Venetoclax/FluBu2 RIC transplant followed by all-oral venetoclax/decitabine maintenance for poor-risk MDS/AML.

Outcome of Patients Undergoing Hematopoietic Cell Transplantation for TP53-Mutated Acute Leukemias and MDS: Effect of Conditioning and GvHD Prophylaxis Regimens Intensity

Challenges of Maintenance Tyrosine Kinase Inhibitor Therapy after Allogeneic Hematopoietic Cell Transplantation in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

The limited impact of preexisting rheumatologic diseases on outcomes after allogeneic hematopoietic stem cell transplantation: A nationwide Propensity–Matched analysis

Risk of Relapse Post Reduced Intensity Conditioning Allogeneic Stem Cell Transplant in Patients with High-Risk Myeloid Neoplasms Based on Ptcy Vs TAC/MTX Gvhd Prophylaxis

Monocytes Matter: Impact of Monocyte Recovery on Allogeneic Hematopoietic Stem Cell Transplant Outcomes with Post-Transplantation Cyclophosphamide As Graft Versus Host Disease Prophylaxis

Factors influencing outcomes in therapy-related myeloid neoplasms following allogeneic hematopoietic stem cell transplantation

T-Cell Depletion Improves the Composite End Point Graft-Versus-Host Disease-Free, Relapse-Free Survival after Allogeneic Hematopoietic Stem Cell Transplantation

Post-transplant cyclophosphamide vs tacrolimus/methotrexate: Improved GRFS, reduced NRM, and less severe GVHD in myeloablative HLA-matched allogeneic transplantation

Graft-versus-Host Disease: State of the Science

Abstract 2013 Purpose:The introduction of reduced intensity conditioning (RIC) regimens has allowed performing allogeneic hematopoietic cell transplantation (HSCT) in previously discarded old or unfit patients. In this fragile population, non-relapse mortality (NRM) has been dramatically reduced, making the post-transplant disease control the remaining challenge. Over the last years, we have tuned the chemotherapy dose intensity of a busulfan based RIC regimen with the aim to better control disease while retaining a low toxicity profile. In this perspective, we retrospectively analyzed a cohort of patients with myeloid malignancies treated identically in two French centers. Patients and methods:From 2005 to 2010 in Marseille and Nantes we transplanted 165 patients (median age: 56.8 years (range:18–71); males: 83, females: 82) presenting AML (N=124) or MDS (N=41) following a similar conditioning regimen but for the dose of busulfan (Bu): 1/Fludarabine (30 mg/m2/day over 5 days) 2/, rabbit anti-thymocyte-globulins (r-ATG) (2.5mg/kg/day over 2 days) and 3/ i.v. or oral Busulfan (Bu) (130 mg/m2/day or 3.2 mg/kg respectively over 2 to 4 days) (table 1). Ciclosporin A was given as post graft immunosuppression. Initially higher Bu doses were proposed to patients under the age of 55, without comorbidities and with higher risk diseases. These indications were progressively extended over time when it became evident that toxicity was not dramatically increased. Results:With a median follow up of 20.7 months for surviving patients, 2 year overall survival (OS) and progression free survival (PFS) were 59.6% (95% CI: 51.8–68.6) and 54.9% (95% CI: 47–64) respectively. Cumulative incidence of grade 2–4 and 3–4 acute graft-versus-host diseases (aGvhD) at day 100 was 19.4% and 7.9% respectively. Cumulative incidence of chronic GvhD (all grades) and extensive chronic GvhD was 25% and 14.4% at 1 year post transplantation respectively. NRM was 11.7 and 15.4% at 12 and 24 months. Cumulative incidence of relapse (CIR) was 24% and 29.7% at 1 and 2 years.Overall neither the patient age, nor the donor type or the dose of Bu influenced significantly OS, PFS or CIR in the whole cohort. Surprisingly, NRM was lower after 3 or 4 days Bu conditioning regimen (3.6% vs 21.3%, p=0.009).AML patients transplanted in 1st complete remission (n=93): those patients had 2-year OS and PFS of 63.4% (95% CI: 53.3–75.3) and 60.9% (95%CI: 50.8–72.9) respectively. Two-year OS reached 66.4% (95%CI: 56.4–81.8) for patients with favorable/intermediate karyotype and 50.5% (95%CI: 33–77.3) for unfavorable, p=0.08. Patients with favorable or intermediate karyotype tend to have a better 2-year PFS (63.8%, 95%CI: 52.2–78.1) than unfavorable karyotype (52%, 95%CI: 34.5–78.3), p=0.2.Patients under the age of 55 (n=76): this population presents overall a better outcome than older (OS: 63.9 (CI: 52.7–74.4) vs 56% (CI: 45.6–68.7), p=0.2, PFS: 60.5 (49.7–73.8) vs 50.4% (CI: 40–63.5), p=0.2, NRM: 9.4 vs 20.3%, p=0.07). In addition higher doses of Bu improved OS (77.5% vs 47.9%, p=0.058), PFS (71.6 vs 46.4%, p=0.1), without increase of NRM (2.2% vs 18.7%, p=0.03). Conclusion:This conditioning regimen using Fludarabin, Bu and r-ATG can result in good OS and PFS probabilities in myeloid malignancies. Given the patient population characteristics', the NRM can be considered as low. Interestingly enough even if patients who received 3 or 4 days of Busulfan were younger and had less comorbid conditions, which is a bias, they had a lower NRM than those who received only 2 days of bu. In younger patients higher doses of Bu seem to be associated with better prognosis. These encouraging results led us setting up a prospective study comparing different doses of Bu in poor risk myeloid malignancies undergoing HLA identical allo HSCT and ineligible for standard double alkylating agent or high dose TBI based conditioning.Table 1Patients and transplant's characteristics.Patients characteristicsN%centerMarseille10865,5Nantes5734,5gendermale8350,3female8249,7age at transplantation< 55 years7646,1≥55 years8953,9diagnosisAML12475,2MDS4124,8karyotype (AML)Favorable118,9Intermediate8165,3Unfavorable3225,8NR1disease statusAML CR19356,4AML CR> =22313,9AML refractory84,8MDS CR106,1MDS PR/SD3118,8transplants' characteristicsdonor typeMRD9255,8MUD3420,6MMUD148,5cell sourcePBSC15795,2BM84,8Day nb of Bx/BU210664,233521,242414,5 Disclosures:No relevant conflicts of interest to declare.

Survival Trends in Multiple Myeloma after Autologous Hematopoietic Stem Cell Transplantation

Favorable Survival Outcomes in AML Patients Undergoing Allogeneic Hematopoietic Cell Transplant with Fludarabine/Melphalan-Conditioning with Tacrolimus/Sirolimus-Based Gvhd Prophylaxis

Primary Cancer Matters in Therapy-related Myeloid Neoplasm Patients Receiving Allogeneic Hematopoietic Cell Transplantation: A Study From the Chronic Malignancies Working Party of the EBMT

Size Does Not Always Matter: Limited Impact of Donor-recipient Weight Difference on Outcomes of Adult Allogeneic Peripheral Blood Stem Cell Hematopoietic Cell Transplantation.

Venetoclax-Based Therapy before Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia