scholarly journals Urgent Time to Allogeneic Hematopoietic Cell Transplantation: A National Survey of Transplant Physicians and Unrelated Donor Search Coordinators Facilitated by the Histocompatibility Advisory Group to the National Marrow Donor Program

2019 ◽  
Vol 25 (12) ◽  
pp. 2501-2506 ◽  
Author(s):  
Joseph Pidala ◽  
Tatenda G. Mupfudze ◽  
Tammy Payton ◽  
Juliet Barker ◽  
Miguel-Angel Perales ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
National Survey ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Advisory Group ◽  
Unrelated Donor

Impact of Defibrotide in the Prevention of Acute Graft-Versus-Host Disease Following Allogeneic Hematopoietic Cell Transplantation

2022 ◽  
pp. 106002802110681
Author(s):  
Rémi Tilmont ◽  
Ibrahim Yakoub-Agha ◽  
Nassima Ramdane ◽  
Micha Srour ◽  
Valérie Coiteux ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Control Group ◽  
Unrelated Donor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

Background Defibrotide is indicated for patients who develop severe sinusoidal obstructive syndrome following allogeneic hematopoietic cell transplantation (allo-HCT). Preclinical data suggested that defibrotide carries a prophylactic effect against acute graft-versus-host disease (aGVHD). Objective The purpose of this study was to investigate the effect of defibrotide on the incidence and severity of aGVHD. Methods This single-center retrospective study included all consecutive transplanted patients between January 2014 and December 2018. A propensity score based on 10 predefined confounders was used to estimate the effect of defibrotide on aGVHD via inverse probability of treatment weighting (IPTW). Results Of the 482 included patients, 64 received defibrotide (defibrotide group) and 418 did not (control group). Regarding main patient characteristics and transplantation modalities, the two groups were comparable, except for a predominance of men in the defibrotide group. The median age was 55 years (interquartile range [IQR]: 40-62). Patients received allo-HCT from HLA-matched related donor (28.6%), HLA-matched unrelated donor (50.8%), haplo-identical donor (13.4%), or mismatched unrelated donor (7.0%). Stem cell source was either bone marrow (49.6%) or peripheral blood (50.4%). After using IPTW, exposure to defibrotide was not significantly associated with occurrence of aGVHD (HR = 0.97; 95% CI 0.62-1.52; P = .9) or occurrence of severe aGVHD (HR = 1.89, 95% CI: 0.98-3.66; P = .058). Conclusion and Relevance Defibrotide does not seem to have a protective effect on aGVHD in patients undergoing allo-HCT. Based on what has been reported to date and on these results, defibrotide should not be considered for the prevention of aGVHD outside clinical trials.

scholarly journals Nonpermissive HLA-DPB1 mismatch increases mortality after myeloablative unrelated allogeneic hematopoietic cell transplantation

Blood ◽  
2014 ◽  
Vol 124 (16) ◽  
pp. 2596-2606 ◽  
Author(s):  
Joseph Pidala ◽  
Stephanie J. Lee ◽  
Kwang Woo Ahn ◽  
Stephen Spellman ◽  
Hai-Lin Wang ◽  
...  
Keyword(s):  
High Resolution ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Unrelated Donor ◽  
Key Points ◽  
Overall Mortality

Key Points High-resolution matching for HLA-A, -B, -C, and -DRB1 is required for optimal survival in myeloablative-unrelated donor transplantation. HLA-DPB1 nonpermissive mismatches should be avoided in otherwise matched transplants to minimize overall mortality.

Salvage Allogeneic Hematopoietic Cell Transplantation with Fludarabine and Total Body Irradiation (3 or 4 Gy) after Failure of First Allografts.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3272-3272
Author(s):  
Boglarka Gyurkocza ◽  
Thai M. Cao ◽  
Rainer F. Storb ◽  
Thoralf Lange ◽  
Wendy Leisenring ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Umbilical Cord ◽  
Total Body Irradiation ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Unrelated Donor ◽  
Idiopathic Myelofibrosis ◽  
Total Body

Abstract We analyzed data from 38 patients (median age = 56, range: 8 – 68 years) with acute leukemia (n=15), chronic idiopathic myelofibrosis (n=6), myelodysplastic syndrome with or without myeloproliferative disorder (n=5), chronic myeloid leukemia (n=4), non- Hodgkin lymphoma (n=4), aplastic anemia (n=2), multiple myeloma (n=1) and renal cell carcinoma (n=1), who underwent salvage allogeneic hematopoietic cell transplantation (HCT) for allograft failure. In 14 cases the original donors were used for second HCT, while in 24 cases different donors were identified (Table 1). Conditioning regimens for first HCTs included total body irradiation (TBI; 2 Gy) with or without fludarabine (Flu; n=28), myeloablative regimens (busulfan-cyclophosphamide, n=6; cyclophosphamide-TBI, n=2); and other, cyclophosphamide-anti-thymocyte globulin-based regimens (n=3). Conditioning for salvage HCT consisted of Flu 30 mg/m2/day on days -4 to -2 followed by TBI of 3 (n=24) or 4 (n=14) Gy on day 0. Cyclosporine and mycophenolate mofetil were used for postgrafting immunosuppression. The median time between first and salvage HCTs was 91 (range, 29 to 1004) days. Sustained second grafts were achieved in 34 patients (89%), while grafts failed in 4 patients (11%), all of whom had idiopathic myelofibrosis. With a median follow-up among surviving patients of 2.0 (range, 0.3 to 7.8) years, the 2 and 4 year Kaplan-Meier survival estimates were 49% (95% CI: 31%, 66%) and 42% (95% CI: 23%, 61%), respectively. The 2 year relapse-rate and non-relapse mortality were 36% (95% CI: 20%, 52%) and 25% (95% CI: 11%, 41%), respectively. The cumulative incidences of grades 2–4 acute and moderate-severe chronic graft-versus-host disease (GVHD) at 2 years were 42% and 41%, respectively. Four patients with chronic GVHD discontinued systemic immunosuppressive therapy at a median of 2.5 years. Within the limitations of the small patient numbers studied, TBI dose (3 vs. 4 Gy), same vs. different donors for salvage HCT, donor type (related, unrelated, HLA-haploidentical related vs. double umbilical cord), and HCT comorbidity scores did not appear to affect outcomes. Based on this retrospective multicenter analysis, we conclude that graft failure following allogeneic HCT can be effectively overcome by second transplantation using conditioning with Flu and low dose TBI (3 or 4 Gy), which should be further investigated in a prospective manner. Table 1. Donors in 1st and 2nd HCTs. HLA-MURD: HLA-matched unrelated donor; HLA-MMURD: HLA-mismatched unrelated donor, UCB: umbilical cord blood. 2nd HCT Different Donor 1st HCT Same Donor HLA-MURD HLA-MMURD Double UCB HLA-haploidentical HLA-identical sibling 11 11 - - - - HLA-MURD 17 3 10 4 - - HLA-MMURD 8 - 1 7 - - Double UCB 2 - - - 1 1

Allogeneic Hematopoietic Cell Transplantation (allo-HCT) Can Induce Durable Remission in Heavily Pretreated Relapsed Hodgkin Lymphoma. (HL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1192-1192
Author(s):  
Robert Chen ◽  
Joycelynne Palmer ◽  
Leslie Popplewell ◽  
Jessica Shen ◽  
Eileen Smith ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
High Dose ◽  
Unrelated Donor ◽  
Heavily Pretreated

Abstract Abstract 1192 Poster Board I-214 Background: Even though Hodgkin lymphoma (HL) is a curable disease, about, 20-30% patients are either refractory to induction chemotherapy or relapse post treatment. High dose chemotherapy and autologous HCT has been shown to be an effective salvage therapy for patients with relapsed HL. However, relapse continues to occur after auto-HCT, especially in patients with chemoresistant or poor-risk features at relapse. The prognosis of these patients is poor with limited options of treatment. Although allo-HCT offers both cytoreduction and potential graft-versus-tumor effect, its use in relapsed HL has been limited by non-relapse mortality (NRM) and patient co-morbidities induced by numerous prior treatments. To examine the potential impact of allo-HCT on survival and disease outcomes, we performed retrospective analysis of allo-HCT in relapsed/refractory HL to determine if allo-HCT can induce long-term remission in heavily pretreated relapsed HL. Results: Between January 2003 and December 2008, 29 patients with relapsed HL underwent allo-HCT at City of Hope National Medical Center. The median age was 37 (range: 14-63). 20 (69%) patients were chemosensitive at time of allo-HCT. 17 (59%) patients had prior auto-HCT. 16 (55%) patients received matched siblings and 13 (45%) received unrelated donor cells. 20 (69%) patients had prior radiation treatments. The median number of prior regimens was 5 (range: 2-8). 23 (79%) patients underwent a non-myeloablative conditioning regimen while 6 (21%) patients had a myeloablative regimen. 14 (48%) patients received Tacrolimus/Sirolimus as graft versus host disease prophylaxis and 15 (52%) patients received a combination of Cellcept/CsA, Cellcept/CsA/MTX, Tacrolimus/MTX, or Tacrolimus/Sirolimus/MTX. With a median follow up of 31.9 months (range: 9.7-69.1) for surviving patients, the results show: Conclusion: Allogeneic hematopoietic cell transplantation in heavily pretreated relapsed Hodgkin's lymphoma is feasible, tolerable, and can induce durable clinical remissions. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Total Body Irradiation without Chemotherapy as Conditioning for an Allogeneic Hematopoietic Cell Transplantation for Adult Acute Myeloid Leukemia

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Sultan Altouri ◽  
Mitchell Sabloff ◽  
David Allan ◽  
Harry Atkins ◽  
Lothar Huebsch ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Unrelated Donor ◽  
Relapsed Disease ◽  
Acute Myeloid

Current therapies for acute myeloid leukemia (AML), failing induction, are rarely effective. We report our experience in 4 patients with AML who received 16 Gy TBI prior to allogeneic hematopoietic cell transplantation (alloHCT), between June 2010 and May 2011. Patients were 20 to 55 years of age, 2 with relapsed disease and 2 with AML failing induction. An HLA-matched graft from related or unrelated donor was infused on day 0. All but one, who received a CD34+-selected graft, received methotrexate and tacrolimus +/− antithymocyte globulin, as GVHD prophylaxis. The other patient received tacrolimus alone. Neutrophil and platelet engraftment occurred at a median of 18 and 14 days, respectively. Patients were discharged at a median of 28 days. There were no unexpected toxicities in the first 30 days. One patient had cytomegalovirus (CMV) viremia and anorexia, at two months. One patient had grade 2 acute GVHD of the skin. One patient developed chronic GVHD of the eyes, mouth, skin, joints, and lung at 4 months. Two patients died from relapse of their leukemia at days 65 and 125. Two patients remain in remission beyond day 1500. 16 Gy TBI followed by an alloHCT for AML, failing induction, is feasible and tolerable.

scholarly journals Superior Outcomes with Fludarabine-Busulfan (Flu/Bu) Based Conditioning for Allogeneic Hematopoietic Cell Transplantation in Myelofibrosis - a Comparative Analysis By CIBMTR

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 912-912
Author(s):  
Guru Subramanian Guru Murthy ◽  
Soyoung Kim ◽  
Noel Estrada-Merly ◽  
Ronald M. Sobecks ◽  
Betul Oran ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
Multivariable Analysis ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Unrelated Donor ◽  
Free Survival ◽  
Grade 3

Abstract Background: Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative therapeutic modality for patients with myelofibrosis (MF). However, the optimal conditioning regimen for allo-HCT either in the myeloablative conditioning (MAC) or in the reduced intensity conditioning (RIC) setting is not well known. Methods: Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified adults aged ≥18 years with MF who underwent allo-HCT between the years 2008-2018. Donor types included matched sibling donor (MSD), 8/8 matched unrelated donor (MUD), and 7/8 MUD. Outcomes were compared separately in the MAC and RIC cohorts based on the most common conditioning regimens used in each setting - MAC [(Fludarabine/Busulfan (Flu/Bu) vs. Busulfan/cyclophosphamide (Bu/Cy)] or RIC [(Flu/Bu vs. Fludarabine/melphalan (Flu/Mel)]. Overall survival (OS), disease free survival (DFS), non-relapse mortality (NRM), relapse, acute and chronic graft versus host disease (GVHD) and GVHD-free relapse-free survival (GRFS) were evaluated. Survival analysis was done using Kaplan-Meier method and significant predictors were evaluated using Cox-proportional hazard regression method. Multivariable regression model included main effect (conditioning regimen) and covariates (patient age, gender, race, CMV match, disease subtype, DIPSS at HCT, comorbidities score (HCT-CI), Karnofsky performance status, prior therapy (ruxolitinib use/splenic radiation therapy/splenectomy), interval between diagnosis and transplant, conditioning intensity, stem cell source, donor-recipient HLA-match, GVHD prophylaxis, ATG/alemtuzumab use, transplant year, and center affect). All analyses were performed at a two-sided significance level of 0.05. Results: Of 872 patients who met the study criteria, 379 patients underwent allo-HCT using MAC (Flu/Bu=247, Bu/Cy=132) and 493 patients using RIC (Flu/Bu=166, Flu/Mel=327). Key baseline characteristics of the patients are summarized in Table 1. In multivariable analysis, significant differences in outcomes were observed in the MAC and RIC setting based on the choice of conditioning regimen (Table 2). In the MAC setting, Bu/Cy was associated with a higher risk of acute GVHD (grade 2-4 HR 2.33, 95% CI 1.67-3.25, p<0.01; grade 3-4 HR 2.31, 95% CI 1.52-3.52, p<0.01) and inferior GRFS (HR 1.94, 95% CI 1.49-2.53, p<0.01) as compared to Flu/Bu. In the RIC setting, Flu/Mel was associated with inferior OS (HR 1.80, 95% CI 1.15-2.81, p<0.01), higher risk of NRM (HR 1.81, 95% CI 1.12-2.91, p=0.01) and acute GVHD (grade 2-4- HR 1.45, 95% CI 1.03-2.03, p=0.03; grade 3-4 HR 2.21, 95%CI 1.28-3.83, p<0.01) as compared to Flu/Bu. These higher risks associated with Flu/Mel were primarily observed early post-transplant. The results were consistent when the outcomes were evaluated based on the two common melphalan doses employed in the RIC setting (100mg/m 2 vs 140mg/m 2). Conclusions: Our study demonstrates that the choice of conditioning regimen significantly influences the outcomes of allo-HCT in MF. The results favor Flu/Bu based conditioning in the MAC (lesser acute GVHD and better GRFS) and RIC (better OS, lower NRM, lower acute GVHD) setting. Hence, this aspect should be explored in future studies as the modification of conditioning strategies could lead to improved outcomes. Figure 1 Figure 1. Disclosures Guru Murthy: TG therapeutics: Other: Advisory board; Cardinal Health Inc.: Honoraria; Qessential: Consultancy; Guidepoint: Consultancy; Techspert: Consultancy; Cancerexpertnow: Honoraria. Sobecks: CareDX: Membership on an entity's Board of Directors or advisory committees. Scott: Bristol Myers Squibb: Consultancy, Honoraria, Research Funding. Saber: Govt. COI: Other.

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