Post-transplant Cy Research Articles

Comparison of Two Reduced Intensity Conditioning Regimens (Baltimore with Clofarabine vs Thiotepa-Busulfan-Fludarabine) in Adults Receiving Peripheral Blood Stem Cell Haploidentical Transplantation for Myeloid Malignancies: A Retrospective Study of the SFGM-TC

Background: Haploidentical transplantation (haploT) has become a routine practice in many centers but the optimal conditioning regimen has yet to be determined. Indeed, the historic Baltimore reduced intensity conditioning (RIC) regimen has been associated with poor outcomes in myeloid malignancies. Two alternative RIC regimens have recently demonstrated promising results in this setting. One of them replaces fludarabine with second-generation nucleoside analogue clofarabine (Clo-Baltimore regimen [CloB], Chevallier et al., Oncotarget 2018) and the other combines thiotepa-busulfan-fludarabine (TBF, Duléry et al., BBMT 2019). Here we compared outcomes in order to determine if one of these two regimens was superior for the treatment of myeloid malignancies. Methods: This was a multicenter retrospective study conducted by the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC). All consecutive adults having received a haploT after a CloB or a TBF RIC regimen for a myeloid malignancy between September 2013 and May 2023 were eligible. Patients data were extracted from the PROMISE database. CloB consisted of clofarabine 30 mg/m²/day (d) 5 d, cyclophosphamide (Cy) 14.5mg/kg/d 2 d, and 2-Gy TBI on d-2. TBF consisted of thiotepa 5mg/kg 1 d, busulfan 3.2 mg/kg 2 d, a fludarabine total dose of 120 to 150 mg/m². Graft-versus-host disease (GVHD) prophylaxis consisted of post-transplant Cy (2 doses of 50mg/kg), followed by cyclosporine A and mycophenolate mofetil starting on d+5. Some patients received antithymocyte globulin (ATG) 2.5mg/kg/d on d-2. Graft source was exclusively peripheral blood stem cells (PBSC). To minimize bias between the CloB and the TBF groups, a propensity score matching (PSM) was constructed using a logistic regression model that included age, donor and recipient sex, hematopoietic cell transplantation-specific comorbidity index (HCT-CI), disease, cytogenetic risk (European LeukemiaNet [ELN] 2022), previous transplant, use of ATG, and cytomegalovirus (CMV) status, with the nearest-neighbor algorithm, and strict matching of key factors. Matched groups were then compared for time to engraftment (absolute neutrophil count > 0.5 x 10 9/L) and platelet (PLT) recuperation (>50 x 10 9/L), overall survival (OS), progression-free survival (PFS), GVHD-free, progression-free survival (GRFS), non-relapse mortality (NRM), and incidences of relapse as well as acute and chronic GVHD. Results: A total of 329 patients from 25 centers were included, 267 (81%) receiving TBF and 62 (19%) CloB. After PSM, 51 patients remained in each group, with comparable baseline characteristics except for the proportion of previous allotransplants ( Table). Median age was 60 years, and median HCT-CI score was 2. Main diagnoses comprised acute myeloblastic leukemia (AML, n=72 [71%]), including 42% with adverse genetic risk, and myelodysplastic syndrome (MDS, n=22 [22%]), including 25% with high or very high Revised International Prognostic Scoring System (R-IPSS). Thirty-eight (37%) patients received ATG. Time to engraftment was equivalent after both TBF and CloB (19 d vs 19.5 d, respectively, p=0.70), but TBF patients achieved PLT recuperation faster (27 d vs 31 d, p=0.03). Median follow-up was 24 months. Two-year OS, PFS and GRFS were 55% vs 60% (p=0.19), 52% vs 60% (p=0.25), and 37% vs 50% (p=0.15) for TBF and CloB patients, respectively. No differences were observed in terms of grade 3-4 acute GVHD at 3 months (18 vs 20%, p=0.86) nor two-year extensive chronic GVHD (16% vs 8.3%, p=0.25). However, two-year NRM was significantly higher after TBF (41% vs 16%, p=0.003), while relapse incidence was lower (7.1% vs 24%, p=0.02, Figure). In multivariate analysis, CloB was associated with a lower risk of NRM (hazard ratio [HR] 0.31, 95%CI: 0.1-0.7, p=0.008) and a higher risk of relapse (HR 4.03, 95%CI: 1.2-13.9, p=0.03). Finally, in patients aged >60y, two-year OS was significantly lower for those receiving TBF conditioning (39% vs 61%, p=0.02, Figure) due to higher NRM (56% vs 23%, p=0.005). Conclusions: In this retrospective study, a TBF RIC regimen used for PBSC haploT in adults with myeloid malignancies appeared substantially more toxic than a CloB RIC regimen. However, its enhanced anti-leukemic effect suggests that it should be offered to younger patients with no comorbidities or to those with high-risk disease. Conversely, CloB should be proposed for older or frail patients.

Haploidentical Hematopoietic Cell Transplant with Post-Transplant Cyclophosphamide Expedites Donor-Derived Immune Reconstitution in a Pediatric Severe Aplastic Anemia Cohort

Severe aplastic anemia (SAA) is a life-threatening, idiopathic process involving the immune-mediated destruction of hematopoietic stem cells. Treatment involves immunosuppressive therapy (IST) and/or allogeneic hematopoietic cell transplantation (HCT). The latter has recently been optimized with use of a post-transplant cyclophosphamide (PTCy) based graft-versus-host disease (GvHD) platform, permitting successful HCT with only half-HLA-matched haploidentical donors. In pediatrics, this platform results in >90% overall survival with low rates of GvHD and graft failure. However, reports on donor chimerism and immune reconstitution are limited. We hypothesized that a PTCy platform would expedite CD3 donor engraftment and CD4 T cell recovery. In a phase III clinical trial, we treated three cohorts of pediatric (age </=25 years) patients with SAA requiring alloHCT: MUD, MSD, and HAPLO. The MUD cohort included n=15 recipients of 7-8/8 HLA-matched unrelated donor grafts (n=5 7/8, n=10 8/8) with median age 14 years (range 2-17 years), following cyclophosphamide (Cy) 50 mg/kg, fludarabine (Flu) 200 mg/m 2, rabbit anti-thymocyte globulin (rATG) 9 mg/kg total dose rabbit and low dose total body irradiation (TBI) at 200 cGy. The MSD cohort included n=9 recipients of 8/8 HLA-matched sibling donor grafts with median age 15 years (range 12-24 years), following Cy 200 mg/kg and 9 mg/kg rATG. The HAPLO cohort included n=4 recipients of 4/8 HLA-matched related donor grafts with median age 8.5 years (range 2-21 years) following Cy 29 mg/kg, Flu 150 mg/m 2, 9 mg/kg rATG, and low dose TBI at 200 cGy. GvHD prophylaxis consisted of 30 days of mycophenolate mofetil, and 100 days of a calcineurin inhibitor (followed by an 8-10 week taper), with the HAPLO cohort additionally receiving post-transplant Cy (PTCy) 50 mg/kg/day on days +3 and +4. Peripheral blood lymphocyte counts and peripheral blood and bone marrow donor chimerism were evaluated on days +100, +180 and +365. Recipient characteristics were largely equivalent between cohorts, with 43% receiving IST prior to HCT. Clonality was overrepresented in the HAPLO cohort (2 of 4, 1 with monosomy 7 myelodysplastic syndrome and 1 with a large PNH clone), with only 2 of 15 in the MUD and none in the MSD cohorts. Active controlled infections at the time of HCT were additionally overrepresented in the HAPLO cohort, with disseminated pseudomonas in 1. The MUD cohort had 1 with Rhizopus invasive sinusitis (none in the MSD cohort). Achievement of neutrophil engraftment was statistically significantly delayed in the HAPLO cohort at a median of 17 days compared to 12 for MSD and 14 for MUD, p=0.004), however there were no episodes of primary or secondary graft failure. With only a single late death from intracranial hemorrhage in the MUD cohort, OS was equivalent at 2 years (100% in MSD and HAPLO cohorts, 93.3% in MUD). GvHD rates were low with only 1 (MUD) experiencing grade II acute GvHD, and 1 (MUD) experiencing mild chronic GvHD. Immune reconstitution varied by cohort with statistically significantly greater CD3 peripheral blood donor chimerism (p<0.001) as well as CD4 (p=0.04) and CD8 (p=0.03) T cell counts over time for the HAPLO recipients (CD3 chimerism in Fig 1, CD4 count in Fig 2; 2-way ANOVA fixed effects model). Considering a CD4 >200 cell/uL as clinically meaningful, we assessed the proportion of each cohort achieving this milestone at each timepoint. While each cohort had an increase in proportion achieving CD4>200 over time, the HAPLO cohort reached 50% with CD4 >200 at day +100, compared to 11% MUD and 0% MSD (p=0.09). At day +180, the proportion with CD4 >200 were 36% MUD, 25% MSD and 75% HAPLO (1 yr: 90% MUD, 100% MSD and HAPLO). Donor availability remains a challenge to successful transplant for patients with SAA, and haploidentical matches overcome donor limited accessibility. PTCy as GvHD prophylaxis is associated with low incidences of graft failure and severe GvHD. While PTCy might be anticipated to inhibit donor T cells and immune reconstitution, our data, albeit limited by small cohorts, demonstrates superior and more efficient CD3 donor engraftment and CD4 T cell count recovery following HAPLO HCT with PTCy compared to non-PTCy based MUD and MSD cohorts.

Low-dose post-transplant cyclophosphamide with G-CSF/ATG based haploidentical protocol provides favorable outcomes for SAA patients.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT), as one of the life-saving treatments for severe aplastic anemia (SAA), is widely used because of its great donor availability. Over decades, granulocyte colony-stimulating factor (G-CSF)/antithymocyte globulin (ATG)-based protocol (the so-called Beijing Protocol) has achieved favorable engraftment and survival outcomes. In this study, we modified the conventional Beijing Protocol: the full-dose Cyclophosphamide (Cy) (200 mg/kg in total) was divided into 42.75 mg/kg Cy on day -5 to day -2 and Low dose post-transplant Cy (PTCy) (14.5 mg/kg on days +3 and +4), hoping to reduce the incidence of severe acute graft-versus-host disease (aGVHD) and to guarantee successful and stable engraftment. Here we retrospectively reported and analyzed the data of first 17 patients with SAA who had received haplo-HSCT using this novel regimen between August 2020 and August 2022. The median follow-up was 522 days (range, 138-859 days). No patient developed primary graft failure. Four (23.5%) patients developed grade II bladder toxicity, two (11.8%) patients developed grade II cardiotoxicity. All patients achieved neutrophil and platelet engraftment at median times of 12 days (range, 11-20 days) and14 days (range, 8-36 days). During our follow-up, no patients developed grade III-IV aGVHD. The cumulative incidence of grade II and grade I aGVHD at 100 days was 23.5% (95% CI, 6.8%-49.9%) and 47.1% (95% CI, 23.0%-72.2%). Three patients (17.6%) developed chronic GVHD of skin, mouth, and eyes and all of which were mild. All patients are alive by the end of the follow-up, with a failure-free survival of 100%, which was defined as survival without treatment failures, such as death, graft failure, or relapse rate. The rate of cytomegalovirus (CMV) reactivation was 82.4% (95% CI, 64.3%-100%). The rate of Epstein-Barr virus (EBV) reactivation was 17.6% (95% CI, 3.8%-43.4%). No CMV disease and post-transplantation lymphoproliferative disorder (PTLD) occurred among these patients. In conclusion, the encouraging results of prolonged survival outcomes and reduced incidence of GVHD suggest promising effect of this novel regimen in haplo-HSCT for patients with SAA. Larger-sample prospective clinical trials are needed to confirm the effectiveness of this regimen.

Impact of Conditioning Regimen and Graft-versus-Host Disease Prophylaxis on The Outcome of Haploidentical Peripheral Blood Stem Cell Transplantation for High-Risk Severe Aplastic Anemia in Children and Young Adults: A Report from the Pediatric Severe Aplastic Anemia Consortium of India

Allogenic hematopoietic cell transplantation (HCT) is the best curative approach for patients with severe aplastic anemia (SAA). The outcomes of HCT from haploidentical family donors (HFDs) have improved, making it a feasible option for patients lacking an HLA-identical donor. However, data on HFD-HCT for younger patients with SAA is sparse. In this multicenter retrospective study, we evaluated the outcomes of 79 patients undergoing HFD-HCT for SAA. All the patients were heavily pretransfused, the median time to HCT was >12 months, and 67% had failed previous therapies. Conditioning was based on fludarabine (Flu)-cyclophosphamide (Cy)-antithymocyte globulin (ATG)/total body irradiation (TBI) with or without thiotepa/melphalan (TT/Mel). Post-transplantation Cy (PTCy) and calcineurin inhibitors (CNIs)/sirolimus were used as graft-versus-host disease (GVHD) prophylaxis with or without abatacept. The rate of primary graft failure (PGF) was 16.43% overall, lower in patients conditioned with TT/Mel. The incidences of acute and chronic GVHD were 26.4% and 18.9%, respectively. At a median follow-up of 48 months, the overall survival (OS) and event-free survival (EFS) were 61.6% and 58.1%, respectively. Both OS and EFS were better in the TT/Mel recipients and with abatacept as GVHD prophylaxis. On multivariate analysis, the use of abatacept was found to favorably impact the outcome variables, including GVHD and EFS. Our study suggests that PTCy-based HFD-HCT is a reasonable option for young patients with high-risk SAA, in whom optimization of conditioning and GVHD prophylaxis might further improve outcomes.

Total marrow irradiation (TMI): Addressing an unmet need in hematopoietic cell transplantation - a single institution experience review.

PurposeTMI utilizes IMRT to deliver organ sparing targeted radiotherapy in patients undergoing hematopoietic cell transplantation (HCT). TMI addresses an unmet need, specifically patients with refractory or relapsed (R/R) hematologic malignancies who have poor outcomes with standard HCT regimens and where attempts to improve outcomes by adding or dose escalating TBI are not possible due to increased toxicities. Over 500 patients have received TMI at this center. This review summarizes this experience including planning and delivery, clinical results, and future directions.MethodsPatients were treated on prospective allogeneic HCT trials using helical tomographic or VMAT IMRT delivery. Target structures included the bone/marrow only (TMI), or the addition of lymph nodes, and spleen (total marrow and lymphoid irradiation, TMLI). Total dose ranged from 12 to 20 Gy at 1.5-2.0 Gy fractions twice daily.ResultsTrials demonstrate engraftment in all patients and a low incidence of radiation related toxicities and extramedullary relapses. In R/R acute leukemia TMLI 20 Gy, etoposide, and cyclophosphamide (Cy) results in a 1-year non-relapse mortality (NRM) rate of 6% and 2-year overall survival (OS) of 48%; TMLI 12 Gy added to fludarabine (flu) and melphalan (mel) in older patients (≥ 60 years old) results in a NRM rate of 33% comparable to flu/mel alone, and 5-year OS of 42%; and TMLI 20 Gy/flu/Cy and post-transplant Cy (PTCy) in haplo-identical HCT results in a 2-year NRM rate of 13% and 1-year OS of 83%. In AML in complete remission, TMLI 20 Gy and PTCy results in 2-year NRM, OS, and GVHD free/relapse-free survival (GRFS) rates of 0%, 86·7%, and 59.3%, respectively.ConclusionTMI/TMLI shows significant promise, low NRM rates, the ability to offer myeloablative radiation containing regimens to older patients, the ability to dose escalate, and response and survival rates that compare favorably to published results. Collaboration between radiation oncology and hematology is key to successful implementation. TMI/TMLI represents a paradigm shift from TBI towards novel strategies to integrate a safer and more effective target-specific radiation therapy into HCT conditioning beyond what is possible with TBI and will help expand and redefine the role of radiotherapy in HCT.

THE POLYOMAVIRUS HEMORRHAGIC CYSTITIS TREATMENT PUZZLE: A SUCCESS CASE AFTER HEMATOPOIETIC CELL TRANSPLANTATION

BK virus (BKV)-hemorrhagic cystitis (HC) is a well-known complication of hematopoietic stem cell transplantation (HSCT), and contributes to significant morbidity. We report on and discuss the management of a patient with BK viremia, whose post-HSCT course was complicated by severe BKV-HC, combined with grade IV skin and gut graft vs host disease (GVHD). A 15 year-old boy diagnosed with leukemia underwent an HSCT with his mother as the haploidentical donor. Graft source was bone marrow, with TNC/kg 4.4 × 10*8/kg. Neutrophil engraftment was achieved at day +16; chimerism demonstrated 100% donor cells. Myeloablative conditioning consisted of cclophosphamide (Cy) 50 mg/kg x 2 days (days -5 to -4) and total body irradiation 12 Gy on days -3 to -1. GVHD prophylaxis consisted of post-transplant Cy on days +3 and + 4 along with mycophenolate mofetil x 30 days and cyclosporin. His transplant course was complicated by cytomegalovirus (CMV) infection and grade II skin GVHD. He was discharged on day +20 and readmitted on day +39 with grade IV skin GVHD and transferred to the intensive care unit. Immunosuppressive medications (Ruxolitinib with IV methylprednisolone) were started, and his symptoms started to improve. However, he developed severe lower urinary tract symptoms and hematuria with frequent passage of clots on Day +65. A diagnosis of grade III hemorrhagic cystitis (HC) was made. Quantitative PCR from serum (600 copies/mL) as well as from urine came positive for BK polyomavirus, Cidofovir was started and immunosuppression reduced. Continuous bladder irrigation was initiated without significant improvement. On day +86, a cystoscopy was done for clot evacuation. As he was unstable on day+105 a transvesical catheterization was performed, with opening of the bladder, matured to the skin, with compression of the mucosa by surgical compresses for bleeding control, which was removed after 48 hours. D+113 persisted with active bleeding, requiring re-approach, and a 3 way Foley catheter was inserted. He received daily hyperbaric sessions for 2 months. Progressive improvement of hematuria was seen, and a bladder ultrasound was performed for control, on day+123, with a slightly distended bladder, without signs of bleeding. On day+147, the cystostomy was closed and no new episodes of bleeding occurred. The patient was discharged from the ICU after 4 months, and all viral PCRs were negative, chronic GVHD was well controlled with reduced immunosuppression and absence of hematuria. Patient is alive with sustained donor engraftment and excellent hematopoietic function at 10 months post-HSCT. Treatment of BKV associated HC is currently controversial. This case highlights the importance of balancing immunosuppression and infection treatment post-HSCT. It must be emphasized that at present no standard guidelines are drafted regarding treatment of BK virus related HC.

Evaluation of the risk factors for BK virus-associated hemorrhagic cystitis in pediatric bone marrow transplantation patients: Does post-transplantation cyclophosphamide increase the frequency?

BKV-HC is one of the most significant complications of HSCT. This retrospective study aimed to determine the frequency of BKV-HC in pediatric patients undergoing HSCT, detect the associated risk factors for the development of BKV-HC, and explore the effects of post-transplantation Cy use. Three hundred twenty-seven patients (girls: 121, boys: 206) were analyzed according to sex, conditioning regimen, transplantation type, donor relatedness, stem cell source, the presence and grade of aGVHD, CMV co-existence, and Cy use. Multivariate analysis confirmed the prognostic importance of age (OR: 4.865), TBI use, the presence of aGVHD (OR: 2.794), CMV coinfection (OR: 2.261), and Cy use (OR: 27.353). A statistically significant difference was found between the mean BKV-HC follow-up times compared with post-transplantation Cy intake (p < .001). The BKV-HC rate increased as the number of risk factors of the patient increased. BKV-HC is an essential complication of HSCT primarily associated with Cy use, the presence of aGVHD, and donor relatedness. The present study shows that the use of Cy in the post-transplantation period further increases BKV-HC risk in pediatric patients, regardless of dose.

Myeloproliferative neoplasms – a global view

Myeloproliferative neoplasms – a global view

Haploidentical Stem Cell Transplantation Can be Fully Conducted on an Outpatient Basis

IntroductionHaploidentical hematopoietic stem cell transplantation (haplo-SCT) has become an acceptable approach for many patients; however, the suitability of this procedure and outcomes regarding efficacy and safety remain unclear. Here we present a single-center experience using a conditioning regimen based on cyclophosphamide and fludarabine under outpatient conditions.Methods:Retrospective study evaluating the performance of haplo-SCT in a single center. The conditioning regimen was fludarabine 50 mg on days -6 through -4, cyclophosphamide (Cy) 500 mg/m 2 on days -7 to -4 and tacrolimus 1000 mg and post-transplant Cy (50 mg/kg) on days +3 and +4 (Figure 1). Donor cell collection was accomplished through apheresis in all patients and fresh cells were administered on same day of collection. All the procedures were started on an outpatient basis. Overall survival was defined as mortality for any reason, starting to count from the day of transplantation to the date of death. The survival function was calculated according to the Kaplan-Meier estimation method. All patients signed a consent to participate after a thorough interview and the study protocol was approved by Clínica Ruiz IRB.Results:We grafted 20 patients, (14 adults and 6 children) with haploidentical cells and found that in 11 cases (55%), the full procedure could be completed totally as outpatients; the diagnosis of the grafted patients were: 10 acute lymphoblastic leukemia, 3 acute myelogenous leukemia, 3 paroxysmal nocturnal hemoglobinuria, and one each non-Hodgkin´s lymphoma, Blackfan-Diamond syndrome and multiple myeloma. Nine patients (3 children and 6 adults) were admitted to the hospital after completing the conditioning, 1 to 8 days after day 0: the causes for admission were neutropenic fever (5 cases), cytokine-release syndrome (3 cases), and intraabdominal abscess (1 case). Patients remained in the hospital for a median of 9 days. Four patients failed to engraft and recovered endogenous hematopoiesis and acute graft versus host-disease developed in 5 of 16 engrafted patients; two patients relapsed after the haplo-SCT. The transplant-related mortality was 35%, whereas the 2-year overall survival (OS) was 37.5% (Figure 2); the causes of the 7 deaths were: Four granulocytopenic sepsis, 2 graft-versus-host disease and one multiple organ failure.ConclusionsHaplo-SCT procedures can be conducted safely and effectively on an outpatient basis; however, questions remain regarding the selection of patients and managing of complications, especially in outpatient conditions in which full and timely availability of specialized care could be the pivotal factor to improve short-term outcomes. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Post Transplantation Cyclophosphamide Improves Outcome of Autologous Hematopoietic Stem Cell Transplantation in Animal Model of Multiple Sclerosis

Experimental allergic encephalomyelitis (EAE) is the animal model of multiple sclerosis (MS). Autologous hematopoietic stem cell transplantation (AHSCT) has recently been recognized as the standard treatment for MS. The aim of our experiment was to investigate the effect of AHSCT with the addition of low-dose post-transplantation cyclophosphamide (Cy) on EAE in rats. Low dose post-transplantation Cy is used in haploidentical HSCT to reduce the risk of graft versus host disease. We hypothesized that it could bring additional benefit in autologous HSCT in autoimmune diseases. Rats with evoked EAE were treated with high dose (125 mg/kg) Cy, followed by AHSCT or high dose (125 mg/kg) Cy followed by AHSCT followed by low dose (20 mg/kg) Cy in two-time schedules—with the therapy applied during the pre-symptomatic or symptomatic phase of the disease. Both AHSCT and AHSCT with post-transplantation Cy in accordance with both time schedules reduce the intensity of the inflammatory response in the CNS, in comparison with non-treated EAE rats. The reduction of clinical symptoms was present in all AHSCT treatment protocols, however, it was significantly stronger when post-transplantation Cy was given during the symptomatic phase of the disease. AHSCT with the addition of post HSCT low dose Cy improved the results of AHSCT by not only reducing the intensity of inflammation in the CNS but also by significantly reducing the clinical symptoms in treated animals when compared to AHSCT alone. We provide an experimental rationale that the addition of post-transplantation Cy may improve the outcome of HSCT in MS.Graphic

Reduced Relapse and Improved Survival in Chemosensitive Hodgkin Lymphoma Patients Undergoing Haploidentical Related Donor Compared to HLA-Identical Donor Transplantation

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents a potential curative option for patients with relapsed or refractory Hodgkin's lymphoma (RR HL).Allo-HSCT from haploidentical donor (haplo-HSCT), when HLA identical donor is not available, is considered a good alternative. Using haploidentical donors, the immunological activity against HL seems to be particularly high. In this retrospective study, we analysed the results obtained using HLAid donors or haploidentical donor in RR HL patients.Inclusion criteria were allo-HSCT performed during the same period (2010-2014); chemosensitive disease at allo-HSCT (complete + partial remission); T-cell replete haplo-HSCT using post-transplantation Cy. Haplo-HSCT were performed in 3 Centers (Humanitas Research Hospital, Rozzano; Ospedale San Martino, Genova; Institut Paoli Calmettes, Marseille, France) and HLA identical transplantation, both from related or unrelated donor, in centers from the Gruppo Italiano Trapianto di Midollo e cellule staminali periferiche (GITMO). 65 patients received Haplo-HSCT and 133 HLA-identical (HLA-id) transplantation. The institutional review board of each center approved the study. Patients and transplant characteristics were reported in Table 1. The median follow up was 30.6 months (range 0.2-74.1).Myeloid engraftment was slower in haplo group than HLAid group (20 days vs 14 day). In the haplo group, 2 out 3 patients had graft failure because of donor specific antibodies (DSA), and 1 patient dead from pneumonia before engraftment.In the Haplo and HLA-id group, the incidence of grade 2-4 acute GVHD was 15% vs 16% (p= 0.9) and chronic GVHD were and 18% vs 32% (p 0.06), respectively.For the whole cohort, the 2-year PFS, OS, relapse incidence (RI), and 1y-NRM were 45%, 66%, 38%, and 14%, respectively. The PFS, OS, and RI were significantly better in patients in CR compared to those in PR (55% vs 29% p= 0.001, 74% vs 55% p= 0.03, 27% vs 55% p<0.001, respectively), whereas the 1-year NRM was similar (15% vs 16% p= 0.9). After Haplo-HSCT and HLA-id HSCT, 2-year PFS was 63% vs 37% (figure 1A, p= 0.03), the 2-year OS was 67% vs 63% (p= 0.6), and the 1-year NRM was 13% vs 15%, (p= 0.9), respectively. The 2-year RI was significantly lower in the haplo group (figure 1B, 24% vs 44%, p= 0.008). We analyzed the clinical outcome in specific sub-groups of patients, coupling disease status and donor. Patients in CR receiving haplo-HSCT showed a significantly better 2-year PFS and lower 2-year RI compared to those allografted by HLA-id donor (figure 1C75% vs 47%, p<0.001 and 11% vs 34%, p<0.001, respectively). No statistically differences were founded in terms of OS and NRM. In PR patients, we found a similar outcome between patients receiving haploidentical donor or HLAid donor. The 2-year PFS was 44% vs 22%, p<0.001; and the 2-year RI was 44% vs 60%, p<0.001 (figure 1D).In multivariate analysis, donor type (haplo vs HLA-id HR 0.51, p<0.001) and disease status before transplantation (CR vs PR HR 0.37, p= 0.014) were independent predictors of PFS as well as they predict the risk of relapse (donor type HR 0.37, p<0.001; disease status, HR 0.43, p= 0.006). Disease status at transplantation and age (as continuous variable) were independently associated to OS (CR vs PR HR 0.57, p= 0.02; age HR 0.04, p= 0.006).This analysis suggested that haplo-HSCT using T-cell replete stem cells and PT-Cy is more effective than HLA-id donor because of a significant reduction of relapse risk in chemosensitive RR HL patients, challenging the question of donor choice. However, prospective comparative studies are needed to draw definitive conclusions. [Display omitted] DisclosuresCiceri:GSK: Other: B-thalassemia gene therapy was developed by Fondazione Telethon and Ospedale San Raffaele and has been inlicenced by GSK that provides funding for the clinical trial, Research Funding. Specchia:Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria. Carlo-Stella:ADC Therapeutics: Research Funding. Rambaldi:Novartis, Amgen, Celgene, Sanofi: Other: Travel, Accomodations, Expenses; Novartis, Roche/Genentech, Amgen, Italfarmaco: Consultancy. Santoro:Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees. Corradini:Celgene: Honoraria; Roche: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Sanofi: Honoraria; Amgen: Honoraria; Gilead: Honoraria.

An Antithymocyte Globulin-Free Conditioning Regimen Using Fludarabine and Cyclophosphamide Is Associated with Good Outcomes in Patients Undergoing Matched Related Family Donor Transplantation for Aplastic Anemia

Allogeneic hematopoietic stem cell transplantation (HSCT) using fludarabine (Flu)-based conditioning regimens are being increasingly being used in patients with aplastic anemia (AA). We describe an antithymocyte globulin (ATG)-free conditioning regimen consisting of Flu and cyclophosphamide (Cy) in patients undergoing matched related donor (MRD) HSCT for AA. Between 2004 and 2019, 212 patients underwent MRD HSCT using Flu (30 mg/m2/day for 6 days) and Cy (60 mg/kg/day for 2 days) for conditioning. The graft source was peripheral blood stem cells in all patients. Graft-versus-host disease (GVHD) prophylaxis consisted mainly of cyclosporine and methotrexate, although 41 patients received post-transplantation Cy as part of a study. Engraftment occurred in 91% of patients at a median of 16 days, whereas 4 patients (1.8%) experienced primary graft failure and 15 (7.1%) died before achieving engraftment. Toxicity was minimal. The incidence of grade II-IV acute GVHD (aGVHD) was 27.9%, and that of grade III-IV aGVHD was 11.3%. Chronic GVHD occurred in 41.6%. 80% were free of immunosuppression at 60 months and long-term complications were seen in 8.4%. At a median of 46 months, 158 patients were alive and well, with a 5-year overall survival (OS) of 75.3 ± 3.0%. The 5-year OS was 80.6 ± 4.1% for patients age <20 years (n=93), 74.5 ± 4.6% for those age 20 to 40 years (n=91), and 59.7 ± 9.5% for those age >40 years (n=28) (P=.11). Patients classified as low risk had better OS compared with those at high risk (93.2 ± 2.9% versus 65.7 ± 4.1%; P=.000). Factors affecting OS on multivariate analysis included aGVHD (P=.02) and graft failure (P=.000). This large series using Flu/Cy for conditioning before MRD HSCT confirms good outcomes in patients with AA, with excellent outcomes in low-risk patients. Suitable modifications are needed to improve outcomes in high-risk patients.

Risk Factors for Overall Survival in Children with High Risk Acute Myeloid Leukemia (HR AML) after Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) with Different Intensity of Conditioning Regimens

Background: Traditionally, children with AML undergo аllo-HSCT with myeloablative conditioning (MAC). It is known that MAC is associated with significant transplant-related morbidity and mortality. Reduced-intensity conditioning (RIC) is used in patients not eligible for conventional conditioning therapy due to poor performance status and severe toxic complications after previous chemotherapy. RIC is a well-established treatment strategy in adult patients with comorbidities. But there is no conclusive evidence to support efficacy of RIC allo-HSCT in children suffering from different malignant diseases including AML. The aim: To compare efficacy of different intensity conditioning regimens in children with high risk (HR) AML (according to AML-BFM protocols 1998 and 2004) and to identify factors which have a prognostic significance for overall survival (OS). Patients and methods: Retrospective analysis was performed in 192 patients (pts) with AML (median age of 10 years (0.5-18 y.o.), who received allo-HSCT at R.M. Gorbacheva Research Institute between 08/2000 and 09/2019. MAC (busulfan- or treosulfan-based) were used in 109 pts: 1st CR - 46 pts (MRD+ n=11), 2nd CR - 18 pts, 3rd CR - 1 pt, relapse - 44 pts. Allo-HSCT with RIC were performed in 83 pts: 1st CR - 32 pts (MRD+ n=13), 2nd CR -19 pts, 3rd CR - 4 pts, relapse -28 pts (p=0,674). RIC consisted of fludarabine (30 mg/m2/d x 5 days) + melphalan (70 mg/m2/d x 2 days) or fludarabine (30 mg/m2/d x 5 days) + busulfan (4 mg/kg/d x 2 days). Indication for RIC allo-HSCT was poor performance status (Lansky/Karnofsky score ≤70%), or organ dysfunction due to previous therapy, or infectious complications at the moment of allo-HSCT. Allo-HSCT from matched related donor was performed in 30 pts (16%), from matched unrelated donor - in 98 pts (51%), haploidentical - in 64 pts (33%) and the donor distribution was not different between groups (p=0,878). Post-transplant Cy was included in GVHD prophylaxis regimens in 102 pts (53%). OS were estimated using Kaplan-Meier curves. Univariate analyses were performed using the log rank test for OS, Grey test for cumulative incidences. Multivariate analyses were performed using the Cox proportional-hazard model. Results: Median follow-up was 5 years for МАС, 4.5 years for RIC. In both groups the median time to neutrophil engraftment &amp;gt;=0,5x109/l was D+16 (range D+8-52). Engraftment was observed in 67 pts (81%) after RIC and 94 pts (86%) after MAC (p=0,231). OS after RIC allo-HSCT in the 1st CR was 76% and after MAC - 68% (p=0,014), in 2nd CR 50% after RIC and 54% after MAC (p=0,058), in advanced disease 14% after RIC and 16% after MAC (p=0,394). The transplant-related mortality rate was 19% after RIC and 22% after MAC (p=0,546). Risk of relapse was 28% after RIC and 26% after MAC (p=0,456). Factors influencing OS after MAC were: 1) Remission status at the moment of allo-HSCT (р=0.001); 2) Presence of aGVHD grade I-II (р=0,005); 3) Relapse or MRD+ status after allo-HSCT (р=0.012); 4) Lansky score &amp;gt;70% (р=0,024). Factors influencing OS after RIC were: 1) Remission status at the moment of allo-HSCT (1st remission) (p=0,001); 2) Lansky score &amp;gt;70% (р=0,004). Conclusion: The effectiveness of RIC and MAC is comparable in children with HR AML, but RIC demonstrated better results in 1st CR. The presence of I-II grade aGVHD had positive effect in MAC. Factors influencing OS in both groups were disease status at the moment of allo-HSCT and performance status before allo-HSCT The use of RIC can be effective in patients, especially those who have undergone allo-HSCT in the 1st remission, while minimizing regimen-related toxicity in children who have undergone previous intensive treatment. Multicenter studies are warranted, especially for patients in the first CR, where long-term complications are of most importance. Disclosures No relevant conflicts of interest to declare.

Cyclophosphamide-Induced Tolerance in Allogeneic Transplantation: From Basic Studies to Clinical Application.

Immune tolerance against alloantigens plays an important role in the success of clinical organ and allogeneic hematopoietic stem cell transplantation. The mechanisms of immune tolerance to alloantigens have gradually been elucidated over time. Although there have been numerous reports to date on the induction of tolerance to alloantigens, the establishment of mixed chimerism is well-known to be crucial in the induction and maintenance of immune tolerance for either of the methods. Since the early 1980s, the murine system of cyclophosphamide (Cy)-induced tolerance has also been examined extensively. The present review focuses on studies conducted on Cy-induced immune tolerance. Clinical data of patients with allogeneic transplantation suggest that the posttransplant Cy method to induce immune tolerance has been successfully translated from basic studies into clinical practice.

Effect of Cyclophosphamide on Hemorrhagic Cystitis Following Haploidentical Related Compared to Matched Related/Unrelated Donor Hematopoietic Stem Cell Transplantation: A 7-Year Tertiary Center Analysis

Introduction Hemorrhagic cystitis (HC) is a serious and common complication of hematopoietic cell transplantation (HCT) affecting both allogeneic (alloHCT) and haploidentical HCT recipients.The aims of this study were to determine the incidence, risk factors, severity, morbidity pattern and toxicity of treatment, and outcome of HC in recipients of HSCT at a single tertiary transplant center. Methods We analyzed all patients undergoing haploidentical (haploHCT) or MRD/MUD alloHCT at our bone marrow transplant unit from September 2012 through June 2019. In alloHCT group, 70% (n=205) of the patients received myeloablative conditioning consisted of Cy and only six patients (2%) received identical GVHD prevention with a post-transplant Cy-based regimen. Conversely; in haploHCT group, use of Cy-containing preparative regimen was not often (22.9 % (n=8)) but 77.1% (n=27) of the patients received post-transplant Cy. Results A total of 328 HSCTs were performed during the study period, of which 169 (51.5%) alloHSCT from MUD, 124 (37.8%) alloHCT from MRD and 35 (10.7%) haploHCT. Baseline characteristics of the patients were similar among two groups with regarding to age, diagnosis, disease status and intensity of conditioning. Hemorrhagic cystitis was diagnosed in 78 of 328 patients (23.8%) with a median follow up 7.4 months. Disease status at transplant, recipient age, cytomegalovirus antigenemia and the intensity of conditioning regimen were not associated with the development of HC. The incidence of HC was significantly higher in patients who received grafts from haploidentical donors compared to those receiving grafts from MRD/MUDs (54.3% (n=19) vs 20.1% (n=59), p Conclusion Conditioning regimen is an important factor in the development of HC and its mechanism has been well described. In our study, we could not demonstrate the increased HC risk of conditioning regimens including cyclophosphamide. We also showed that cyclophosphamide in MAC had similar HC risk compared with RIC containing cyclophosphamide.In this retrospective analysis, BK virus was detected 45 patients out of 78 patients with HC and BK viruria was not associated with HC severity.

Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) with Different Intensity Conditioning Regimens in Children with Very High Risk Acute Lymphoblastic Leukemia (VHR ALL): A Single-Center Experience

Background: Allo-HSCT with myeloablative conditioning (MAC) has traditionally been performed in patients with ALL and has been associated with significant transplant-related morbidity and mortality. Reduced-intensity conditioning (RIC) is used in patients not eligible for conventional conditioning therapy due to poor performance status and severe toxic complications after previous chemotherapy. RIC is a well-established treatment strategy in adult patients with comorbidities or in elderly patients. In contrast to the adults, the RIC pediatric experience is still sparse. The aim: to compare efficacy of reduced intensity conditioning (RIC) and myeloablative conditioning (MAC) for allo-HSCT in children suffering from very high risk (VHR) ALL. Patients and methods: This was a retrospective analysis performed in 233 patients (pts) with ALL (age - from 4 month till 18 y.o. (mediana 11 y.o.)), who received allo-HSCT at R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation between 12/2000 and 12/2017. MAC (busulfan or treosulphan containing) was used in 159 pts: 1st CR - 26 pts, 2nd CR -57 pts, 3rd or 4th CR 23 - pts, relapse -53 pts. Allo-HSCT with RIC was performed in 74 pts: 1st CR - 14 pts, 2nd CR -29 pts, 3rd or 4th CR - 12 pts, relapse -20 pts. RIC consisted of fludarabine (30 mg/m2/d x 5 days) + melfalan (70 mg/m2/d x 2 days) or fludarabine (30 mg/m2/d x 5 days) + busulfan (4 mg/kg/d x 2 days). The disease status was not different between groups (p=0.674) Indication for RIC allo-HSCT was poor performance status (Lanskoy/Karnovsky&lt;70%), organ dysfunction due to previous therapy or infectioous complications at the moment of allo-HSCT. Allo-HSCT from matched related donor was performed in 41 pts, from matched unrelated donor - in 131 pts, haploidentical - in 61 pts. Post-transplant Cy was included in GVHD prophylaxis regimens in 102 pts (44%). Results: Median follow-up was 5 years for МАС, 4.5 years for RIC. In both groups the median time to neutrophil engraftment &gt;=0,5x109/l was D+18 (range D+8-48). Transplant engraftment was observed in 64 pts (86%) after RIC and 150 pts (93%) after MAC (p=0,224). OS pts after RIC allo-HSCT performed in 1 CR 70% and after MAC - 85% (p=0,043), in 2 CR 56% after RIC and 49% after MAC (p=0,436), in 3 or 4 CR 34% after RIC and 25% after MAC (p=0,394). OS in patients with active disease was 16% in RIC-group and 18% in MAC-group (p=0,432). The transplant-related mortality rate was 18% after RIC and 20% after MAC (p=0,40). Risk of relapse was 37% after RIC and 42% after MAC (p=0,39). Acute GVHD II-IVgr developed in 32% pts after RIC and 33% after MAC (p=0,883), early infections were diagnosed in 63% in RIC-group, and 59% in MAC-group (p=0,356). Early toxic complications were observed (CTC): mucositis III-IV gr in 13% pts after RIC and in 54% pts after MAC (p=0,001), nephrotoxicity in 7% pts and in 21% pts (p=0,042), hepatitis gr II-III in 24% pts and in 57% pts, respectively (p=0,034), neurological complications in 22% pts and 42% pts, resp. (p=0,046). Conclusion: RIC allo-HSCT of VHR ALL in 2,3 or 4 CR pts ≤ 18 y.o. is effective and comparable with MAC allo-HSCT. Early toxic complications after RIC were less frequent. Possibly, the use of RIC can maintain efficacy while minimizing regimen-related toxicity in children who have undergone previous intensive treatment. Disclosures Moiseev: Pfizer: Other: Travel grants; BMS: Other: Travel grants; MSD: Other: Travel grants; Novartis: Consultancy, Honoraria, Other: Travel grants, Speakers Bureau; Celgene: Consultancy, Other: Travel grants; Takeda: Other: Travel grants.

Effect of Cyclophosphamide on Hemorrhagic Cystitis Following Haploidentical Related Compared to Matched Related/Unrelated Donor Hematopoietic Stem Cell Transplantation: A 7-Year Tertiary Center Analysis

Introduction: Hemorrhagic cystitis (HC) is a serious and common complication of hematopoietic cell transplantation (HCT) affecting both allogeneic (alloHCT) and haploidentical HCT recipients. Early urinary bleeding after transplant is usually attributed to toxic effects of cyclophosphamide (Cy) or other agents used in the conditioning regimen or for graft-versus-host disease (GVHD) prevention. HC occurring beyond 3 to 4 weeks after HCT is usually attributed to BK polyoma virus or other viruses, e.g. cytomegalovirus or adenovirus. The aims of this study were to determine the incidence, risk factors, severity, morbidity pattern and toxicity of treatment, and outcome of HC in recipients of HSCT at a single tertiary transplant center. Methods: We analyzed all patients undergoing haploidentical (haploHCT) or MRD/MUD alloHCT at our bone marrow transplant unit from September 2012 through June 2019. In alloHCT group, 70% (n=205) of the patients received myeloablative conditioning consisted of Cy and only six patients (2%) received identical GVHD prevention with a post-transplant Cy-based regimen. Conversely; in haploHCT group, use of Cy-containing preparative regimen was not often (22.9 % (n=8)) but 77.1% (n=27) of the patients received post-transplant Cy. Grading of HC was based on the system used by Droller et al. and classified as grade I if the hematuria was microscopic and grade II if macroscopic. The presence of clots in the urine was regarded as grade III and obstructive uropathy with or without renal impairment as grade IV HC, respectively. All patients with a clinical diagnosis of HC had urine and blood analyzed for presence of BK virus by PCR. Results: A total of 328 HSCTs were performed during the study period, of which 169 (51.5%) alloHSCT from MUD, 124 (37.8%) alloHCT from MRD and 35 (10.7%) haploHCT. Baseline characteristics of the patients were similar among two groups with regarding to age, diagnosis, disease status and intensity of conditioning (Table 1). Hemorrhagic cystitis was diagnosed in 78 of 328 patients (23.8%) with a median follow up 7.4 months. Disease status at transplant, recipient age, cytomegalovirus antigenemia and the intensity of conditioning regimen were not associated with the development of HC. In addition, use of bone marrow versus peripheral blood had no influence on development of hemorrhagic cystitis (p=0.16). The incidence of HC was significantly higher in patients who received grafts from haploidentical donors compared to those receiving grafts from MRD/MUDs (54.3% (n=19) vs 20.1% (n=59), p&lt;0.001). Interestingly, the incidence of Grade III-IV HC was higher in the alloHCT compared to the haploHCT groups (37.2% vs 2.1%, p&lt;0.001). In multivariate analysis of risk factors associated with HC, receiving conditioning regimen including Cy and the use of a haploidentical donor was not significantly associated with HC. The incidence HC with BK viruria at the time of diagnosis of HC was higher in the cohort of patients receiving grafts from MRD/MUD donors (61% vs 47%, p=0.04). and BK viruria was not associated with HC severity. We identified no significant association between adenovirus, HHV-6 or CMV in HC patients comparing the onset and resolution of HC. Neither HC nor grades III-IV HC was associated with overall survival. Conclusion: Conditioning regimen is an important factor in the development of HC and its mechanism has been well described. In our study, we could not demonstrate the increased HC risk of conditioning regimens including cyclophosphamide. We also showed that cyclophosphamide in MAC had similar HC risk compared with RIC containing cyclophosphamide. BK virus was frequently found to be a risk factor for HC. In this retrospective analysis, BK virus was detected 45 patients out of 78 patients with HC and BK viruria was not associated with HC severity. Table 1 Disclosures Özcan: Amgen: Honoraria, Other: Travel support; Novartis: Research Funding; Celgene Corporation: Research Funding, Travel support; MSD: Research Funding; AbbVie: Other: Travel support, Research Funding; Jazz: Other: Travel support; Janssen: Other: Travel support, Research Funding; Takeda: Honoraria, Other: Travel support, Research Funding; Archigen: Research Funding; Roche: Other: Travel support, Research Funding; Bayer: Research Funding; Sanofi: Other: Travel support; Abdi Ibrahim: Other: Travel support; BMS: Other: Travel support. Beksac:Celgene: Speakers Bureau; Janssen: Research Funding, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

CMV reactivation in allogeneic hematopoietic stem cell transplant patients receiving post-transplant cyclophosphamide.

e18533 Background: Post transplant cyclophosphamide (PTCY) has been shown to be an effective treatment for prevention of graft versus host disease (GVHD). However, this increased immune suppression rates may increase the risk of CMV reactivation. There is limited published data addressing CMV reactivation in this patient population. Additionally there is no data on the efficacy of prophylactic letermovir in the patients who have received PTCY. In this study we analyzed the incidence of CMV reactivation in patients treated with PTCY and those not treated with PTCY, as well as the efficacy of letermovir in preventing CMV reactivation in the PTCY population. Methods: We conducted a retrospective review of MUD, MRD, and haploidentical stem cell transplant patients at our institution from 1/1/2014 until 12/10/2018. We analyzed the incidence of CMV reactivation (PCR &gt; 137 DNA IU/ml), peak of CMV PCR titer and time to reactivation within the first 100 days post-transplant. Results: There were 150 patients with at least 60 days of follow-up that were included in this study. These patients were split into three groups: No post-transplant cyclophosphamide (NPTCY) (N = 64), received post-transplant cyclophosphamide (PTCY) (N = 70), and received PTCY and letermovir prophylaxis. (L-PTCY) (N = 15). The incidence of CMV reactivation was increased in the PTCY patients when compared to the NPTCY (44% vs 29%). In the NPTCY patients the donor (D) serostatus increased the risk of CMV reactivation (Recipient (R)+ D+ 73% vs R+D-36%) conversely in the PTCY group the donor CMV status did not influence reactivation rates (R+D+ 52% vs R+D- 81%). The CMV reactivation rate in the L-PTCY patients was lower when compared to the PTCY patients (21% vs 44%), additionally the L-PTCY patients had much lower peak CMV titers compared to PTCY group (445 vs 2112 IU/ml). Conclusions: This study demonstrates that there is an increased incidence of CMV reactivation in patients who receive PTCY. Additionally, the donor CMV serostatus does not appear to influence the incidence of CMV reactivation in patients receiving post-transplant CY. Although the number of patients in the L-PTCY group is small, it does appear to be an effective prophylactic treatment in patients receiving PTCY.

Oral Vs Intravenous Tacrolimus Post Allogeneic Stem Cell Transplant: A Retrospective Analysis

Introduction Tacrolimus (tacro) is commonly used for the prevention of graft vs host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT). Due to concerns of inadequate absorption, tacro is commonly administered intravenously (IV) in the immediate post allogeneic transplant period. Advantages to oral (PO) tacro include decreased need for multi lumen IV catheters, improved patients (pts) convenience, and reduced cost. We retrospectively analyzed differences in safety, tolerability, time to achieve therapeutic levels during the 1st 4 weeks and rates of acute GVHD. Methods IV tacro at 0.02 mg/kg by continuous infusion or PO tacro at 0.03 mg/kg twice daily was started between T-3 and T+5. Levels were assessed 3 times weekly. Dose was titrated to achieve a steady level between 7 and 14 ng/ml. GVHD was graded according to CIBMTR criteria. Results 54 pts were treated between Sep 2016 and July 2018. 21 who received PO tacro and 27 who received IV tacro were studied. 6 pts on PO tacro are still within 100 days post-transplant and will be reported in follow up. The median age was 59 years (range, 21-74), 52% were females, diagnoses were AML (54%), MDS (19%), ALL (15%), CML (6%), NHL (4%) and MF (2%). HCT-CI was 0, 1-3 and >3 in 23%, 54% and 23% of pts, respectively. Donors were match-unrelated (58%), match-related (27%), haploidentical (6%) and double umbilical cord (6%). Conditioning regimens were myeloablative (60%) and reduced intensity (40%). 60% of pts received rabbit ATG (3 mg/Kg). GVHD prophylaxis also included mini-MTX on days +1, +3, +5 and +11 (79%), MMF (15%), and MMF + post-transplant Cy (6%). Pts characteristics were similar between the 2 groups. 7 pts (33%) who initially started on PO tacro switched to IV due to poor absorption (3), mucositis (1), toxicity (1), GVHD (1) and patient's concern (1). Target therapeutic level was reached in 67% vs 81% during week 1, 86% vs 96% during week 2, 95% vs 96% during week 3, and 100% vs 96% during week 4, of pts on PO vs IV tacro, respectively. Median tacro level during the 1st 4 weeks was 12.6 ng/ml vs 11.2 ng/ml, acute kidney injury occurred in 23.8% vs 33.3% (p=.47) and increased bilirubin occurred in 4.7% vs 22.2% (p=.09), in pts on PO vs IV tacro. Posterior reversible encephalopathy was observed in 1 patient on PO tacro. Grade I and Grade II-IV acute GVHD incidence was 47.6% vs 14.8% (p=.01) and 47.6% vs 44.4% (p=.82) of pts on PO vs IV tacro. Stage 1-2 skin aGVHD rate was higher in the PO vs. IV group (90% vs 33.3%; p=.0001). There was no difference in rates of stage 3 skin (4.7% vs 3.7%), stage 1 GI (33.3% vs 33.3%), or stage 2-4 GI (14% vs 7.4%) aGVHD. None of the pts had stage 4 skin or any stage liver aGVHD. Conclusion PO tacro is safe and effective in the prevention of aGVHD in pts receiving myeloablative or RIC allo-SCT. The use of PO tacro during the 1st 4 weeks post-transplant was found to be associated with higher rate of stage 1-2 skin aGVHD and warrants further study.

Post Transplant Cyclophosphamide Following Myeloablative TBI As a Conditioning Regimen for High-Risk Patients with AML Who Relapse after Transplant with Busulfan-Containing Regimen

Introduction Allogeneic HSCT (alloHSCT) offers a potential cure for patients with AML; however, 40% of AML patients receiving alloHSCT will experience relapsed disease. Second alloHSCT can offer the best long-term survival but is associated with significant toxicity. Preliminary data suggests that TBI only preparative regimen with post-transplant HD Cy is associated with lower TRM compared to TBI/Cy. Methods We report on four patients with AML who experienced relapsed disease following alloHSCT with busulfan-containing preparative regimen. All patients received re-induction chemotherapy and 3 achieved remission. Two patients had significant pre-existing morbidities prior to transplant, and one patient had refractory disease. Each patient received a second alloHSCT transplant using a TBI only preparative regimen (1200-1320 cGy) and GVHD prophylaxis included HD Cy 50mg/kg/daily on Days +3 and +4 as well as tacrolimus and MMF starting on Day +5. MMF was discontinued at Day +30 post-transplant. Three patients received bone marrow from 10/10 HLA-matched unrelated donors. One patient received PBSC from an HLA matched parent donor. Results All four patients tolerated transplant with no transplant related mortality and no grade 3 toxicity. All patients achieved neutrophil and platelet engraftment at an average of 19.5 (range 14-25) and 19 (range 15-23) days post transplant, respectively. Fifty percent of the patients developed acute Grade I-II skin GVHD. One patient developed mild, limited chronic GVHD. All patients are currently alive and are at least one year post second-transplant. Three of the four (75%) patients are off immune suppression and remain in remission at 14, 15 and 20 months post HSCT. Conclusion TBI only preparative regimen with post transplant HD Cy may offer an alternative treatment option for AML patients who experience relapse following a prior busulfan-containing alloHSCT.