54; 95% CI: 0.30-0.97; p = .04) and relapse-free survival (RFS) (aHR: 0.21; 95% CI: 0.12-0.38; p < .001). The 5-year adjusted OS and RFS were 73% and 70% in the allo-SCT cohort, whereas they were 50% and 20% in the non-SCT cohort. Despite the higher non-relapse mortality (aHR: 3.49; 95% CI: 1.17-10.4; p = .03), allo-SCT was significantly associated with a lower relapse rate (aHR: 0.10; 95% CI: 0.05-0.20; p < .001). In addition, allo-SCT was also associated with superior graft-versus-host disease-free, relapse-free survival (aHR: 0.43; 95% CI: 0.25-0.74; p = .002). Propensity score-matched analyses confirmed the results of the multivariate analyses. In patients who achieved CMR within 3 months, allo-SCT in CR1 had superior survival and lower relapse compared with the non-SCT cohort.

Real-World Outcomes with CPX-351 Induction in Adults with Newly Diagnosed Acute Myeloid Leukemia

Introduction: CPX-351 is a dual-drug liposomal encapsulation of daunorubicin and cytarabine with a fixed molar ratio of 1:5. CPX-351 is approved for the treatment of newly diagnosed, therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia related changes (AML-MRC) in the U.S. and Europe for adult patients (pts) eligible for intensive chemotherapy. In a randomized phase 3 study of older pts ages 60-75, CPX-351 induction showed improved CR rates and OS compared to conventional 7+3 induction, with the greatest benefit seen in pts with t-AML and those without prior hypomethylating agent (HMA) use. There is limited data on the use of CPX-351 in younger pts, although the U.S. FDA approval was not age-restricted. This study examined real-world CPX-351 usage, including patient selection, clinical outcomes, and complications during induction hospitalizations. Methods: We identified previously untreated AML pts who received CPX-351 induction chemotherapy at the University of Kansas Medical Center via retrospective chart review from August 2017 - May 2023. Determination of t-AML and AML-MRC was made by patient history, bone marrow morphology, and available cytogenetic and molecular information at the time of therapy selection. We excluded pts who received CPX-351 as part of a clinical trial. Data was collected for baseline demographics, disease characteristics, outcomes, and safety profile. The composite complete remission rate (CRc) was defined as CR+CRi+CRh at recovery marrow after induction. Primary refractory disease included pts who failed to achieve CR, CRi, or CRh after 2 courses of intensive induction and excluded those who died in aplasia or due to an indeterminate cause. Results: 74 pts with previously untreated AML who received CPX-351 were identified. Median age was 64 years (21-78): 29% of pts were &amp;lt;60 years old, 50% were males, 84% were Non-Hispanic White, 32% had t-AML, 68% had AML-MRC, 20% had prior HMA treatment, and 22% had prior anthracycline exposure. ELN 2022 risk categories were 13% favorable, 20% intermediate, and 68% adverse. 21 pts had complex karyotype (28%), and 16% were TP53 mutant (Table 1). Indications for induction with CPX-351 versus 7+3 included history of prior chemotherapy (n=24), prior MDS (n=32), or MDS-related changes in bone marrow morphology (n=50). The CRc for the total study population was 61% (45/74). Of these, 29% (13/45) achieved MRD negativity by multiparameter flow cytometry &amp;lt;10 -4. CRc in the ELN adverse risk group was 54% (27/50), 73% (11/15) in the intermediate-risk group, and 78% (7/9) in the favorable risk group. Among TP53 mutant pts, CRc was 42% (5/12). CRc in the t-AML group was 71% (17/24), 56% (28/50) in the AML-MRC group, and 53% (8/15) in the prior HMA treatment group. The CRc in pts ≥60 was 63%, 15% were primary refractory, and 37% underwent alloSCT in CR1. In pts &amp;lt;60, the CRc was 54%, 32% were primary refractory, and 27% underwent an alloSCT in CR1 (Table 2). A second course of induction therapy was given for persistent disease at day 14 or similar time point in 36% (n=27) of pts. Among those, 55% (15/27) had primary refractory disease, 20% of the cohort. At a median follow-up of 11 mos, the mOS was 10.8 mos (0.4-54). The mOS for t-AML was 13 mos, whereas the mOS for the group with prior HMA treatment was 10.4 mos. For pts that achieved CR, mOS was 13.6 mos; for pts that achieved MRD negativity, mOS was 13.8 mos. The mOS for pts &amp;lt;60 was 16 mos, and for pts ≥60 was 10 mos (p=0.39). The mOS for pts that achieved CRc in the group &amp;lt;60 was 20.3mos, and for ≥60 was 11.2 mos (p=0.27). Pts that underwent alloSCT in CR1 &amp;lt;60 had mOS of 25 mos; for ≥60, it was 14.2 mos (p=0.37). During induction hospitalization, febrile neutropenia was the most common adverse event in 84% (n=62). ICU treatment was required in 14% (N=5). There were 2 deaths during induction: one due to respiratory failure and one attributed to sepsis. Conclusion: The use of CPX-351 demonstrated efficacy across subgroups, especially in t-AML and pts without prior HMA exposure, as shown in larger studies. In pts &amp;lt;60 years, even though CRc rates were lower, CPX-351 led to longer mOS in those who achieved CRc and in those who underwent alloSCT compared to pts ≥60 years, although it didn't reach statistical significance in this small cohort. Induction therapy outcomes and treatment-related complications in our study corroborate the data for prior CPX-351 studies.

Encouraging Outcome of AML with t(8;16) Following Allogeneic Stem Cell Transplantation in First Remission - a Retrospective Analysis on Behalf of the Acute Leukemia Working Party of the EBMT

In the 2022 European Leukemia Net (ELN) risk classification, acute myeloid leukemia (AML) with translocation t(8;16) was newly classified as AML defined by specific cytogenetic abnormalities, associated with unfavorable prognosis. Translocation (8;16)(p11;p13) is a rare abnormality in AML with female preponderance and occurs more frequently in secondary AML (sAML), especially therapy-related, than in de novo disease. Clinically, AML with t(8;16) is associated with high risk of bleeding, occurrence of extramedullary manifestations, myelomonocytic differentiation, and signs of hemophagocytosis in the bone marrow. The translocation leads to the fusion of acetyltransferase KAT6A (also known as MOZ or MYST3) and CREB binding protein ( CREBBP) genes, both of them involved in hematopoiesis. ELN risk stratification of AML with t(8;16) was based on studies that included relatively low numbers of patients receiving allogeneic stem cell transplantation (alloSCT). In the largest report by Kayser et al. ( Br J Haematol 2021) 21 patients (15 transplanted in first complete remission [CR1], median follow-up 5.5 years) were analyzed. A 5-year overall survival (OS) of 38% was achieved after alloSCT compared to 11% in patients who received chemotherapy only. The aim of our study was to evaluate the outcome of patients with AML harboring t(8;16) after alloSCT in a larger cohort from the EBMT registry. All types of donor, conditioning regimen and graft were included. Sixty patients were identified, of whom 44 had been transplanted in CR1. Median follow-up from alloSCT was 72.3 months, median age was 46.3 years, and 73.3% were female. Karnofsky performance status was &amp;gt;80% in 59 patients, one had missing data. At 2 years after alloSCT, OS and leukemia free survival (LFS) of the entire cohort were 42.7% and 42.2%, respectively, (28.6% and 14.3% in patients transplanted in advanced disease). Cumulative incidence of relapse (RI) and non-relapse mortality (NRM) at two years was 36.9% and 15.3%, respectively, in patients transplanted in CR1, and 78.6% and 7.1%, respectively, in patients transplanted in advanced disease. The 44 patients transplanted in CR1 were analyzed in detail. Basic characteristics were comparable to the entire cohort as described above. Twenty-two of the patients had de novo, 22 had sAML. According to the ELN 2017 classification (not yet including t(8;16) as a factor for poor prognosis), 54.5% had an intermediate and 45.5% an adverse cytogenetic risk. Furthermore, 38.8% had a complex karyotype. Donors were matched related in 34%, matched unrelated in 54%, haploidentical in 5% and cord blood in 7%. Conditioning was myeloablative in 52.3%, whereas 47.7% had received reduced intensity conditioning. Among patients transplanted in CR1, 2- and 5-year OS from alloSCT was 48% and 39.9%, the respective LFS was 46.8% and 35.5%. On multivariate analysis (MVA), harboring t(8;16) within a complex karyotype was the major risk factor for outcome, being associated with higher RI (hazard ratio [HR] 3.38, p=0.01), lower LFS (HR 4.17, p=0.016), and lower OS (HR 3.08, p=0.017). In contrast, patients with t(8;16) outside of a complex karyotype achieved excellent results (Figure 1). Besides a complex karyotype, MVA revealed sAML as an additional, independent risk factor with a higher RI (HR 3.73, p=0.026). Age was the major factor for NRM, reaching 5% vs. 26.5% in patients below or above the median (p=0.02). In conclusion, according to the largest series analyzed in this setting so far, overall results after alloSCT in AML with t(8;16) transplanted in CR1 were favorable, especially in patients without multiple additional cytogenetic abnormalities, achieving a low risk of relapse and a 5-year OS &amp;gt;60%. Hence, alloSCT in CR1 appears to abrogate the unfavorable prognostic value of this translocation. Whether or not t(8;16) does have any additional influence on the outcome of patients with a complex karyotype remains to be evaluated. Figure Legend Figure 1: Outcome of AML with t(8;16) with and without complex karyotype

Outcome of Risk- and Response-Adapted Post-Remission Therapy in Patients with NPM1 AML Treated Intensively

Introduction: Molecular assessment of measurable residual disease (MRD) is a powerful prognostic tool to identify high risk of relapse. Specifically, large studies have shown that MRD negativity of NPM1 after two cycles of intensive chemotherapy (IC) predicts long term remission. The translation of MRD results to treatment decisions such as treatment augmentation (MRD erasing) and referral to an allogeneic stem cell transplant (allo-SCT) is still lacking. The purpose of this study is to report the outcome of AML patients with NPM1 mutation who received IC and achieved remission, in whom NPM1 MRD post cycle 2 of IC, combined with FLT3-ITD status, were used systematically to decide whether patients were to complete intensive consolidations or refer to alloSCT. Methods: This is a retrospective analysis from 3 large hospitals in Israel. Patients were treated with 7+3 for induction and a repeat induction based on day 14 marrow. Midostaurin was added for FLT3mut leukemia since 2018. Consolidation consisted of 3-4 HiDAC cycles at doses of 1-3 g/msqrX6. Gemtuzumab ozogamicin and maintenance with FLT3 inhibitors or CC486 could be added. NPM1 transcript levels (normalized to ABL copies) were collected at diagnosis, after 2 cycles of IC, at the end of IC cycles and during follow-up. Patients were transplanted if a donor was available and any of the following: NPM1 transcript level was not reduced by 3 logs by the end of second cycle chemotherapy, absolute level was &amp;gt;1%, poor risk AML (ELN 2017 guidelines) or high AR FLT3-ITD mutation was present. Patients were followed for relapse (type and timing) and whether a second remission was achieved, as well as for EFS and overall survival. Results: A database search yielded 90 patients with NPM1 AML who were treated according the abovementioned protocol between 5/2015 and 11/2022 and achieved remission, with a median follow-up of 872 days (range 103-2751). Forty-seven patients were to receive consolidation cycles without transplantation in CR1, based on the aforementioned criteria. All but one patient (death from sepsis) completed treatment cycles. During follow-up, 21 (45%) patients relapsed at a median of 343 days. Two patients died while in CR1 during follow-up (extensive burns; sudden death at home). In a subgroup analysis of patients &amp;lt;60y (N=28), there were 11 events (9 relapses and 2 deaths), whereas in patients &amp;gt;60y (N=19) there were 13 events (12 relapses and 1 death during follow-up). Of note, 4 patients &amp;gt;60y were treated with CC486, of whom only 1 relapsed. Of the 18 patients who relapsed and received further treatment (3 had palliative care only), only 1 patient did not enter CR2 (died during salvage). The other 17 patients entered CR2 after salvage regimen (N=7, 4 were qPCR MRDneg, 5 were subsequently transplanted in CR2) or after upfront alloSCT without any salvage regimen (N=10, 4 were qPCR MRDneg). Forty-three patients were planned for alloSCT at CR1 (27 - inadequate molecular response, 16 - ELN risk group). Only one of these patients failed to undergo alloSCT in CR1 as she relapsed. The other 42 patients underwent alloSCT at CR1. In this group of patients, the median progression-free survival was 5 years, with no difference in patients above or below the age of 60. One half of the events (9/18) were relapses and the other half were deaths in remission, almost all were GVHD associated (figure1). Discussion: NPM1 mut AML without FLT3 is still considered by the ELN to have favorable outcome and most patients are not being transplanted at CR1. Yet, many relapse. This study evaluated the outcome of AML patients according to molecular risk stratification and alloSCT consideration by the end of cycle 2 of IC. In line with previous publications, younger patients with standard-risk AML and with adequate molecular response had a favorable outcome, with &amp;gt;60% of them having a disease-free long-term survival without transplantation. Moreover, even in a case of relapse, patients can achieve CR2 with MRDneg and attain long-term remission (90% OS in long-term follow-up). Older patients have a less favorable outcome even when they achieve adequate molecular response with two thirds of them experiencing relapse. Hence, the potential long-term outcome without transplantation needs to be balanced by the high risk of relapse. Nevertheless, even these patients can be successfully treated with either a salvage regimen or immediate transplantation, and &amp;gt;40% of them can be long-term survivors.

The Benefit of Allogeneic Transplant in 1 st Complete Remission in NPM1 Mutated AML with or without FLT3 ITD Is Restricted to Those Testing MRD Positive after Induction - an Analysis of the UK NCRI AML17 and AML19 Studies

Background While there is accumulating evidence that measurable residual disease (MRD) negative patients with intermediate risk AML may not benefit from allogeneic transplantation in 1 st complete remission (CR1-allo), many consider the presence of a FLT3 Internal Tandem Duplication (ITD) an indication for this procedure. However, the studies supporting this practice were mainly performed before the development of sensitive molecular MRD techniques (Schlenk NEJM 2008).The UK NCRI AML17 and AML19 trials studied, then incorporated, MRD by RT-qPCR into the management of patients with NPM1 mutated AML. Methods NCRI AML17 (April 2009 to December 2014) and AML19 (November 2015 to November 2020) were sequential prospective randomised trials for younger adults (18 - 60 years) with newly diagnosed AML. In AML17, decisions regarding CR1-allo were made using a validated risk score incorporating baseline factors and response to induction. In AML19, for patients with NPM1 mutated AML ( NPM1mut) the protocol recommended CR1-allo only in patients testing MRD positive in the peripheral blood (PB) post cycle 2 (PC2), regardless of other baseline risk factors such as FLT3 ITD, based on findings from AML17 (Ivey et al, NEJM 2016). Both trials were performed prior to the availability of midostaurin and FLT3 ITD MRD assays. Here we compare the outcomes of patients with NPM1mut in these trials and assess the benefit of CR1-allo according to FLT3 ITD and molecular MRD status. Time-to-event variables are analysed using the Kaplan-Meier method, and the impact of alloSCT assessed using time-dependent Cox regression and visualised with Simon-Makuch plots. Molecular relapses were included as relapse events, and alloSCT performed after molecular relapse was not considered as CR1. Results 737 patients with NPM1mutAML who achieved CR/CRi and had a valid PC2 PB MRD result were included in the analysis. 60/348 (17%) patients from AML17 and 83/389 (21%) from AML19 tested PB PC2 MRD positive. Overall, CR1-allo was performed in 20% of patients in AML17 and 25% in AML19. Of the MRD positive patients CR1-allo was performed in 16/60 (27%) in AML17 compared to 50/83 (60%) in AML19 where these patients were recommended for transplant. CR1-allo was performed in 18% and 16% of MRD negative patients in AML17 and AML19 respectively. In AML17, as previously reported (Ivey et al, NEJM 2016), patients who were MRD+ had poor outcomes, with 3-year cumulative incidence of relapse (CIR) of 84% and overall survival (OS) of 25%. These outcomes were improved in AML19, with 3y CIR 50% and 3y OS 51%. Across both trials, CR1-allo was associated with a significant survival benefit in MRD+ patients (3y OS 61% vs 24%, HR 0.42, 95%CI 0.26-0.69, p&amp;lt;0.001, Figure A). Patients who were MRD negative had excellent outcomes in both trials (3y CIR 33% and 24% and 3y OS 75% and 83% for AML17 and AML19 respectively). AlloSCT in CR1 provided no survival advantage for MRD- patients (HR 0.83, 95%CI 0.51-1.34, p=0.4). There were a total of 286 patients with NPM1mutFLT3 ITD mut AML with a PC2 PB MRD result across both trials. 81/286 (28%) were PB PC2 MRD+ of whom 32/81 (40%) received CR1-allo (28% in AML17 and 49% in AML19). Outcomes in these high-risk patients were improved in AML19, with 3y CIR 91% vs 68% and 3y OS 22% and 31% for AML17 and AML19 respectively. Those who received CR1-allo had improved outcomes (3y OS 45% vs 18%, HR 0.52, 95% CI 0.29-0.93, p=0.03) consistent with the overall MRD+ population. In the 70% of NPM1mutFLT3 ITD mut AML patients who achieved PB PC2 MRD-, outcomes were encouraging in both AML17 (3y CIR 37%, 3y OS 75%) and AML19 (3y CIR 27%, 3y OS 80%). CR1-allo was performed in 20% (19% in AML17, 21% in AML19), with no survival benefit for transplant (HR 0.80, 95% CI 0.37-1.72, p=0.6, Figure B). There remained no benefit when restricted to those with high (&amp;gt;0.5) FLT3 ITD allelic ratio (HR 0.63, 95% CI 0.2 - 2.23, p = 0.50) and there was also no evidence of an interaction between allelic ratio and benefit from transplant for MRD negative patients (p=0.86). Conclusion Molecular MRD can be used to stratify decision making concerning post remission therapy in patients with NPM1mut AML. Patients who achieve MRD negativity in the peripheral blood by the end of course 2 are at low risk of relapse and we found no evidence of benefit from allogeneic transplant in CR1, including in the subset with FLT3 ITD. This finding contrasts with MRD+ patients where there was a significant survival benefit for CR1 transplant.

Early T-Cell Precursor Leukemia: A High-Risk Subtype of Acute Lymphoblastic Leukemia, Single Center Experience in Jordan

Background and ObjectivesEarly T-cell precursor (ETP) acute lymphoblastic leukemia/lymphoma (ALL/LBL) is a newly recognized entity of T-lymphoblastic leukemia/lymphoma. The optimal therapeutic approaches to adult patients are poorly studied. Patients and MethodsWe compared the outcomes of adult's patents with ETP-ALL/LBL who received frontline chemotherapy regimens with other T-ALL/LBL immunophenotypic subtypes. Patients with ETP-ALL/LBL were identified based on CD1a (-), CD8 (-), CD5 (-) (dim), and positivity for 1 or more stem cell or myeloid antigens. ResultsSixty-nine patients were included between the years 2010 and 2021 (19 ETP-T-ALL/LBL; 50 non ETP- T-cell ALL/LBL). The median age was 26 year (IQR: 21, 33). Fifty-six patients presented as ALL, while 16 with lymphoblastic lymphoma. Forty-seven patients achieved complete remission, and 43 were alive at last encounter. The complete remission rate in patients with ETP-ALL/LBL was lower than that of non-ETP-ALL/LBL patients (32% vs. 68%; P = .2), and the MRD at end of induction was significantly higher (26% vs. 6.2%, P < .001), and more likely to receive allo-SCT consolidation in CR1 (95% vs. 40%, P < .001). After a median follow-up of survivors of 48 months (range: 32-74 months), the median overall survival for patients with ETP-ALL/LBL was not reached versus 11.5 months for the non-ETP-ALL/LBL patients (P = .014)). Twenty-six patients receive allo-SCT in CR1. There was no significant difference in overall survival (79% vs. 70%; P = .49) between both transplant-cohorts in both groups. ConclusionETP-ALL/LBL represents a high-risk disease subtype of adult ALL. Novel treatment strategies are needed to improve treatment outcomes in this patient's population

Measurable Residual Disease and Fusion Partner Independently Predict Survival and Relapse Risk in Childhood KMT2A-Rearranged Acute Myeloid Leukemia: A Study by the International Berlin-Frankfurt-Münster Study Group.

A previous study by the International Berlin-Frankfurt-Münster Study Group (I-BFM-SG) on childhood KMT2A-rearranged (KMT2A-r) AML demonstrated the prognostic value of the fusion partner. This I-BFM-SG study investigated the value of flow cytometry-based measurable residual disease (flow-MRD) and evaluated the benefit of allogeneic stem-cell transplantation (allo-SCT) in first complete remission (CR1) in this disease. A total of 1,130 children with KMT2A-r AML, diagnosed between January 2005 and December 2016, were assigned to high-risk (n = 402; 35.6%) or non-high-risk (n = 728; 64.4%) fusion partner-based groups. Flow-MRD levels at both end of induction 1 (EOI1) and 2 (EOI2) were available for 456 patients and were considered negative (<0.1%) or positive (≥0.1%). End points were 5-year event-free survival (EFS), cumulative incidence of relapse (CIR), and overall survival (OS). The high-risk group had inferior EFS (30.3% high risk v 54.0% non-high risk; P < .0001), CIR (59.7% v 35.2%; P < .0001), and OS (49.2% v 70.5%; P < .0001). EOI2 MRD negativity was associated with superior EFS (n = 413; 47.6% MRD negativity v n = 43; 16.3% MRD positivity; P < .0001) and OS (n = 413; 66.0% v n = 43; 27.9%; P < .0001), and showed a trend toward lower CIR (n = 392; 46.1% v n = 26; 65.4%; P = .016). Similar results were obtained for patients with EOI2 MRD negativity within both risk groups, except that within the non-high-risk group, CIR was comparable with that of patients with EOI2 MRD positivity. Allo-SCT in CR1 only reduced CIR (hazard ratio, 0.5 [95% CI, 0.4 to 0.8]; P = .00096) within the high-risk group but did not improve OS. In multivariable analyses, EOI2 MRD positivity and high-risk group were independently associated with inferior EFS, CIR, and OS. EOI2 flow-MRD is an independent prognostic factor and should be included as risk stratification factor in childhood KMT2A-r AML. Treatment approaches other than allo-SCT in CR1 are needed to improve prognosis.

Extramedullary Involvement of Acute Myeloid Leukaemia: A Single Centre Experience on the Influence of Pre and Post Transplant Extramedullary Disease on Outcomes for Patients Undergoing Allogeneic Stem Cell Transplantation

Introduction: Extramedullary presentation of acute myeloid leukaemia (EM-AML) is rare, occurring in 2.5 -9.1% of patients. There is limited evidence on how to manage these patients specifically, with its impact on outcomes for patients undergoing allogeneic haematopoietic stem cell transplant (AlloSCT) not well characterised (Bakst et al. Blood 2011). Methods: A single centre retrospective analysis was conducted for patients diagnosed with EM-AML pre- or post-AlloSCT between August 2000 and June 2021 to characterise outcomes for this patient group. Results: 29 patients with AML (male = 18, female =11) were identified from the institutional alloSCT database. Median age at AlloSCT was 43 years (range 17-68). 76% (n=22) presented with EM-AML pre- and 24% (n=7) post-AlloSCT. 62% (n=18) had EM-AML and bone marrow involvement against 38% (n=11) with isolated EM-AML. The most common site of involvement was skin (52%; n=14). 7 patients had a FLT3 mutation and 3 had a complex karyotype at diagnosis. 55% (n=16) of patients underwent AlloSCT in CR1, 21% (n=6) in CR2, 3% (n=1) in CR3, 14% (n=4) in relapse. Remission status for one patient was not recorded and one was untreated pre-AlloSCT. 66% (n=19) underwent myeloablative conditioning and 41% (n=10) reduced intensity conditioning. Donor type included matched sibling donor (48%; n=14), matched Unrelated Donor (34%; n=10), Haplo-identical donor (14%; n=4) and umbilical cord (2%; n=1). 52% (n=15) experienced acute graft-versus-host disease (GvHD) and 62% chronic GvHD (n=18). Median overall survival (OS) post AlloSCT was 24 months (Range 1-120). Median OS for patients in CR1 pre-AlloSCT was 28 months vs 53 months for patients in CR2. The most common cause of death was progressive disease (36%). Median Relapse Free survival (RFS) post AlloSCT was 15 months (Range 1-116). Of the 7 patients who relapsed with EM-AML post AlloSCT only 1 remains alive at 49 months. Conclusion: Our retrospective series confirms the poor outcomes associated with EM-AML despite AlloSCT with a median OS of 24 months. Additionally, patients who relapse post-allograft with EM-AML have an abysmal outcome with the majority dying of progressive disease. New treatment strategies are therefore needed to improve outcomes in this difficult patient group. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Tandem Duplications of the UBTF gene in Adult AML: A Rare but Recurrent Alteration Associated with Myelodysplasia and Poor Outcome

The upstream binding transcription factor (UBTF) is a nucleolar protein that regulates the transcription of ribosomal genes as a component of the RNA Pol I pre-initiation complex. Recently, tandem duplication mutations of the UBTF gene (UBTF-TDs) were identified as recurrent alterations in pediatric AML (Umeda et al., 2022), potentially representing a new subtype-defining lesion. UBTF-TDs were found to be associated with normal karyotype (NK) or trisomy 8 (+8), FLT3-ITD and WT1 mutations as well as poor prognosis. Data on the role of UBTF-TD in adult AML are limited. In the present study, we therefore analyzed the prevalence and prognostic significance of UBTF-TDs in a large cohort of adult AML patients (pts). Methods: Pts included were registered and treated in clinical protocols of the Study Alliance Leukemia (SAL) (AML96, AML2003, AML60+, SORAML) or the SAL-registry. Screening for UBTF-TDs was done by PCR covering exon 13 of the UBTF gene with 6-FAM labelled primers followed by high-resolution fragment analysis using genomic DNA isolated at diagnosis. Mutations were confirmed by Sanger sequencing. All UBTF mutant samples were further analyzed by targeted next generation sequencing (Archer Myeloid Panel) for the presence of co-occurring alterations. Results: Somatic mutations in UBTF were identified in 52 (1.2%) of 4247 pts. Mutations varied in size (3 to 309 bps), all yielding in-frame insertions, duplications or deletions in exon 13 of the UBTF gene. UBTF-TD AMLs frequently presented with a normal karyotype (46%) or +8 (36.5%). Similar to findings in pediatric pts, the co-mutation profile showed significant differences between UBTF-mut and UBTF-wt pts, i.e. UBTF-TDs were significantly associated with FLT3-ITD (48%, p<.001) or WT1 mutations (52%, p<.001), while DTA co-mutations were exceedingly rare (DNMT3A 1.9%; TET2 3.8%; ASXL1 3.8%) (Fig. 1A). Furthermore, UBTF-TDs and several class-defining lesions, i.e. reciprocal translocations such as RUNX1::RUNX1T1,DEK::NUP214 or mutations in CEBPA or NPM1 were mutually exclusive. The prevalence of UBTF-TDs showed a strong negative correlation with increasing age, ranging from 10% in patients <20 years (yrs) to 0.05% in patients >70 yrs, respectively. Accordingly, pts with UBTF-TDs were significantly younger (median age 41 yrs; range 17-77 yrs) than wt pts (med. 57 yrs; range 15-90 yrs, p<.001). Association with clinical parameters revealed significantly lower hemoglobin levels and platelet counts at diagnosis for UBTF-mut pts compared to UBTF-wt pts (median Hb 8.7 vs. 9.2 g/dL; p=.02; median PLT 31.5 vs 53 x 109/L; p=.003). Although UBTF-TDs mainly affected younger pts, cytomorphologic assessment revealed a clear association with myelodysplastic changes in about 60% of patients. Univariate analysis showed a significantly higher rate of complete remissions (CR) in UBTF-mut pts (92.3%) compared to UBTF-wt pts (70.8%) (p<.001). However, UBTF-mut pts had shorter overall (OS) and event-free survival (EFS). This effect was particularly pronounced in the subgroup of pts under 60 years of age (median OS 20.4 months in UBTF-mut pts vs. 45.3 months in UBTF-wt pts, p=.079; median EFS 6.7 months in UBTF-mut pts vs. 11 months in UBTF-wt pts, p<.001) (Fig.1B), who represented the majority (45/52, 87%) of UBTF-TD patients, and in patients with co-mutations of the WT1 gene (data not shown). AlloSCT performed in CR1 in 11 pts (21%) did not improve outcome. In multivariable analyses, the presence of UBTF-TD was associated with a trend for shorter OS (HR: 1.39; 95% CI 0.98-2, p=.06) and significantly worse EFS (HR: 1.68; 95% CI 1.24-2.3; p<.001). Conclusions: This analysis of a large cohort of adult patients with newly diagnosed AML revealed that UBTFmutations can be found in about 1% of all patients with AML, but are considerably more common in young adults. As in pediatric patients, they are associated with a specific cytogenetic and molecular profile, i.e. high rate of +8, FLT3-ITD and WT1 mutations. As a novel finding, adult UBTF-TD patients frequently showed signs of myelodysplasia. The distinct molecular genotype and the fact that UBTF-TDs were associated with a dismal outcome, even in patients treated with alloSCT in CR1, support the classification of this group as a new disease entity and indicate that novel treatment strategies are needed in this subgroup of patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Long-term outcomes of newly diagnosed CRLF2 rearranged B-cell ALL.

7040 Background: CRLF2 rearranged B-ALL, a subtype of Ph-like ALL, constitutes a high-risk subset of B-ALL with poor outcomes with chemotherapy. Targeted therapies such as blinatumomab (blina) or inotuzumab (ino) may improve treatment outcomes for these patients (pts). Methods: We retrospectively analyzed pts with newly diagnosed B-ALL (diagnosed between 01/2001 and 12/2021) at our center who had documented CRLF2 overexpression. Initial therapy, including use of ino and blina in CR1 were noted. Outcomes measures included CR/CRi, MRD response, RFS and OS. Results: A total of 76 pts with a median age of 38 years (yrs) (range, 18-80) were identified, of which 70% were males and 81% were of Hispanic ethnicity. All pts had overexpression of CRLF2 documented by flow cytometry or gene expression profile. A subset of pts (n=37) had a concomitant CRLF2 FISH performed with all confirming CRLF2 rearrangement. Baseline disease parameters, treatment and outcomes are detailed in Table. Sixty-five pts (85%) received Hyper-CVAD based induction therapy (HCVAD, n=51; mini-HCVD, n=14) and 11 (15%) received augmented BFM. Among the HCVAD/mini-HCVD treated pts, 37% received blina in CR1 during consolidation at a median of 3.6 months after starting induction therapy, 34% received ino in CR1 (most commonly starting in cycle 1 as part of mini-HCVD + ino regimen) and 22% received both ino and blina in CR1. We focus on the outcomes of 65 pts treated with HCVAD/mini-HCVD. The median follow-up was 18 months (mos). CR/CRi rate after C1 among HCVAD/mini-HCVD treated pts was 52/65 (80%) with 25/47 (53%) MRD evaluable pts achieving MRD-neg post C1. The median RFS and OS was 17.6 and 26.6 mos, respectively. CR/CRp rate after C1 among pts who received mini-HCVD + ino in C1 was 100% (14/14) with 79% MRD-neg. On landmark analysis to the time to blina initiation, blina treated pts had similar RFS and trended for improved OS. A total of 19/65 (30%) had allo-SCT in CR1; all were MRD-neg prior to allo-SCT. Landmark analysis for OS based on time to allo-SCT (6 mos) favored SCT in CR1 (47.2 vs. 17.6 mos, p=0.04). Conclusions: Despite improvements in treatment options, CRLF2 overexpressed B-ALL continue to have inferior outcomes. Earlier initiation of targeted therapies might improve outcomes.[Table: see text]

Allogeneic Transplantation in Fit Older Adults Is Feasible and Encouragingly Efficacious. Post Remission Data from the Prospective ECOG-ACRIN (E2906) Clinical Study

Allogeneic Transplantation in Fit Older Adults Is Feasible and Encouragingly Efficacious. Post Remission Data from the Prospective ECOG-ACRIN (E2906) Clinical Study

Outcome of Allogeneic Stem Cell Transplantation in T Cell Lymphoblastic Lymphoma

Background T cell lymphoblastic lymphoma (T-LBL) is an aggressive form of non-Hodgkin lymphoma occurring in predominantly adolescent and young adults.Although T-LBL is achemotherapy-sensitive disease, relapse is common with conventional chemotherapies. Allogeneic stem cell transplantation (allo-SCT) may be effective in patients with high-risk features or relapsed/refractory patients.Objective To investigate the effect of allo-SCT in the treatment of T-LBL.Methods T-LBL patients who received allo-SCT from August 2007 to March 2017 in our center were recruited in this retrospective study.Results (1) 37 T-LBL patients were enrolled in this study, including 25 males and 12 females with a median age of 21 years old (ranged from 8 to 47 years old). A total of 10 (27%) from HLA-matched siblings,24 (65%) patients received grafts from haploidentical family donors, 2 (5%) from matched unrelated donors,and 1(3%) from cord blood. (2) With a median follow up of 20 months (4 - 119 months), 3 year overall survival (OS) ,progression-free survival (PFS) and relapse were 71.7%, 69.5% and 23.6%,respectively. (3) 12/37 patients developed acute graft-versus-host diease (GVHD) ,including 6 (16%) with grade III-IV aGVHD. 8/37 patients developed chronic GVHD. The transplant-related mortality was 13.5%.(4) Allo-SCT in first complete remission (CR1) was associated with improved OS (3-year estimates: 79.1% vs 45.5%, P=0.001) and improved PFS (62.5% vs 39.1%, P=0.001). On multivariable analysis, allo-SCT in CR1 was the factor associated with the prolonged OS (hazard ratio [HR] = 0.095;95% confidence interval [CI] : 0.014-0.655; P=0.017) and PFS (HR=,0.085 95% CI=0.014-0.515; P=0.007).Conclusion Allo-SCT for T-LBL patients revealed a proming outcome. Disease status the only independent factor affecting the OS and PFS, and allo-SCT should be recommended in CR1. DisclosuresNo relevant conflicts of interest to declare.

A Pilot Study of Allogeneic Hematopoietic Stem Cell Transplantation for Intermediated-risk Acute Myeloid Leukemia Patients.

For intermediate risk acute myeloid leukemia patients, allogeneic hematopoietic stem cell transplantation (alloSCT) and chemotherapy are equally recommended as consolidation after first complete remission (CR1). In real-world, alloSCT might not be readily available, but there is paucity of data on the optimal timing of alloSCT for these patients. In this pilot study, we compared the outcomes of 13 patients undergoing alloSCT in CR1 with 13 patients undergoing alloSCT after relapse (non-CR1) to examine whether upfront alloSCT yields a better prognosis. There were no differences between the two groups with regards to relapse-free survival (p=0.507) and overall survival (p=0.798). There were more chronic graft-versus-host-disease (GVHD) in the CR1 group compared to the non-CR group (p=0.001), but no difference in acute GVHD. The outcome of alloSCT after relapse is not inferior to that of alloSCT in CR1, supporting the role of alloSCT after relapse in the setting of limited donors and resources.

Validation of the European Leukemianet 2017 Prognostic Classification for Patients with De Novo Acute Myeloid Leukemia Treated with a Risk-Adapted Protocol (CETLAM 2012)

Introduction The European LeukemiaNet (ELN) 2017 classification for acute myeloid leukemia (AML) stratifies patients in 3 risk categories, according to genetic features of the disease. ELN classification is commonly used to guide post-remission treatment; favorable risk patients do not seem to benefit from allogeneic hematopoietic transplantation (alloHCT) in first complete remission (CR1) while this procedure is highly recommended in adverse risk patients. Post-remission treatment in intermediate risk patient is still debated. This classification has not been prospectively validated. Herein we analyze the prognostic impact of ELN 2017 classification in patients treated with the same protocol (CETLAM-12), including a well-defined preplanned alloSCT policy according to genetic risk. Methods We analyzed characteristics and outcome of patients diagnosed with de novo AML, included in CETLAM-12 protocol for patients up to 70 years, with an available genetic characterization at diagnosis allowing an accurate ELN 2017 stratification. Genetic risk allocation was based on cytogenetic analysis and pre-specified RT-PCR of determined markers (including CBF-rearrangement, NPM1, FLT3, CEBPA, and MLL-PTD) performed in all patients, and targeted Next Generation Sequencing testing (available in 143 patients). CETLAM-12 protocol defines a genetic risk stratification in three groups, closely similar to that proposed by the ELN 2017 classification, and recommends a post-remission strategy based on this risk assessment. Patients from the favorable group received three courses of consolidation with high-dose cytarabine (HiDAC), whereas alloSCT in CR1 is strongly recommended for intermediate and adverse risk patients following one HiDAC-based consolidation course. Results We included in the study 813 patients (400F/413M; median age 56, 17-76); with a 37 months median estimated follow-up (range 0.1-92). The outcomes of the entire cohort are shown in table 1. Out of all patients, 641 could be classified according to the ELN 2017 classification, due to the presence of risk defining genetic features identified by any of described methods. In the group of .atients allocated in the favorable risk category (n=316; 49%), twenty-seven patients died during induction. Fifty-eight relapses were observed, mostly in patients with NPM1 mutation (n=41). AlloSCT was finally performed in CR1 in 84 patients (27%) due to MRD persistence or reappearance (n=40), overt hematological relapse (n=27), persistent aplasia following chemotherapy (n=3) and protocol deviation (n=14). In the group of patients allocated in the intermediate risk category (n=95; 15%), twelve patients died during induction. AlloSCT in CR1 was performed in 62 patients (67%), with 5 patients receiving an alloSCT in CR2. In the group of patients allocated in the adverse risk category (n=230; 36%), twenty-five patients died during induction. AlloSCT could be finally performed in CR1 in 138 patients (60%) and 88 relapses occurred (42 before alloSCT, 46 after alloSCT). Amongst ELN adverse risk patients, a subgroup with a significant worse outcome has been identified, defined by AML with complex karyotype +/- TP53 mutation or chromosome 3q26/MECOM-GATA2 rearrangement. This group (ELNadv+) presented a lower CR rate, with a higher relapse rate and fewer proportion of patients who receive a pre-planned alloSCT in CR1. OS and EFS of ELNadv+ is significantly lower than ELN adverse patients. In the multivariate analysis for OS including age, sex, WBC count at diagnosis and number of cycles to achieve CR, only age and ELNadv+ status showed independent prognostic value. Outcome data is summarized in table and figures attached. Conclusions The initial risk-adapted post-remission assignment planned in CETLAM-12 could be performed in the majority of patients. Despite this different proposed post-remission treatment, ELN risk classification was able to identify three groups of patients with a markedly different outcome. Interestingly, within the unfavorable ELN category, a very high-risk ELNadv+ subgroup can be distinguished, with a dismal outcome with current approach, warranting the implementation of innovative pre and post-transplant strategies aimed to prevent treatment failure. Figure Disclosures Tormo: MSD: Honoraria; Janssen: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Honoraria; Servier: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. Salamero:Pfizer: Consultancy; Jazz Pharmaceuticals: Consultancy, Honoraria; Daichii Sankyo: Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Sierra:Jazz Pharmaceuticals: Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead-Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Outcome of Patients with T-Cell Acute Lymphoblastic Leukemia/Lymphoma with Early T-Cell Precursor-like Immunophenotype with Strong CD5 Expression

Outcome of Patients with T-Cell Acute Lymphoblastic Leukemia/Lymphoma with Early T-Cell Precursor-like Immunophenotype with Strong CD5 Expression

Midostaurin in combination with chemotherapy is most effective in patients with acute myeloid leukemia presenting with high FLT3‐ITD allelic ratio who proceed to allogeneic stem cell transplantation while in first complete remission

Midostaurin, a multikinase and FLT3 inhibitor, is the first non-chemotherapy agent approved and widely adopted for the treatment of FLT3-ITD acute myeloid leukemia (AML). Yet, its role in improving survival of patients referred to allogeneic stem cell transplantation (allo-SCT) in first complete remission (CR1) needs to be defined. This multicenter study retrospectively evaluated the outcome of 119 FLT3-ITD AML patients [59 (49.6%) males and 60 females] intensively treated between 2015 and 2019 at five Israeli centers. In our cohort, allo-SCT in CR1 was widely implemented (47%) and patient stratification was based on the current allelic ratio (AR) cutoff of 0.5. Ninety-eight patients (82.3%) achieved CR1/CR with incomplete count recovery (CRi). Death during induction was reported in 7 (5.9%) patients. In multivariate analysis, midostaurin use and allo-SCT in CR1 were the most significant factors affecting overall survival (OS). Midostaurin incorporation in chemotherapy regimens significantly improved CR+CRi rates (P=.002), reduced relapse rates (P=.02), and was remarkably advantageous for high-AR patients (2-year OS 82%). In low-AR patients, the midostaurin effect was much less prominent. Our results demonstrate benefits of midostaurin incorporation in intensive chemotherapy regimens, particularly for high-AR AML patients to whom it should be offered along with allo-SCT in CR1.

Comparison of Early T-Cell Precursor and Non-ETP Subtypes Among 122 Chinese Adults With Acute Lymphoblastic Leukemia

Background: Adult T-cell acute lymphoblastic leukemia (T-ALL) is a rare hematological malignancy and significantly linked to poor outcomes. Early T-cell precursor (ETP) leukemia is a unique subtype of T-ALL. The aim of this study is to compare the differences between ETP and non-ETP ALLs in China.Methods: We retrospectively analyzed the records of 122 adult T-ALL patients diagnosed and treated at our center between January 2014 and June 2019. All the patients enrolled were categorized into ETP and non-ETP ALL by immunophenotype, and further statistical analyses about clinical data and prognostic factors were performed.Results: Among the 122 cases, the male-to-female ratio was 2.8:1, and the median age is 29 (range, 16–82) years. Except for 10 patients with insufficient immunophenotyping results, 47.3% (53/112) are ETP and 52.7% (59/112) are non-ETP. Compared with non-ETP patients, ETP-ALL patients had lower white blood cell counts and lactate dehydrogenase levels, while they were older and had higher platelet counts and fibrinogen levels (all p < 0.05). Complete remission (CR) was achieved in 68.0% (83/122) of patients, 64.2 and 76.3% in ETP and non-ETP, respectively (p = 0.160). In total, 44.6% (37/83) of patients relapsed. Allogeneic stem cell transplantation (allo-SCT) was successfully performed in 36.1% (44/122) of patients, of which 79.5% (35/44) were in CR1. With a median follow-up of 9.1 (range, 0.5–70.3) months, the estimated 2-year overall survival (OS) and relapse-free survival (RFS) rates for the cohort were 38.0 ± 5.1 and 39.1 ± 6.3%, respectively. In the ETP group, the 2-year OS rate was 40.7 ± 8.2% and the RFS rate was 47.2 ± 10.7%, while in the non-ETP group, the 2-year OS rate was 37.9 ± 7.0% and the RFS rate was 39.2 ± 8.3% (both p > 0.05). In the landmark analysis of CR1 patients who had a survival of more than 6 months, the allo-SCT group had significantly better survival outcomes than the chemotherapy group, and the 2-year OS rates and RFS rates were 80.1 ± 7.3 vs. 28.4 ± 8.4% and 68.9 ± 8.8 vs. 12.8 ± 7.2%, respectively (both p < 0.0001). A multivariate analysis suggests that allo-SCT acts as an independent prognostic factor for both OS and RFS.Conclusions: Our results revealed that ETP accounted for a high proportion of T-ALL in Chinese. There are no CR rates and prognosis differences between ETP and non-ETP. Allo-SCT in CR1 can significantly improve patients' survival.

Inferior outcome of allogeneic stem cell transplantation for secondary acute myeloid leukemia in first complete remission as compared to de novo acute myeloid leukemia

Following chemotherapy, secondary acute myeloid leukemia (sAML), occurring after antecedent hematologic diseases, previous chemotherapy or radiation, has an inferior prognosis compared with de novo AML. To define the outcome of sAML in the context of allogeneic stem cell transplantation (alloSCT), a retrospective, registry-based comparison was performed, including 11,439 patients with de novo and 1325 with sAML. Among transplants in first complete remission (CR1) (n = 8,600), the 3-year cumulative incidence of relapse (RI) and non-relapse mortality (NRM) was 28.5% and 16.4% for de novo, and 35% and 23.4% for sAML. Three-year overall survival (OS), leukemia-free survival (LFS) and Graft-versus-Host Disease/relapse-free survival (GRFS) was 60.8%, 55.1%, and 38.6% for de novo, and 46.7%, 41.6%, and 28.4% for sAML, respectively. In multivariate analysis, sAML was associated with a lower OS (HR = 1.33 [95% CI = 1.21–1.48]; p < 10−5), LFS (HR = 1.32 [95% CI = 1.19–1.45]; p < 10−5) and GRFS (HR = 1.2 [95% CI = 1.1–1.31]; p < 10−4) and higher NRM (HR = 1.37 [95% CI = 1.17–1.59]; p < 10−4) and RI (HR = 1.27 [95% CI = 1.12–1.44]; p < 10−3). Results of the Cox model were confirmed in a matched-pair analysis. In contrast, results did not differ between de novo and sAML after alloSCT in induction failure or relapse. Hence, this analysis identified sAML as an independent risk factor for outcome after alloSCT in CR1.

Allogeneic stem cell transplantation in AML with t(6;9)(p23;q34);DEK-NUP214 shows a favourable outcome when performed in first complete remission.

Acute myeloid leukaemia (AML) with t(6;9)(p23;q34) is a poor-risk entity, commonly associated with FLT3-ITD (internal tandem duplication). Allogeneic stem-cell tranplantation (allo-SCT) is recommended, although studies analysing the outcome of allo-SCT in this setting are lacking. We selected 195 patients with t(6;9) AML, who received a first allo-SCT between 2000 and 2016 from the EBMT (European Society for Blood and Marrow Transplantation) registry. Disease status at time of allo-SCT was the strongest independent prognostic factor, with a two-year leukaemia-free survival and relapse incidence of 57% and 19% in patients in CR1 (first complete remission), 34% and 33% in CR2 (second complete remission), and 24% and 49% in patients not in remission, respectively (P<0·001). This study, which represents the largest one available in t(6;9) AML, supports the recommendation to submit these patients to allo-SCT in CR1.