Allogeneic Blood Stem Cell Transplantation Research Articles

Day 4 vs. day 12 G-CSF administration following reduced intensity peripheral blood allogeneic stem cell transplant.

Granulocyte colony-stimulating factor (G-CSF) hastens neutrophil engraftment and reduces infections after allogeneic hematopoietic cell transplant (alloHCT), yet the optimal start date is unknown. Additionally, concurrent G-CSF and methotrexate for graft-vs-host disease (GVHD) prophylaxis may potentiate myelosuppression, and prolonged G-CSF is costly. Our institution changed from day + 4 to day + 12 G-CSF initiation following reduced intensity (RIC) alloHCT with methotrexate GVHD prophylaxis. We retrospectively compared day + 4 and day + 12 G-CSF initiation after RIC alloHCT from 2017-2021. The primary endpoint was the time to neutrophil engraftment. Secondary endpoints included length of stay (LOS) and the time to platelet engraftment as well as the incidence of infectious events, acute GVHD (aGVHD), and mucositis. Thirty-two patients were included in each group with similar baseline characteristics. We observed faster neutrophil engraftment (median 12 vs. 15 days, p = 0.01) and platelet engraftment (median 13 vs. 15 days, p = 0.026) with day + 4 vs. day + 12 G-CSF initiation. Median LOS was 23 days (range, 19-32) with day + 4 initiation vs. 24 days (21-30) with day + 12 (p = 0.046). The incidence of culture-negative febrile neutropenia (p = 0.12), any grade aGVHD (p = 0.58), and grade 2-4 mucositis (p = 0.8) were similar between groups. Compared to day + 4, day + 12 G-CSF initiation following RIC alloHCT had a longer time to neutrophil and platelet engraftment. Day + 12 initiation also resulted in longer LOS, which while statistically significant, was potentially of limited clinical significance. These findings are hypothesis generating.

Relapsed acute myeloid leukemia presenting as conjunctival myeloid sarcoma: a case report

BackgroundConjunctival myeloid sarcoma (MS) as an isolated presentation of acute myeloid leukemia (AML) relapse is rare. Here, we report a case of unilateral conjunctival MS revealed as a sign of AML relapse.Case presentationA 50-year-old man with a history of AML in remission visited our clinic presenting with a left conjunctival injection persisting for 1 month. Diffuse subconjunctival thickening with conjunctival vascular engorgement was observed. Ultrasound biomicroscopy revealed a hyper-reflective, thickened conjunctiva in his left eye. During the incisional biopsy, the lesion was strongly attached to the underlying sclera; histopathologic examination revealed infiltration of leukemic blasts. The relapse of AML was confirmed by a successive bone marrow biopsy. The ocular lesion disappeared after allogeneic peripheral blood stem cell transplantation (PBSCT) and concomitant salvage radiotherapy on the left eye. The patient has remained in remission for 3 years after allogeneic PBSCT.ConclusionsIncidental conjunctival lesions can indicate AML relapse in patients treated earlier for AML. An ophthalmologist may have a role in the early detection of AML when a patient presents with an atypical conjunctival lesion.

A retrospective single-center analysis of G-CSF-mobilized donor lymphocyte infusion in hematologic malignancies after unmanipulated allogenic PBSCT.

To explore the efficacy and safety of G-SCF-mobilized donor lymphocyte infusion (DLI) for treatment of relapse of hematologic malignancies after allogeneic peripheral blood stem cell transplantation, we performed a retrospective analysis in a cohort of patients with morphologic (n = 36) or molecular (n = 22) relapse post transplantation. The 3-year post-DLI survival rates for therapeutic and preemptive DLI recipients were 16.7% and 33.3%, respectively. The occurrence of DLI-associated acute graft-versus-host disease predicted longer survival, whereas diagnosis of T cell acute lymphoblastic leukemia/lymphoma or myelodysplastic syndromes or early relapse after transplant (< 6months) predicted shorter survival after therapeutic DLI. Cumulative incidence of progression to hematologic relapse and non-relapse mortality after preemptive DLI were 46.8% and 29.1%, respectively. Active disease prior to transplant and early molecular relapse after transplant (< 4months) were the strongest predictors of non-relapse mortality after preemptive DLI. In conclusion, although therapeutic DLI had limited efficacy against T cell acute lymphoblastic leukemia/lymphoma or myelodysplastic syndromes or early post-transplant relapse, patients who developed DLI-associated acute graft-versus-host disease would benefit from this procedure in the setting of G-SCF-mobilized DLI. Furthermore, preemptive DLI could protect half of patients from hematologic relapse after transplantation with acceptable toxicity.

Total Body Irradiation–Based Conditioning Regimen Improved the Survival of Adult Patients With T-Cell Lymphoblastic Lymphoma After Allogeneic Peripheral Blood Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the consolidation modalities for adult patients with T-cell lymphoblastic lymphoma (T-LBL). However, the optimal conditioning regimen needs to be explored. In the present study, 40 patients with T-LBL undergoing allo-HSCT were retrospectively analyzed, including 23/40 (57.5%) with total body irradiation (TBI)–based conditioning regimen and 17/40 (42.5%) with busulfan (BU)-based regimen. TBI–based regimen significantly increased the cumulative incidence (CI) of grade II to IV acute graft-versus-host disease (aGvHD) as compared with BU-based regimen (13.0% vs 0%, P = 0.000). The relapse risk was significantly lowered in TBI-based group with a 2-year CI of relapse (CIR) of 9.1% as compared with that of 49.6% in BU-based group (P = 0.008). The 1-year and 2-year non-relapse mortalities (NRMs) for all patients were 5.0% and 10.3%, respectively. The 1-year and 2-year NRMs were 8.9% and 16.0% in TBI-based group, and 0.00% and 0.00% in BU-based group (P = 0.140). The 2-year probabilities of overall survival (OS) and relapse-free survival (RFS) were 83.0% [95% confidence interval, 63.4%–100%] and 74.0% (95% confidence interval, 54.4%–93.6%) in TBI-based group, which were higher than that of 35.0% (95% confidence interval, 0.0%–72.2%) and 50.0% (95% confidence interval, 24.5%–75.4%) in BU-based group, respectively (P = 0.020 for OS and P = 0.081 for RFS). In multivariate analysis, TBI-based regimen significantly reduced the risk of relapse [subdistribution hazard ratio (SHR) = 0.030, 95% CI, 0.002–0.040, P = 0.000] and improved the OS [hazard ratio (HR) 0.121, 95% CI, 0.021–0.683, P = 0.017] as an independent prognostic factor. These results suggested that TBI-based regimen might be an optimal choice for adult patients with T-LBL undergoing allo-HSCT.

HLA-haploidentical peripheral blood stem cell transplantation with post-transplantation cyclophosphamide for adult T-cell leukemia

Recently, allogeneic peripheral blood stem cell transplantation from human leukocyte antigen (HLA)-haploidentical donors using post-transplantation cyclophosphamide (PTCY-haploPBSCT) has become available in clinical practice. However, the efficacy of PTCY in adult T-cell leukemia (ATL) is not fully established yet. In this study, we retrospectively examined data of seven patients who underwent PTCY-haploPBSCT. The overall survival rate at 100 days after transplantation was 85.7%, and the 1-year overall survival rate was 68.6%. The cumulative incidence of relapse at 1 year was 31.4%, whereas the 1-year nonrelapse mortality was 17.1%. The cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD) on day 100 was 14.3%, and the incidence of chronic GVHD at 1 year was 33.3%. These results suggest that PTCY-haploPBSCT can be a viable option even in patients with ATL. Further accumulation of knowledge and improvement of transplantation outcomes are warranted in the future.

Association of CD34 Cell Dose with 5-Year Overall Survival after Peripheral Blood Allogeneic Hematopoietic Cell Transplantation in Adults with Hematologic Malignancies

Higher CD34 cell dose is associated with improved engraftment after peripheral blood allogeneic hematopoietic stem cell transplantation (alloHCT) but also may increase the risk of long-term complications, such as graft-versus-host disease (GVHD). Prior studies examining the relationship between CD34 cell dose and long-term survival outcomes have yielded conflicting results. In this study, we sought to clarify the prognostic impact of CD34 cell dose by examining a large contemporary cohort of patients undergoing alloHCT with a matched sibling peripheral blood stem cell (PBSC) donor. We retrospectively examined the impact of CD34 cell dose on overall survival (OS), neutrophil engraftment, platelet engraftment, treatment-related mortality, relapse, acute GVHD grade II-IV and III-IV, and chronic GVHD in 377 consecutive patients undergoing alloHCT with a PBSC graft source from a matched sibling donor at the University of Minnesota between 2002 and 2015. The patients were classified into 3 groups based on the tertile (T) of CD34 cell dose received: T1, <5×106 cells/kg; T2, 5 to 7.5×106 cells/kg; and T3, ≥7.5×106 cells/kg. Multivariable analysis demonstrated that high CD34 cell dose was associated with superior 5-year OS (hazard ratio [HR], 0.57; P=.01) and more rapid platelet engraftment (HR, 1.70; P < .01). Higher CD34 cell dose also was associated with improved absolute neutrophil count engraftment (T2: HR, 1.54; T3: HR, 1.52; P < .01). There was no association between CD34 cell dose and TRM or relapse at 5 years. Although higher CD34 cell dose was not associated with acute GVHD grade II-IV, it was associated with chronic GVHD (T2: HR, 1.68; T3: HR, 1.50; P=.04). Our data indicate that higher CD34 cell dose (>7.5×106/kg) is associated with superior OS at 5 years and improved engraftment but carries an increased risk of chronic GVHD. These data support a target CD34 cell dose goal of 7.5×106/kg for sibling PBSC graft donors.

Treatment of MDS, AML and CMML Relapse after Allogeneic Blood Stem Cell Transplantation with Azacitidine, Lenalidomide and Donor Lymphocyte Infusions - Final Results of the Prospective Azalena-Trial (NCT02472691)

BackgroundAzacitidine (Aza) in combination with donor lymphocyte infusions (DLI) is an established treatment option for pts with relapse of myeloid malignancies after allo-SCT. Accounting for its immunomodulatory and anti-leukemic properties, we considered Lenalidomide (Len) to be a synergistic partner for Aza and DLI that may further improve response rate and outcome. To investigate the tolerability and efficacy of the combination of Aza, Len and DLI as first salvage therapy for relapsed MDS, AML and CMML after allo-SCT we performed a prospective, multicenter, single-arm phase-II trial. Results from two safety interim analyses have previously been reported. Here, we report the final results from this investigator-initiated trial.Design/Methods:Patients with relapse of MDS, AML and CMML after first allo-SCT were eligible. Envisaged treatment according to the protocol consisted of up to 8 cycles Aza (75 mg/m 2/d d1-7, every 28 days) and up to 3 DLI with increasing T cell dosages (0.5×10 6 - 1.5×10 7 cells/kg). Len was administered concomitantly for 21 days of a 28-day cycle. Following a positive first interim safety analysis in 10 patients the daily dose of Len was increased from 2.5 to 5mg. The primary endpoint of the study was safety, while secondary efficacy endpoints included response type and rates, time to and duration of response and overall survival.Results:Overall, 50 pts with molecular (n=29, 58%) or hematological (n=21, 42%) relapse of MDS (n=24, 48%), AML (n=23, 46%) or CMML (n=3, 6%) detected after median of 233 days (range, 98 to 2659) after allo-SCT were included. Fourteen patients (28%) received Len at a daily dosage of 2.5 mg and 36 patients (72%) at a daily dosage of 5 mg with no DLTs observed in the interim analyses. Median number of Len cycles per patient was 7 (range, 1 to 8) with no differences between the two dose levels. Concomitantly, 34 pts (68%) received at least one DLI (median: 3, range: 1-11).Overall response rate (ORR) during treatment was 56% (CR n=25, 50%, PR n=3, 6%). ORR and CR rates did not differ between Len dose levels. Of interest, CR rate did not differ between pts treated at the stage of molecular relapse and those initiated at hematological relapse (52% vs. 48%). Median time to CR was 112 days (range 1-286) corresponding to 4 cycles (range 1 to 8). At the time of data lock, 20 patients (80%) were still in CR without additional therapy for a median of 15 months, while 5 patients (20%) had relapsed again after a median of 8 months. With a median follow-up of 20 months median OS was 21 months and 1-year OS rate 65%.While therapy-related CTC grade III/IV neutropenia (92%), thrombopenia (80%) or anemia (36%) occurred frequently, drug-related non-hematological adverse events (AE) >grade II were rare and mainly consisted of gastrointestinal toxicity (6%), laboratory findings (28%) and infections (22%). Twenty-three pts (46%) developed acute GvHD including 5 patients (10%) with grade III/IV aGvHD, and 26 pts (52%) chronic GvHD (mild n=10; moderate n=11; severe n=5). During the study period, 3 secondary malignancies (squamous cell, basal cell and vulvar carcinoma) occurred. There were no therapy related deaths.Conclusion:Len up to a dosage to 5 mg/day can be safely added to the combination of AZA and DLI without excess of GvHD and toxicity. Furthermore, these data suggest that the combination of Aza, Len and DLI has promising clinical activity for relapse of myeloid malignancies after allo-SCT and is able to induce durable responses and survival in a substantial proportion of pts. DisclosuresSchroeder: Celgene: Honoraria, Other: Travel support, Research Funding. Stelljes: Kite/Gilead: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Celgene/BMS: Consultancy, Speakers Bureau; Medac: Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau. Holtick: Celgene: Honoraria; Sanofi: Honoraria. Germing: Janssen: Honoraria; Bristol-Myers Squibb: Honoraria, Other: advisory activity, Research Funding; Jazz Pharmaceuticals: Honoraria; Celgene: Honoraria; Novartis: Honoraria, Research Funding. Kröger: AOP Pharma: Honoraria; Celgene: Honoraria, Research Funding; Gilead/Kite: Honoraria; Jazz: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Novartis: Honoraria; Riemser: Honoraria, Research Funding; Sanofi: Honoraria. Kobbe: Celgene: Research Funding. OffLabel Disclosure:Lenalidomide is not licensed for AML, CMML and advanced MDS except for MDS with isolated del5q

Two Cases of Tacrolimus-related Transplant-associated Thrombotic Microangiopathy Retinopathy after Allogenic Peripheral Blood Stem Cell Transplantation

Purpose: We report two cases of tacrolimus-related transplant-associated thrombotic microangiopathy (TA-TMA) retinopathy in leukemia patients who had undergone allogenic peripheral blood stem cell transplantation (PBSCT).Case summary: (Case 1) A 58-year-old woman with a history of PBSCT due to acute myelocytic leukemia and taking tacrolimus was referred to the ophthalmology clinic with visual disturbance. Her visual acuity (VA) was 0.4 in the right eye and 0.5 in the left eye. Multiple cotton wool spots and retinal hemorrhages were found in both eyes on fundus examination. Multiple capillary non-perfusions were seen on fluorescein angiography (FA). Tacrolimus-related TA-TMA retinopathy was suspected. Tacrolimus was discontinued and plasmapheresis was performed. After 3 months, neovascular glaucoma developed and her VA became “counting fingers” at 20 cm in both eyes. (Case 2) A 20-year-old man with a history of PBSCT due to acute lymphocytic leukemia and taking tacrolimus was referred to our clinic because of decreased VA in both eyes. His VA was 0.05 in the right eye and 0.025 in the left eye. Fundus and FA findings were the same as in Case 1, and the patient was suspected to have tacrolimus-related TA-TMA retinopathy. Tacrolimus was discontinued and plasmapheresis was performed. His VA was 0.2 in the right eye and 0.4 in the left eye at 1 month after treatment.Conclusions: It is necessary to consider TA-TMA retinopathy in leukemia patients taking calcineurin inhibitors, such as tacrolimus, who have decreased VA. Early diagnosis and treatment are important.

Desquamative esophagitis followed by esophageal cancer in a stem cell transplant recipient

A 69-year-old Japanese woman with acute myeloid leukemia underwent allogeneic peripheral blood stem cell transplantation from a human leukocyte antigen (HLA)-matched unrelated donor. After transplantation, tacrolimus was not discontinued because of persistent graft-versus-host disease (GVHD) of the liver. EGD performed 2 years after transplantation revealed no esophageal abnormalities except for reflux esophagitis. She described discomfort while swallowing 3 years after transplantation and received a diagnosis of chronic GVHD of the oral mucosa.

Poster: CT-210: Sirolimus and Post-Transplant Cyclophosphamide as Graft-versus-Host Prophylaxis in Patients Undergoing Matched Allogeneic Peripheral Blood Stem Cell Transplantation

Poster: CT-210: Sirolimus and Post-Transplant Cyclophosphamide as Graft-versus-Host Prophylaxis in Patients Undergoing Matched Allogeneic Peripheral Blood Stem Cell Transplantation

CT-210: Sirolimus and Post-Transplant Cyclophosphamide as Graft-versus-Host Prophylaxis in Patients Undergoing Matched Allogeneic Peripheral Blood Stem Cell Transplantation

Context Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for high-risk malignancies, although graft-versus-host (GVH) disease limits optimal outcomes. Post-transplant cyclophosphamide (PTCy) is an effective agent for the prophylaxis of GVH due to its functional inhibition of alloreactive T-lymphocytes and may enable GVH prevention while preserving the graft-versus-tumor effect. Additional data are needed to inform the use of PTCy when using fully matched donors. Objective To determine the rate of GVH, relapse, and overall survival following allogeneic HCT from fully matched donors using sirolimus/PTCy as GVH prophylaxis. Design Retrospective data were collected on 14 consecutive patients transplanted with a fully matched donor between November 2016 and June 2018 who received PTCy (day +3–4) and sirolimus (day +5) for GVH prophylaxis. Data collected included age, disease risk, HCT-CI, GVH incidence and grade, 1-yr overall survival, median survival, and GRFS. Patients or Other Participants 14 consecutive patients transplanted at BMDACC who received GVH prophylaxis with sirolimus and PTCy. All received thiotepa/fludarabine/melphalan conditioning. Results Disease risk index was intermediate (9), high (3), or very high (2). 7 with AML, 5 with MDS/MPN. Median age 69 yrs (39–81). Donor-related in 4, unrelated in 10, and all PBSC. Median days on sirolimus: 53 (5–238). Median overall survival was 908 days. 1-yr OS was 64%, and NRM was 28%. There was 1 case of VOD/SOS, 3 infectious deaths, and 1 due to CVA. Relapse-free survival median: 861 days (17–1362) and GRFS median: 565 days (17–1362). Incidence of all-grade GVH was 42%, with no grade 3/4 GVH and 7% cGVH. One patient relapsed. Seven of the 14 patients remain alive and disease-free at the time of this abstract, with a median follow-up of 3 yrs. Conclusions GVH prophylaxis with PTCy and sirolimus led to a low rate of grade 3/4 GVH and cGVH within this population. Relapse risk remained low, suggesting preserved graft-versus-tumor effect. Infectious deaths may be related to the timing of immune reconstitution following PTCy. Additional data are needed to inform the use of PTCy in the setting of fully matched donors.

A retrospective comparative cohort study on the routine pre-engraftment use of granulocyte colony-stimulating factor in allogeneic hematopoietic stem cell transplantation

Objective: Myeloid growth factors have been often used in allogeneic hematopoietic stem cell transplantation settings. There are some controversies about increased graft versus host disease, relapse, and delayed platelet engraftment with those growth factors in the pre-engraftment period. In this study, we aimed to compare the transplantation outcomes of allogeneic hematopoietic stem cell transplantation recipients according to their myeloid growth factor support status.&#x0D; Materials and Methods: Sixty-seven adult acute myeloid leukemia/myelodysplastic syndrome and acute lymphoblastic leukemia patients who underwent allogeneic peripheral blood stem cell transplantation from HLA-identical matched sibling donors were analyzed retrospectively. All-cause mortality at day 100, day 180, and at 1-year were the primary outcome measures. Secondary outcome measures were the engraftment kinetics, length of hospital stay, and graft-versus-host disease incidences.&#x0D; Results: Growth factor supported group was younger (p=0.001), and the first complete remission status at transplantation was seen more compared to the unsupported group (p=0.04). Myeloablative conditioning was used more in growth factor supported group (p=0.004). Faster neutrophil engraftment (p=0.008) and delayed platelet engraftment (p=0.022) were seen in growth factor supported group. Graft-versus-host disease, relapse incidences, and all-cause mortality at day 100, day 180, and at 1-year were not different between groups. Steroid-resistant graft-versus-host disease was the only factor related with relapse (OR: 0.196, p=0.043).&#x0D; Conclusion: This real-life study shows colony-stimulating-factors are safe in HLA-identical sibling allogeneic hematopoietic stem cell transplantation. Further prospective randomized controlled studies for different stem cell sources, different donors, and different conditioning and graft-versus-host disease prophylaxis regimens are mandatory.

The Impact of Graft CD3 Cell/Regulatory T Cell Ratio on Acute Graft-versus-Host Disease and Post-Transplantation Outcome: A Prospective Multicenter Study of Patients with Acute Leukemia Undergoing Allogeneic Peripheral Blood Stem Cell Transplantation

Although it is well known that tumor site- or bone marrow-infiltrating regulatory T cells (Tregs) might be correlated with worse outcomes in solid tumors and acute leukemias by promoting immune surveillance escape, their contribution to the immediate post-allogeneic transplantation phase by peripheral blood (PB) allografts remains unclear. Moreover, the Treg content in stem cells harvested from PB has been suggested to be correlated with acute graft versus-host-disease (aGVHD) and immunologic recovery after allogeneic PB stem cell transplantation (allo-PBSCT). This study aimed to investigate the impact of the graft content of Tregs, as graft CD3+/Tregs ratio (gCD3/TregsR), on acute GVHD and post-allo-PBSCT outcomes. We prospectively enrolled 94 consecutive patients at 9 Italian centers of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) with acute myelogenous (n=71; 75%) or lymphoblastic (n=23; 25%) leukemia in complete remission who underwent matched related donor (n=35; 37%) or unrelated donor (n=59; 63%) allo-PBSCT. The median graft CD3+ cell, Treg, and gCD3/TregsR values were 196×106/kg body weight (range, 17 to 666×106/kg), 3×106/kg (range, 0.1 to 35×106/kg), and 71 (range, 1 to 1883), respectively. The discriminatory power of the gCD3/TregsR value to predict grade ≥II aGVHD was assessed by estimating the area under the receiver operating characteristic (ROC) curve (AUC). Any grade and grade ≥II aGVHD occurred in 24 (26%) and 17 (18%) allo-PBSCT recipients, respectively. By ROC analysis, AUC (0.74; 95% confidence interval [CI], 0.608 to 0.866; P=.002) identified 70 as the optimal gCD3/TregsR cutoff value predicting the appearance of grade ≥II aGVHD with 76% sensitivity and 71% specificity. Patients were subdivided into a high (ROC curve value ≥70) gCD3/TregsR group (HR; n=48) and a low (ROC curve value <70) gCD3/TregsR group (LR; n=46). The incidence of grade II-IV aGVHD was lower in the LR group compared with the HR group (9% [4 of 46] versus 27% [13 of 48]) in both univariate analysis (odds ratio [OR], 4.8; 95% CI, 1.44 to 16.17; P=.015) and multivariate analysis (OR, 5.0; 95% CI, 1.34 to 18.93; P=.017), whereas no differences were documented taking into account aGVHD of any grade. The overall survival, disease-free survival, nonrelapse mortality, and relapse rates at 2 and 3 years were 61% and 54%, 62% and 55%, 15% and 23%, and 27% and 30%, respectively. Of note, gCD3/TregsR did not significantly correlate with relapse (P=.135). Taken together, our data from this prospective multicenter study confirm the value of Tregs in preventing aGVHD while maintaining the graft-versus-leukemia effect. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Impact of CD34+ Stem Cell Dose on Engraftment Period in Allogeneic Peripheral Blood Stem Cell Transplanted Patients

Haematopoietic progenitor stem cells acquired from the peripheral blood have been increasingly used to treat patient with haematological malignancy. The success of the allogeneic peripheral blood stem cell transplantation (PBSCT) is significantly dependent on amount of CD34+ stem cell infused which will determine the rate of the haematopoietic recovery and engraftment. This study was aimed to correlate the amount of CD34+ cell infused with the period of engraftment. This retrospective study was conducted on 62 patients with haematopoietic malignancy who have received PBSCT at Universiti Kebangsaan Malaysia Medical Centre from year 2011 to 2015. The impact of CD34+ stem cell infusion on neutrophil and platelet engraftment and obtaining complete chimerism was studied. Patients were divided into two groups based on the amount of CD34+ stem cell. Group A consisted of 9 patients and infused with &lt;5x106 cells/kg CD34+ cell while Group B consisted of 53 patients and infused with ≥5x106 cells/kg CD34+ stem cell. Data were collected and analysed. Group B patients were significantly associated with faster neutrophil engraftment: 12 (10-14) days while group A were 15 (10-21) days, (p=0.002). Platelet engraftment was also faster in group B: 17(12-25) days compared to group A: 18 (15-30) days. Complete chimerism in group B occurred in 30 (15-90) days and in group A was 60 (30-240) days. Platelet engraftment (p=0.149) and complete chimerism (p=0.021) were not significantly influenced by the CD34+ cell count. This study has shown that infusion of ≥5x106 cells/kg CD34+ stem cell shorten the time to haematopoietic engraftment particularly of neutrophilic engraftment.

Treatment of Relapse of MDS, AML and CMML after Allogeneic Blood Stem Cell Transplantation with Azacitidine, Lenalidomide and Donor Lymphocyte Infusions - Results from the First Interim Analysis of the Azalena-Trial (NCT02472691)

Background:Azacitidine (Aza) and donor lymphocyte infusions have become a standard treatment of myeloid malignancies relapsing after allo-SCT. Studies so far showed response rates ranging from 10% to 75% following treatment with Aza with or without donor lymphocyte infusions (DLI) and particularly patients (pts) with MDS and AML with low disease burden seem to benefit most. Lenalidomide (Len), due to its immunomodulatory and antileukemic properties, may act synergistically with Aza and DLI.Design/Methods:We initiated a prospective, multicenter, single-arm phase-II trial combining Aza, Len and DLI in patients with MDS, AML or CMML as first salvage treatment for relapse after allo-SCT. Pts were envisaged to receive up to 8 cycles Aza (75 mg/m2/d d1-7, every 28 days) and 3 DLI with increasing dosages (0.5×106 - 1.5×107 cells/kg) after cycles 4, 6 and 8. Concomitantly, eight cycles of Len were administered with a daily dose of 2.5 mg for the first 21 days of a 28 day-cycle each.To cope with the potential risk of GvHD induction by Len after allo-SCT the primary endpoint is safety and the study incorporates two interim analyses scheduled after the first 10 and 20 patients respectively. If no dose limiting toxicity (DLT) defined as steroid refractory acute GvHD grade III/IV, chronic GvHD NIH score severe or any unexpected hematologic and non-hematological toxicity grade ≥ III is observed in more than 3 patients in the first interim analysis, the dose of Len will be increased to 5 mg/day for the next 10 patients. Otherwise the study will be stopped.Results:Here we present the results of the first interim analysis (data lock February 20th 2017), which includes 10 patients (median age: 64 years, range 43 to 73) who experienced molecular (70%) or hematological (30%) relapse of MDS (70%), AML (20%) or CMML (10%) after median of 275 days (range: 91 to 937) following allo-SCT. So far, these 10 patients have received a total of 54 cycles of Len corresponding to median of 7 cycles per patient (range: 1 to 8). In addition, patients received a median of 7 courses of Aza (range 1-8) and 7 of 10 pts (70%) received at least one DLI (median: 1, range: 0-5).No DLT was observed. Two patients either developed acute GvHD (20%, overall grade I and III) and chronic GvHD (20%, NIH score mild and moderate). Treatment-associated neutropenia, thrombocytopenia or anemia CTC grade III/IV occurred in 75%, 50% and 0% of the patients, respectively. Common adverse events were gastrointestinal side effects, elevation of liver enzymes as well as infections. Nevertheless, during the treatment period only 2 patients needed to be hospitalized. Although efficacy was not the major scope of this first interim analysis, of 7 evaluable patients (early drop-out of 3 patients) 4 (57%) achieved complete remission and 1 patient (14%) achieved partial remission resulting in overall response rate of 71%.Conclusion:This interim-analysis shows that the combination of Aza, Len (21x2.5 mg/cycle) and DLI as first salvage therapy for relapse after allo-SCT is safe and feasible and not associated with excess GvHD. According to the protocol, the dose of Lena will now be increased to 21x5 mg/cycle for the next 10 patients. Furthermore, due to the label extension of Aza, the inclusion criteria will also be amended to AML patients with >30% BM blasts. DisclosuresSchroeder:Celgene: Consultancy, Honoraria, Other: travel support. Rautenberg:Celgene: Other: travel support. Scheid:BMS: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Nachtkamp:Celgene: Other: Travel Support. Germing:Janssen: Honoraria; Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Kröger:RIEMSER Pharma: Research Funding; Novartis AG: Research Funding; Amgen Inc.: Speakers Bureau; Janssen Global Services, LLC: Speakers Bureau; Neovii Pharmaceuticals AG: Speakers Bureau; Novartis AG: Speakers Bureau; Sanofi: Speakers Bureau. Kobbe:Celgene: Other: Advisory Board, Research Funding.

Idarubicin Intensified Bucy Regimen in Allogeneic Peripheral Blood Stem Cell Transplantation for High-Risk Acute Myeloid Leukemia: A Multicenter, Randomized Study (NCT 01766375)

▪AbstractBackground: Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a potentially curative treatment in patients with acute myeloid leukemia (AML). The results of conventional BUCY regimen for high-risk acute myeloid leukemia (AML) are unsatisfactory because of higher relapse. Recent studies suggested survival advantage with idarubicin intensified BUCY regimen in Allo-HSCT for patients with high-risk AML.Methods: This study was a multi-center, open, randomized-control study on the effects and safety of idarubicin 60mg/m2 combined with BUCY pretreatment program or BUCY pretreatment program on the overall survival (OS) rate and disease-free survival (DFS) rate of AML in high-risk group over a period of 2 years, where 118 high-risk AML patients underwent allogeneic peripheral blood stem cell transplantation (Allo-PBSCT) were enrolled between December 2012 and March 2017, from sibling or unrelated donors with well-matched human leukocyte antigens. This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Guangxi Medical University and was registered at the Chinese Bone Marrow Transplant Registry (CBMTR) and ClinicalTrials.gov (NCT 01766375). The conditioning regimen of experimental group (IDA-BUCY group, n=61) were: 1) Idarubicin 20mg/m2 given intravenously (IV) for 3 days (day -12 to day -10); 2) Busulphan (BU) 0.8mg/kg given intravenously (IV) four times per day for 4 days (day -7 to day -4); 3) cyclophosphamide (CTX) (60 mg/kg/day) given IV for 2 days (day -3 to day -2). The conditioning regimen of active comparator (BUCY group, n=57) were: 1) Busulphan (BU) 0.8mg/kg given intravenously (IV) four times per day for 4 days (day -7 to day -4); 2) cyclophosphamide (CTX) (60 mg/kg/day) given IV for 2 days (day -3 to day -2). GVHD prophylaxis of sibling Allo-PBSCT consisted of a combination of cyclosporin A (CSA), methotrexate(MTX) and mycophenolate mofetil(MMF) regimen [BMT 2009; 43(1):61-67]. Unrelated Allo-PBSCT used CSA, MMF, MTX, and anti-thymocytes globulin (ATG, 2.5 mg/kg/day given IV for 4 days,days -4 to day -1) for the prevention of GVHD.Results: The two groups were well balanced according to disease status, cytogenetic risk, and other variables. Data cut off for survival follow-up was June 30, 2017. The median follow-up time was 19 months (range, 4 months to 54 months). Six patients (9.8%) in the IDA+BUCY group and 15 (26.3%) in the BUCY group relapsed. Thirty-eight patients (IDA+BUCY group n=13, BUCY group n=25) died during the conduct of this study. The cumulative rates of transplant related mortality (TRM) of IDA+BUCY group and BUCY group were 12.7% (95% confidence interval [CI], 6.3 to 25.7) and 28.6% (95% CI, 16.8 to 51.7) (P=0.186), respectively. The cumulative rates of relapse was lower for the IDA+BUCY group (13.7%, 95% CI, 6.2 to 30.2) than for the BUCY group (28.1%, 95% CI, 17.8 to 44.3) (P=0.030). The OS and DFS of IDA+BUCY group at 2 years were 75.2% (95% CI, 63.0 to 87.4) and 74.9% (95% CI, 58.4 to 84.9), respectively. The OS and DFS of BUCY group at 2 years were 51.2% (95% CI, 36.5 to 65.9) and 50.1% (95% CI, 34.0 to 63.9), respectively. (Fig 1)Conclusion: Our results demonstrate that Idarubicin intensified BUCY regimen could dramatically improve the survival of high-risk AML with low relapse and acceptable transplantation-related mortality. This strategy could be of great benefit for the treatment of patient with high-risk AML. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The Use of Anti-Thymocyte Globulin Is Associated with Decreased Risk of Chronic Graft-Versus-Host Disease without Impact on Survival after Allogeneic Peripheral Blood Stem Cell Transplantation for Adults with Philadelphia-Positive Acute Lymphoblastic Leukemia: An Analysis By the Acute Leukemia Working Party of the EBMT

BACKGROUNDAllogeneic hematopoietic stem cell transplantation (allo-SCT) is the standard of care for adults with Philadelphia-positive acute lymphoblastic leukemia (Ph-pos ALL). During the last decade mobilized peripheral blood stem cells (PBSCT) have become predominant source of graft for allo-SCT. However, as compared to bone marrow, PBSCT is associated with increased risk of chronic graft-versus-host disease (cGVHD). Attempts to reduce the cGVHD rate include the addition of anti-thymocyte globulin (ATG) to the conditioning regimen. The goal of this registry-based, retrospective study was to analyze the effect of ATG on results of allo-PBSCT in adults with Ph-pos ALL. PATIENTS AND METHODS1055 patients, aged 18-76 years, with Ph-pos ALL, treated with unmanipulated allo-PBSCT in first complete remission between 1997-2014 were included in the analysis. Conditioning regimen was myeloablative in 769 (72%) cases and based on total body irradiation in 608 (58%) cases. Among 590 transplantations from matched sibling donors, ATG was used in 95 (16%) patients. While, in the 8/8 HLA-matched unrelated setting 304/465 (65%) patients were treated with ATG. RESULTSIn a univariate analysis the use of ATG was associated with decreased incidence of the overall cGVHD (32% vs. 48%, p<0.001) and extensive cGVHD (14% vs. 22%, p=0.002) as well as a tendency to increased probability of survival free from grade III-IV acute GVHD, cGVHD and relapse (GRFS, 43% vs 36%, p=0.07). No significant difference could be demonstrated with regard to the incidence of grade II-IV acute GVHD (34% vs. 33%, p=0.59), grade III-IV acute GVHD (12.5% vs. 13%, p=0.68), relapse (25.5% vs. 27%, p=0.86) and non-relapse mortality (NRM, 19% vs. 18.5%, p=0.21), as well as probability of leukemia-free survival (LFS, 55% vs. 54.5%, p=0.95) and overall survival (OS, 68% vs. 67%, p=0.57). Among patients treated with ATG, original disease was the most frequent cause of death (40%) followed by infections (24%) and GvHD (21%). Respective proportions among those not treated with ATG were 36%, 23%, and 28%.In a multivariate model adjusted for other potential risk factors, the use of ATG was associated with reduced risk of the overall cGVHD (HR=0.53, p<0.001) and extensive cGVHD (HR=0.53, p<0.001) while increased risk of relapse (HR=1.34, p=0.03). No significant effect was found with regard to the risk of NRM (HR=0.78, p=0.15), a chance of LFS (HR=1.01, p=0.49) and OS (HR=0.87, p=0.27). CONCLUSIONSPatients with Ph-pos ALL treated with allo-PBSCT benefit from the use of ATG in terms of reduced risk of cGVHD without impact on survival. Increased risk of relapse, as shown in a multivariate model implicates the need for strict monitoring of minimal residual disease and either prophylactic or pre-emptive use of tyrosine kinase inhibitors after transplantation. Further studies are needed to explore potential role of the ATG brand and dose. DisclosuresMohty:Sanofi: Honoraria, Speakers Bureau.

Durable Remission of Refractory and Advanced Stage Mycosis Fungoides/Sezary Syndrome (MF/SS) Utilizing an “Outpatient” Alemtuzumab and Fludarabine-Based Reduced Intensity Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT)

Background:Advanced MF/SS carries a poor prognosis with most therapies failing to provide a long-term benefit. Allogeneic hematopoietic cell transplantation may result in durable remissions or clinically meaningful downstaging in a subset of patients. However, the risk of transplant related mortality has substantially curbed enthusiasm in the use of conventional allogeneic transplantation for this disease. In this study, we describe a novel allogeneic transplant approach in which a G-CSF mobilized, unmanipulated PBSC allograft from HLA-matched siblings was infused after conditioning with a regimen customized to maximally cytoreduce the disease and to provide the necessary immunosuppression to achieve sustained donor immune engraftment needed for the generation of a graft-vs-tumor effect (GVT). We theorized that this outpatient based reduced intensity transplant regimen would provide the essential tumor-debulking and a strategy to achieve sufficient degrees of donor T-cell chimerism necessary to result in the generation of curative GVT effects in patients with the most advanced forms of MF/SS.Patients and Methods:Between January 2004 and May 2014, 5 subjects (median age of 57, range 27-59) with refractory, advanced stage (III and IV) MF/SS who had failed a median 3 prior treatment regimens (range 2-7) underwent PBSCT following mostly outpatient conditioning with alemtuzumab (total of 193 mg), and fludarabine (total of 125 mg/m2). On day 0, subjects received a G-CSF mobilized unmanipulated PBSC allograft from an HLA identical sibling. CSA alone was used as GVHD prophylaxis. Donor lymphocyte infusions (DLI) were given to all patients to convert T-cell chimerism from mixed to full donor and when necessary to boost a GVT effect.Results:All 5 subjects initially had mixed lympho-hematopoietic chimerism but eventually converted to full donor chimeras in both myeloid and T-cell lineages; full donor T-cell chimerism was achieved at a median 7 months post-transplant (Figure 1). 3/5 subjects never became neutropenic and the 2 subjects who developed neutropenia had rapid neutrophil recovery occurring after 5 and 7 days. No patients developed severe anemia or thrombocytopenia and none required RBC or platelet transfusion support.No patients developed acute GVHD prior to DLI and only one (20%) developed acute GVHD (GI, grade IV) following DLI (the 2nd DLI for this patient). Three subjects (60%) developed limited cGVHD which resolved with short course of steroids.At a median follow-up of 3 years, 4 subjects achieved a complete remission, documented by labs, skin biopsy, and imaging. Remissions were delayed in onset, occurring at median 8 months post-transplant (Figure 1). 3 subjects remain alive in remission 13, 11, and 3 years after transplant. One subject with a heavy smoking history died in remission 3 years post-transplant from a secondary head and neck squamous cell carcinoma, and one subject died 7 months post-transplant from grade IV GI GVHD which followed a 2nd DLI given to treat progressive disease (Table 1).Among those at risk, 3 of 4 subjects (75%) developed CMV reactivation. None of the subjects developed CMV disease or PTLD.Conclusions:Our custom designed conditioning regimen 1) resulted in cytoreductive effects against advanced MF 2) proved to be immunosuppressive enough to allow sustained donor engraftment serving as a platform for subsequent DLIs which lead to curative GVT effects 3) could be performed in the outpatient setting avoiding severe neutropenia and its associated opportunistic infections and the need for platelet and RBC transfusion support. These data establish that long-term cures of even the most advanced refractory MF/SS can be achieved utilizing this alemtuzumab and fludarabine-based reduced intensity allogeneic hematopoietic cell transplant approach. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Prophylactic Modified Donor Lymphocyte Infusion after Allogeneic Peripheral Blood Stem Cell Transplantation for Very High-Risk Hematological Malignancies: Low Incidence of Relapse without Increasing the Risk of Graft-Versus-Host Disease

Introduction The prognosis of patients with very high-risk hematologic malignancies who have relapsed/refractory diseases or carrying very poor-risk gene mutations were dismal even after allogeneic hematopoietic stem cell transplantation. Donor lymphocyte infusion (DLI) is a promising prophylactic strategy for reducing relapse after transplant. However, DLI-associated graft-versus-host disease (GVHD) and non-relapse mortality (NRM) were still concerned, especially after allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Therefore, prophylactic DLI should be safe with tolerable DLI-associated GVHD and NRM except for its anti-leukemia effect. To evaluate the safety and efficacy of prophylactic DLI for the very high-risk hematologic malignancies after allo-PBSCT, we performed a cohort study in 160 consecutive patients with hematological malignancies who received unmanipulated allo-PBSCT. DLI procedure was modified to use G-CSF mobilized peripheral progenitors instead of steady state lymphocytes and 4 to 6 weeks of immunosuppressant for prevention of DLI-associated GVHD. The outcomes of those very high-risk patients (group A: DLI group; group B: non-DLI group) and the patients without the very high-risk features (group C) who were not planned for prophylactic DLI were compared.Patients and Methods The underlying diseases consist of acute myeloid leukemia (n = 78), myelodysplastic syndrome (n = 22), acute lymphoblastic leukemia/lymphoma (n = 45), chronic myeloid leukemia (n = 7), non-Hodgkin's lymphoma (n = 7), and plasma cell leukemia (n = 1). Sixty five patients (41.2%) received allo-PBSCT from HLA-matched sibling donors, 7 patients (4.4%) from matched unrelated donors, and 87 patients (54.4%) from haploidentical donors (Table 1). The very high-risk features were defined as 1) disease in non-remission state at time of transplant; 2) acute leukemia achieving complete remission (CR1) with 3 or more cycles of induction chemotherapy; 3) leukemia in CR1/CR2 carrying TP53, TET2 or DNMT3A gene mutation. Patients in CR with FLT3/ITD or BCR/ABL T315I gene mutation were enrolled due to the unavailability of effective targeted drugs. Prophylactic modified DLI was planned at 30 to 60 days post-transplant for all very high-risk patients with the absence of GVHD. The infusion was G-CSF mobilized peripheral progenitors from cryopreserved cell aliquots of the original graft. The trough concentration of CSA was maintained at 180 to 250 ng/mL for at least 4 to 6 weeks post-DLI and then discontinued within 2 weeks when no GVHD occurred. All the patients were followed-up for a median of 11.1 (0.5 - 29.7) months after transplant.Results Prophylactic DLI was administered for 29 very high-risk patients (group A) at a median of 63 (25 - 176) days after transplant. The median numbers of mononuclear cells and CD3+ lymphocytes infused were 0.7 (0.1 - 1.4) × 108/kg and 18.5 (5.4 - 69.2) × 106/kg with a single dose. Nineteen patients (39.6%) with very high-risk features did not receive prophylactic DLI (group B) for the reasons of early relapse (n = 8), occurrence of GVHD (n = 8), and uncontrolled infections (n = 3). The cumulative incidence (CI) of grade II-IV acute GVHD at day 100 after transplant was 33.2% in group A, 38.0% in group B (p= 0.318), and 28.2% in group C (p= 0.746). The 2-year CI of chronic GVHD was 29.9% in group A, 15.8% in group B (p= 0.428), and 54.6% in group C (p= 0.255). The 2-year CI of relapse was 54.6% in group A, which was significantly lower than that in group B (68.4%, p= 0.019). The relapse-free survival in group A was superior to that in group B (37.3% vs . 24.6%, p = 0.032). In the very high-risk group of patients (group A and B), prophylactic DLI was correlated with a lower risk of relapse (p= 0.043, hazard ratio = 0.45). The 2-year CI of NRM in group A was not significantly different from that in group B (22.4% vs . 15.8%, p= 0.461) or group C (22.4% vs . 23.2%, p= 0.949). In addition, there was no significant difference in overall survival between group A and group B (48.6% vs . 35.1%, p = 0.134). The 6-month CI of CMV/EBV reactivations in group A was not significantly different from that in group B (p= 0.107 and p= 0.668) or group C (p= 0.130 and p= 0.596).Conclusions This study showed that the prophylactic DLI after unmanipulated allo-PBSCT was well tolerated and effective for the patients with very high-risk hematologic malignancies in decreasing relapse without increasing the risks of GVHD and NRM. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Differential Impact of Conditioning Intensity on Post-Transplant Outcome of FLT3 -Mutated and FLT3 Wild Type AML in First Remission, a Report from Taiwan Bone Marrow Transplant Registry (TBMTR)

AML with FLT3 -internal tandem duplication mutation (FLT3-ITD) has a very high relapse rate when patients were treated with chemotherapy alone. Allogeneic hematopoietic stem cell transplantation (HSCT) as soon as possible once remission is achieved is generally recommended. Nevertheless, the best conditioning regimen, specifically the myeloablative (MAC) or reduced intensity conditioning (RIC), for FLT3-ITD AML remains unknown. Of the two largest series reported so far, vast majority of the patients received myeloablative regimen (100% in EBMT report, 87% in CIBMTR report). In this study, we utilize the Taiwan Bone Marrow Transplant Registry (TBMTR) database to analyze the impact of conditioning intensity on the post-transplant outcome of FLT3 -mutated and FLT3 wild type AML.TBMTR is a research collaboration affiliated to the Taiwan Society of Blood and Bone Marrow Transplantation. It comprises all the 14 transplantation centers in Taiwan that contribute detailed information on HSCT. In this study, only adults aged ≥ 18 years with a diagnosis of de novo AML who received allogeneic peripheral blood stem cell transplantation (PBSCT) at the first complete remission (CR1) and with known FLT-ITD mutation status in the registry were included. Patient characteristics and transplant outcome following MAC or RIC allogeneic PBSCT were compared. Kaplan-Meier estimates were used to calculate the probability of LFS and overall survival (OS). Cumulative incidence of relapse and non-relapse mortality (NRM) was calculated from the time of transplant to the time of event. NRM was considered a competing risk for relapse and vice versa. Multivariable analyses for LFS and OS were performed using Cox proportional hazards model.146 patients who met the eligibility criteria were enrolled for analysis. The median follow-up of survivors was 21 months (range, 1-73 months). Of the 146 patients, 49 (33.6%) were positive and 97 (66.4%) were negative for FLT3-ITD mutation. 32.7% and 35.1% of FLT3-ITD mutated and FLT3 WT AML received RIC regimen respectively. FLT3-ITD mutated patients had significantly higher WBC count (51.7 x 109/L) and more normal (64.9%) karyotype at diagnosis comparing to patients without FLT3 mutation (11.8 x 109/L WBC count and 42% normal karyotype). Patients who received RIC regimen were significantly older than patients who received MAC regimen (53.196±12.107 vs 38.327±11.788, p<0.001, for FLT3-ITD mutated AML; 52.084±12.533 vs 39.181±10.704, p<0.001, for FLT3 WT AML).In multivariable analysis, FLT3 mutation status did not negatively impact the transplant outcome in term of both overall survival (OS) and leukemia free survival (LFS). However, RIC regimen is associated with a significant poor LFS (HR 1.754, p=0.0476) and higher relapse rate (HR 2.184, p=0.015). The impact of conditioning intensity is even more prominent in patients of FLT3 WT AML (Figure 1, left, p=0.0468 for LFS, log rank test). For FLT3-ITD mutated AML, the LFS and relapse rate were almost the same after either MAC or RIC conditioning (Figure 1, right, p=0.768 for LFS, log rank test). For NRM and cumulative incidence of acute and chronic GVHD, the differential impact of conditioning intensity was not seen in FLT3-ITD mutated AML and FLT3 WT AML.In conclusion, conditioning intensity has a differential impact on post-transplant outcome of FLT3-ITD mutated AML and FLT3 WT AML. Reduced intensity conditioning is associated with a lower LFS and higher relapse rate for FLT3 WT AML. For patients of FLT3-ITD mutated AML, RIC is just as good as MAC, even though patients who received RIC were almost 15 years older than patients who received MAC. RIC allogeneic HSCT should be a viable option for elderly or unfit AML with FLT3-ITD mutation. [Display omitted] DisclosuresYao:Celgene International Sàrl: Research Funding. Tang:Celgene International Sàrl: Research Funding.