Allogeneic hematopoietic cell transplantation for acute myeloid leukemia with hyperdiploid complex karyotype.

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the best consolidation strategy for acute myeloid leukemia (AML) with complex karyotype (CK). However, CK is a heterogenous and highly diverse entity. Numerical abnormalities have been associated with a controversial prognosis and AML with only multiple numerical abnormalities known as pure hyperdiploid karyotype (HDK) may have a distinct prognosis after allo-HCT compared to non-pure HDK CK AML. A total of 236 patients were identified within the EBMT registry as having HDK comprising 95 pure (pHDK) and 141 with other cytogenetic abnormalities (HDK+). The 2-year probability of leukemia-free survival (LFS) was 50% for pHDK and 31% for HDK+ (p = 0.003). The 2-year probability of overall survival (OS) was 57% for pHDK and 36% for HDK+ (p = 0.007). The 2-year cumulative incidence of relapse (RI) was 22% for pHDK and 44% for HDK+ (p = 0.001). The 2-year probability of graft-versus-host disease (GvHD)-free and relapse-free survival (GRFS) was 36% for pHDK and 21% for HDK+ (p = 0.01). On multivariate analysis, pHDK remained associated with significantly better LFS, OS and GRFS and lower RI (all p-values <0.004). pHDK AML constitutes probably a distinct cytogenetic entity from HDK+ or other non-hyperdiploid CK AML with better outcomes after allo-HCT.

Organ complications after CD19 CAR T-cell therapy for large B cell lymphoma: a retrospective study from the EBMT transplant complications and lymphoma working party.

We investigated ≥ grade 3 (CTC-AE) organ toxicities for commercial CD19 chimeric antigen receptor T cell (CAR-T cell) products in 492 patients (Axi-Cel; n = 315; Tisa-Cel; n = 177) with Large B-cell Lymphoma in the European Society for Blood and Marrow Transplantation (EBMT) CAR-T registry. The incidence of ≥ grade 3 organ toxicities during the first 100 days after CAR-T was low and the most frequent were: renal (3.0%), cardiac (2.3%), gastro-intestinal (2.3%) and hepatic (1.8%). The majority occurred within three weeks after CAR-T cell therapy. Overall survival was 83.1% [79.8-86.5; 95% CI] at 3 months and 53.5% [49-58.4; 95% CI] at one year after CAR-T. The most frequent cause of death was tumour progression (85.1%). Non-relapse mortality was 3.1% [2.3-4.1; 95% CI] at 3 months and 5.2% [4.1-6.5; 95% CI] at one year after CAR-T. The most frequent causes of non-relapse mortality were cell-therapy-related toxicities including organ toxicities (6.4% of total deaths) and infections (4.4% of total deaths). Our data demonstrates good safety in the European real-world setting.

Autologous stem cell transplantation in adult patients with intermediate-risk acute myeloid leukemia in first complete remission and no detectable minimal residual disease. A comparative retrospective study with haploidentical transplants of the global committee and the ALWP of the EBMT.

In patients with acute myeloid leukemia (AML) of intermediate-risk (IR) in first remission (CR1) with no measurable residual disease (MRD negative), the choice of the best consolidation is questionable. 1122 adult patients from 196 centers, transplanted in 2010-21 were analyzed: 547 received an autologous stem cell transplantation (ASCT) and 575 a Haploidentical donor transplant. Because of a significant interaction, comparisons were done separately for patients with wild-type FLT3 (FLT3-wt) and FLT3-ITD mutation (FLT3-ITD). In FLT3-wt patients, haploidentical transplants had two year lower relapse incidence (RI) (16.9% versus 32.6%; HR = 0.40, p < 0.001), higher NRM higher (17.2% vs 3.5%; HR = 7.02, p < 0.001), similar LFS (65.9% vs 63.8%; p = 0.37) and lower OS (73.2% vs 80.6%; HR = 1.69, p = 0.018). In FLT3-ITD patients, haploidentical transplants had two year lower RI (8.2% vs 47.8%; HR = 0.14, p < 0.001) higher NRM (20.2% vs 5.6%; HR = 3.43, p = 0.002), better LFS (71.5% vs 46.6%; HR = 0.53, p = 0.007) and similar OS (73.5% vs 61.9%; p = 0.44). In IR AML patients with FLT3-wt in MRD negative CR1, autologous stem cell transplantation is a valid option, while in patients with FLT3-ITD, haploidentical transplant is better. Whether autologous transplantation is superior to chemotherapy in FLT3-wt patients and the role of maintenance therapy with FLT3 inhibitors remain to be studied.

Current incidence, severity, and management of veno-occlusive disease/sinusoidal obstruction syndrome in adult allogeneic HSCT recipients: an EBMT Transplant Complications Working Party study.

The current incidence, diagnostic policy, management, and outcome of VOD/SOS at EBMT centers were studied. All centers that had performed allogeneic HSCTs in adult patients within one defined year were invited to the study. Seventy-one centers participated with a total of 2886 allogeneic transplantations and 93 cases of VOD/SOS in 2018. The cumulative incidence of VOD/SOS at day 21 was 1.8% and at day 100 2.4%. Of 67 cases with detailed data, 52 were classical and 15 (22%) late onset (>day 21). According to the EBMT criteria, 65/67 patients had at least two VOD/SOS risk factors. The severity grades were: mild 0, moderate 3, severe 29, very severe 35. Fifty-four patients were treated with defibrotide. VOD/SOS resolved in 58% of the patients, 3/3 with moderate, 22/28 with severe, and 12/33 with very severe grade (p < 0.001). By day 100, 57% of the patients were alive; 3/3 with moderate, 22/29 with severe, and 13/35 with very severe VOD/SOS (p = 0.002). In conclusion, the incidence of VOD/SOS was low. Severe and very severe grades dominated. Very severe grade predicted poor outcome compared to severe grade further supporting the concept of early diagnosis and treatment to avoid a dismal outcome.

Total body irradiation versus busulfan based intermediate intensity conditioning for stem cell transplantation in ALL patients >45 years-a registry-based study by the Acute Leukemia Working Party of the EBMT.

Allogeneic hematopoietic cell transplantation is a potentially curative treatment in high-risk acute lymphoblastic leukemia (ALL). Conditioning regimens based on ≥12 Gray total body irradiation (TBI) represent the current standard in patients ≤45 years, whereas elderly patients frequently receive intermediate intensity conditioning (IIC) to reduce toxicity. To evaluate the role of TBI as a backbone of IIC in ALL, a retrospective, registry-based study included patients >45 years transplanted from matched donors in first complete remission, who had received either fludarabine/TBI 8 Gy (FluTBI8, n = 262), or the most popular, irradiation-free alternative fludarabine/busulfan, comprising busulfan 6.4 mg/kg (FluBu6.4, n = 188) or 9.6 mg/kg (FluBu9.6, n = 51). At two years, overall survival (OS) was 68.5%, 57%, and 62.2%, leukemia-free survival (LFS) was 58%, 42.7%, and 45%, relapse incidence (RI) was 27.2%, 40%, and 30.9%, and non-relapse-mortality (NRM) was 23.1%, 20.7%, and 26.8% for patients receiving FluTBI8Gy, FluBu6.4, and FluBu9.6, respectively. In multivariate analysis, the risk of NRM, acute and chronic graft-versus-host disease was not influenced by conditioning. However, RI was higher after FluBu6.4 (hazard ratio [HR] [95% CI]: 1.85 [1.16-2.95]), and LFS was lower after both FluBu6.4 (HR: 1.56 [1.09-2.23]) and FluBu9.6 (HR: 1.63 [1.02-2.58]) as compared to FluTBI8. Although only resulting in a non-significant advantage in OS, this observation indicates a stronger anti-leukemic efficacy of TBI-based intermediate intensity conditioning.

Severe cytopenia after CD19 CAR T-cell therapy: a retrospective study from the EBMT Transplant Complications Working Party.

We investigated the incidence and outcome of anti-CD19 chimeric antigen receptor (CAR) T-cells-associated Common Terminology Criteria for Adverse Events (CTCAE) ≥grade 3 cytopenia. In the EBMT CAR-T registry, we identified 398 adult patients with large B-cell lymphoma who had been treated with CAR-T-cells with axicel (62%) or tisacel (38%) before August 2021 and had cytopenia status documented for the first 100 days. Most patients had received two or three previous lines of therapy, however, 22.3% had received four or more. Disease status was progressive in 80.4%, stable in 5.0% and partial/complete remission in 14.6%. 25.9% of the patients had received a transplantation before. Median age was 61.4 years (min-max; IQR=18.7-81; (52.9-69.5)).The cumulative incidence of ≥grade 3 cytopenia was 9.0% at 30 days (95% CI (6.5 to 12.1)) and 12.1% at 100 days after CAR T-cell infusion (95% CI (9.1 to 15.5)). The median time from CAR-T infusion to cytopenia onset was 16.5 days (min-max; IQR=1-90; (4-29.8)). Grade 3 and grade 4 CTCAE cytopenia occurred in 15.2% and 84.8%, respectively. In 47.6% there was no resolution.Severe cytopenia had no significant impact on overall survival (OS) (HR 1.13 (95% CI 0.74 to 1.73), p=0.57). However, patients with severe cytopenia had a poorer progression-free survival (PFS) (HR 1.54 (95% CI 1.07 to 2.22), p=0.02) and a higher relapse incidence (HR 1.52 (95% CI 1.04 to 2.23), p=0.03). In those patients who developed severe cytopenia during the first 100 days (n=47), OS, PFS, relapse incidence and non-relapse mortality at 12 months after diagnosis of severe cytopenia were 53.6% (95% CI (40.3 to 71.2)), 20% (95% CI (10.4 to 38.6)), 73.5% (95% CI (55.2 to 85.2)) and 6.5% (95% CI (1.7 to 16.2)), respectively.In multivariate analysis of severe cytopenia risk factors, only year of CAR-T infusion (HR=0.61, 95% CI (0.39 to 0.95), p=0.028) and total number of treatment lines before CAR-T infusion (one or two lines vs three or more, HR=0.41, 95% CI (0.21 to 0.83), p=0.013) had a significant positive association with the incidence of cytopenia. Other factors, such as previous transplantation, disease status at time of CAR-T, patient age and patient sex, had no significant association.Our data provide insight on frequency and clinical relevance of severe cytopenia after CAR T-cell therapy in the European real-world setting.

Similar outcomes following non-first-degree and first-degree related donor haploidentical hematopoietic cell transplantation for acute leukemia patients in complete remission: a study from the Global Committee and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

There are situations where non-first-degree (NFD) related donors have to be considered as alternatives to first-degree (FD) related donors for haploidentical hematopoietic cell transplantation (HAPLO). However, the efficacy of these NFD related transplants remains uncertain. All consecutive adult patients (≥ 18 years) with acute myelogenous leukemia (AML) or acute lymphocytic leukemia (ALL) in CR who underwent a first HAPLO between 2010 and 2021 in the European Society for Blood and Marrow Transplantation (EBMT) registry were analyzed. Exact matching and propensity score matching was used. The NFD-to-FD ratio was 1:3. 2703 patients (AML: n = 2047; ALL: n = 656) in CR received a first HAPLO from either NFD (n = 154) or FD (n = 2549) related donors in 177 EBMT centers. 123 NFD and 324 FD HAPLO were included for analysis after matching. Median patient age was 35.6 and 37.2 for the NFD and FD cohorts, respectively. Both cohorts reached good engraftment rates (NFD: 95.7% vs. FD, 95.6%; p = 0.78). The 2-year relapse incidence (NFD, 21.1% vs. FD, 22.6%; p = 0.84) and non-relapse mortality (NRM) (NFD, 13.2% vs. FD, 17.7%; p = 0.33) were not significantly different. The 2-year overall survival (OS) (NFD, 71.8% vs. FD, 68.3%; p = 0.56), leukemia-free survival (LFS) (NFD, 65.7% vs. FD, 59.7%; p = 0.6) and graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) (NFD, 50.9% vs. FD, 47.8%; p = 0.69) also showed no significant differences. The two cohorts showed no difference in terms of cumulative day 180 grade II-IV, grade III-IV acute GVHD, 2-year cumulative incidences of chronic and extensive chronic GVHD. For HAPLO in patients with acute leukemia, NFD related donors could be equivalent substitutions when FD related donors are not available.

Impact of donor kinship on non-T-cell depleted haploidentical stem cell transplantation with post transplantation cyclophosphamide for acute leukemia: From the ALWP of the EBMT.

Non-T-cell depleted haploidentical hematopoietic cell transplantation (Haplo-HCT) is a unique transplantation setting in which several donors are available. We assessed the impact of donor kinship on outcome of Haplo-HCT with post-transplantation cyclophosphamide in a cohort of 717 acute leukemia patients. We compared sibling with parent donors in patients ≤45 years, and child with sibling donors in patients >45 years. Donor kinship was not associated with worse outcomes in multivariate analysis. For patients ≤45 years, the hazard ratio (HR) for leukemia-free survival (LFS), overall survival (OS), relapse incidence (RI), and chronic graft-versus-host disease (cGVHD) was 0.87 (p = 0.75), 1.19 (p = 0.7), 0.52 (p = 0.19), and 0.99 (p = 0.97) for parents versus siblings, respectively, and for patients >45 years the HR was 0.93 (p = 0.8), 0.98 (p = 0.94), 1.3 (p = 0.53), and 0.98 (p = 0.95) for children versus siblings, respectively. Univariate incidence of acute GVHD grade II-IV was significantly higher in patients transplanted from siblings versus children (p = 0.002). Factors associated with inferior outcome were advanced disease and earlier transplant. In patients ≤45 years, acute lymphocytic leukemia and peripheral blood stem cell graft were additional prognostic factors for OS. We did not find a significant impact of donor kinship on transplantation outcome when analyzing by age group (≤45 and >45 years).

Measurable residual disease status and outcome of transplant in acute myeloid leukemia in second complete remission: a study by the acute leukemia working party of the EBMT.

Measurable residual disease (MRD) prior to hematopoietic cell transplant (HCT) for acute myeloid leukemia (AML) in first complete morphological remission (CR1) is an independent predictor of outcome, but few studies address CR2. This analysis by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation registry assessed HCT outcomes by declared MRD status in a cohort of 1042 adult patients with AML CR2 at HCT. Patients were transplanted 2006-2016 from human leukocyte antigen (HLA) matched siblings (n = 719) or HLA 10/10 matched unrelated donors (n = 293). Conditioning was myeloablative (n = 610) or reduced-intensity (n = 432) and 566 patients (54%) had in-vivo T cell depletion. At HCT, 749 patients (72%) were MRD negative (MRD NEG) and 293 (28%) were MRD positive (MRD POS). Time from diagnosis to HCT was longer in MRD NEG than MRD POS patients (18 vs. 16 months (P < 0.001). Two-year relapse rates were 24% (95% CI, 21-28) and 40% (95% CI, 34-46) in MRD NEG and MRD POS groups (P < 0.001), respectively. Leukemia-free survival (LFS) was 57% (53-61) and 46% (40-52%), respectively (P = 0.001), but there was no difference in terms of overall survival. Prognostic factors for relapse and LFS were MRD NEG status, good risk cytogenetics, and longer time from diagnosis to HCT. In-vivo T cell depletion predicted relapse.

Evaluation of six different types of sequential conditioning regimens for allogeneic stem cell transplantation in relapsed/refractory acute myelogenous leukemia - a study of the Acute Leukemia Working Party of the EBMT.

The Acute Leukemia Working Party (ALWP) of the EBMT assessed the outcome of allogeneic stem cell transplantation (alloSCT) in patients with relapsed/refractory AML (r/rAML) evaluating six sequential conditioning regimens (SR) groups. A total of 2132 patients were included. LFS at 2 years was 28.9%, 33.6%, 35.3%, 20.6%, 24.4%, and 27% for the FLAMSA-TBI4, FLAMSA-Chemo, Mel-Flu-TBI8, Mel-Treo-Flu, Thio-ETO-Cy-Bu2-Flu, and Clo-ARAC-(Bu2/TBI4)-Cy groups, respectively. In patients <55 years of age Mel-Flu-TBI8 had the best LFS, which was statistically significant only in comparison to the Mel-Treo-Flu group, while in patients ≥55 years LFS was best with FLAMSA-Chemo without significant differences compared to FLAMSA-TBI4 and Mel-Flu-TBI8. Furthermore, best NRM rates were obtained with the two FLAMSA regimens groups. Our study suggests that in younger (<55 years) patients a more intense regimen might be used whereas in older (≥55 years) patients the focus might be more on tolerability.

Comparison of reduced-intensity conditioning regimens in patients with acute lymphoblastic leukemia >45 years undergoing allogeneic stem cell transplantation-a retrospective study by the Acute Leukemia Working Party of EBMT.

The optimal reduced-intensity conditioning (RIC) for patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. We retrospectively analyzed 417 patients > 45 years with ALL in first complete remission who underwent a matched sibling or unrelated allo-HSCT and compared outcomes between fludarabine/busulfan (FLUBU, n = 127), fludarabine/melphalan (FLUMEL, n = 190), and fludarabine-TBI (FLUTBI, n = 100) conditioning. At 2 years, there were no differences between the groups in terms of cumulative incidence (CI) of relapse (40% for FLUBU vs 36% for FLUMEL vs 41% for FLUTBI, p = 0.21); transplant-related mortality (TRM) (18% for FLUBU, 22% for FLUMEL, 14% for FLUTBI, p = 0.09); overall survival (55% for FLUBU, 50% for FLUMEL, 60% for FLUTBI, p = 0.62) or leukemia-free survival (43% for FLUBU, 42% for FLUMEL, 45% for FLUTBI, p = 0.99), but GVHD-relapse-free survival was significantly lower in the FLUTBI group than FLUBU and FLUMEL group (18% vs 35% vs 28%, p = 0.02). However, this difference was lost in the multivariate analysis when adjusted for the in vivo T-cell depletion. Finally, the FLUMEL regimen was shown to be an independent risk factor for a higher TRM (HR 1.97, 95% CI 1.05-3.72, p = 0.04). We conclude that the three most popular RIC regimens yield similar transplant outcomes.

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.

Allogeneic haemopoietic transplantation for acute myeloid leukaemia in second complete remission: a registry report by the Acute Leukaemia Working Party of the EBMT.

Allogeneic haemopoietic cell transplant (allo-HCT) may be curative in acute myeloid leukaemia (AML) in second complete remission (CR2) but the impact of reduced intensity (RIC) versus myeloablative conditioning (MAC) is uncertain. The Acute Leukaemia Working Party of the European Society for Blood and Bone Marrow Transplantation Registry studied an AML CR2 cohort characterised by age ≥ 18 years, first allo-HCT 2007-2016, available cytogenetic profile at diagnosis, donors who were matched family, volunteer unrelated with HLA antigen match 10/10 or 9/10 or haplo-identical. The 1879 eligible patients included 1010 (54%) MAC allo-HCT recipients. In patients <50 years (y), two year outcomes for MAC vs RIC allo-HCT were equivalent with leukaemia-free survival (LFS) 54% for each, overall survival (OS), 61% vs 62%, non-relapse mortality (NRM) 18% vs 15% and graft versus host disease relapse-free survival (GRFS) 38% vs 42%. In patients ≥50 y, 2 y outcomes for MAC vs RIC allo-HCT were equivalent for LFS 52% vs 49%, OS 58% vs 55% and GRFS 42.4% vs 36%. However, NRM was significantly inferior after MAC allo-HCT, 27% vs 19% (P = 0.01) despite worse cGVHD after RIC-allo (32% vs 39%). These data support the need for ongoing prospective study of conditioning intensity and GVHD mitigation in AML.

Allogeneic stem cell transplantation using HLA-matched donors for acute myeloid leukemia with deletion 5q or monosomy 5: a study from the Acute Leukemia Working Party of the EBMT.

Deletion 5q or monosomy 5 (-5/5q-) in acute myeloid leukemia (AML) is a common high-risk feature that is referred to allogeneic stem cell transplantation. However, -5/5q- is frequently associated with other high-risk cytogenetic aberrations such as complex karyotype, monosomal karyotype, monosomy 7 (-7), or 17p abnormalities (abn (17p)), the significance of which is unknown. In order to address this question, we studied adult patients with AML harboring -5/5q- having their first allogeneic transplantation between 2000 and 2015. Five hundred and one patients with -5/5q- have been analyzed. Three hundred and thirty-eight patients (67%) were in first remission and 142 (28%) had an active disease at time of allogeneic transplantation. The 2-year probabilities of overall survival and leukemia-free survival were 27% and 20%, respectively. The 2-year probability of treatment-related mortality was 20%. We identified four different cytogenetic groups according to additional abnormalities with prognostic impact: -5/5q- without complex karyotype, monosomal karyotype or abn(17p), -5/5q- within a complex karyotype, -5/5q- within a monosomal karyotype and the combination of -5/5q- with abn(17p). In multivariate analysis, factors associated with worse overall survival and leukemia-free survival across the four groups were active disease, age, monosomal karyotype, and abn(17p). The presence of -5/5q- without monosomal karyotype or abn(17p) was associated with a significantly better survival rate while -5/5q- in conjunction with monosomal karyotype or abn(17p) translated into a worse outcome. The patients harboring the combination of -5/5q- with abn(17p) showed very limited benefit from allogeneic transplantation.

Stem cell transplantation from a haploidentical donor versus a genoidentical sister for adult male patients with acute myelogenous leukemia in first remission: A retrospective study from the acute leukemia working party of the European Society for Blood and Marrow Transplantation.

BACKGROUND: In adult patients with acute myeloid leukemia (AML), a matched sibling donor (MSD) is considered the first choice for an allogeneic transplantation. However, a female donor for a male recipient is a poor prognostic factor. The authors compared haploidentical (HAPLO) donors with female MSDs. METHODS: In total, 834 men underwent allogenic transplantation from a female MSD, and 232 men underwent allogenic transplantation from a HAPLO donor. Of these, 86% of HAPLO recipients and 3% of MSD recipients received graft-versus-host disease (GVHD) prophylaxis posttransplantation with high-dose cyclophosphamide. A significant qualitative interaction was observed between donor type and cytogenetics, Therefore, the analyses were stratified on cytogenetics. RESULTS: Of the men with intermediate-risk AML, 638 received transplantation from a female MSD, and 160 received transplantation from a HAPLO donor. In multivariate analysis, poor risk factors were a HAPLO donor versus an MSD for nonrelapse mortality (hazard ratio [HR], 1.7; P = .02) and patient age for nonrelapse mortality and overall survival (HR, 1.22 [P = .02] and 1.15 [P = .02], respectively). HAPLO transplantation resulted in less chronic GVHD (HR, 0.43; P < 10-4 ) but lower leukemia-free survival (HR, 1.7; P = .04). The GVHD/relapse-free survival (GRFS) was not different. Of the men with high-risk AML, 196 received transplantation from a female MSD, and 72 received transplantation from a HAPLO donor. By multivariate analysis, HAPLO recipients had a lower incidence of relapse (HR, 0.40; P = .004), better leukemia-free survival (HR, 0.46; P = .003), better overall survival (HR, 0.43; P = .003), and better GRFS (HR, 0.54; P = .006). CONCLUSIONS: In men who have intermediate-risk AML, allogenic transplantation from a sister MSD or a HAPLO donor produces similar GRFS. However, in men who have high-risk AML, a HAPLO donor combined with prophylactic high-dose cyclophosphamide posttransplantation may be a better choice.

Fludarabine/busulfan versus fludarabine/total-body-irradiation (2 Gy) as conditioning prior to allogeneic stem cell transplantation in patients (≥60 years) with acute myelogenous leukemia: a study of the acute leukemia working party of the EBMT.

Nonmyeloablative (NMA) conditioning regimens facilitate allogeneic stem cell transplantation (alloSCT) in elderly patients and/or in those with comorbidities. The acute leukemia working party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT) compared the outcomes of patients ≥60 years with AML in first complete remission (CR1), that had received an alloSCT following NMA conditioning, i.e. either fludarabine/busulfan (FB2) or fludarabine/total-body-irradiation-2Gy (FluTBI2Gy). A total of 1088 patients were included (median age 65 years). Donors were matched siblings (MSD) and matched unrelated donors (MUD) in 47% and 53%, respectively. In vivo T-cell depletion (TCD) was applied to 79% and none (0%) of patients in the FB2 and FluTBI2Gy groups, respectively. In the MSD group we found a trend for less extensive cGVHD in patients receiving FB2 with in vivo TCD, HR: 0.49, p = 0.08, and in those without worse NRM, HR: 2.14, p = 0.04, and a trend for more total cGVHD, HR: 1.61, p = 0.09. Patients transplanted from MUDs had a significantly higher incidence of total cGVHD, extensive cGVHD and a worse GRFS with FluTBI2Gy in comparison to FB2, HR: 2.44; p < 0.0001; HR 4.59; p < 0.00001 and HR: 1.35; p = 0.03, respectively. No differences were observed with respect to LFS, OS, RI, NRM, and aGVHD.