Superior Outcome Using Cyclosporin A Alone Versus Cyclosporin A Plus Methotrexate for Post-Transplant Immunosuppression In Children with Acute Leukemia Undergoing Hematopoietic Stem Cell Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4502-4502
Author(s):  
Bernd Gruhn ◽  
Melissa Weiß ◽  
Ilona Wolff ◽  
Felix Zintl ◽  
James F. Beck
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Cyclosporin A ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Graft Versus Leukemia ◽  
Significant Difference ◽  
Graft Versus Leukemia Effect

Abstract Abstract 4502 Graft-versus-host disease (GVHD) is a major complication and one of the main causes of death after hematopoietic stem cell transplantation (HSCT). The GVHD prophylaxis influences the incidence of GVHD, relapse rate, and patient's survival. GVHD is associated with graft-versus-leukemia effect, which is mediated by donor T lymphocytes and decreases the risk of relapse. Therefore, a reduced post-transplant immunosuppression might have a positive impact on patient's survival. The outcome of different immunosuppressive prophylaxis regimen for adult patients has been studied extensively, whereas the effect on children has yet to be determined. Therefore, we performed a retrospective study analyzing 62 children (median age, 11 years) with acute lymphoblastic leukemia (n=35) or acute myeloid leukemia (n=27) who underwent bone marrow (n=56), peripheral blood stem cell (n=4), or umbilical cord blood (n=2) transplantation in a single center between November 1984 and July 2008. All respective donors were HLA-identical siblings. The patients received an immunosuppressive prophylaxis consisting of cyclosporin A (CSA) plus methotrexate (MTX) (n=43) or cyclosporin A alone (n=19). Patients in the CSA+MTX arm received CSA at a total dose of 10 mg/kg/day on day -1, 5mg/kg/day on days 0 to 4, and 3 mg/kg/day starting on day 5, and in addition MTX at a dosage of 10 mg/m2 on days 1, 3, 6, and 11. The 19 patients in the CSA arm received CSA at a total dose of 3 mg/kg/day starting on day -1. Concerning the patient's gender, age, diagnosis, and state of remission prior to transplantation, the two groups did not differ significantly. Patients who received CSA alone as post-transplant immunosuppression had a significantly reduced cumulative incidence of relapse (5% versus 40%; p=0,002), a significantly increased 5-year event-free survival (84% versus 35%; p=0.001), and a significantly increased 5-year overall survival (84% versus 42%; p=0.004). Interestingly, the incidence of acute GVHD grade II-IV in patients in the CSA arm was equivalent to the CSA+MTX arm (26% versus 19%; p=0.440). In addition, we did not observe a significant difference in the cumulative incidence of chronic GVHD (32% in the CSA arm versus 23% in the CSA+MTX arm; p=0.428). There was also no significant difference in the cumulative incidence of treatment related mortality after 1 year (10% in the CSA arm versus 23% in the CSA+MTX arm; p=0.165). In conclusion, CSA alone for post-transplant immunosuppression allows a stronger graft-versus-leukemia effect and thereby reduces the relapse rate and the number of patients dying of leukemia effectively without increase of acute and chronic GVHD. Post-transplant immunosuppression consisting of CSA alone leads to a superior outcome and should be preferred in children with a HLA-identical sibling as donor. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Comparison of alemtuzumab, anti-thymocyte globulin, and post-transplant cyclophosphamide for graft-versus-host disease and graft-versus-leukemia in murine models

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245232
Author(s):  
Kiyomi Mashima ◽  
Iekuni Oh ◽  
Ken Fujiwara ◽  
Junko Izawa ◽  
Norihito Takayama ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Post Transplant ◽  
Graft Versus Leukemia ◽  
Graft Versus Leukemia Effect

Graft-versus-host disease is a major complication after allogeneic hematopoietic stem cell transplantation for hematological malignancies. Immunosuppressive drugs, such as anti-thymocyte globulin, alemtuzumab, and post-transplant cyclophosphamide, have been used to prevent graft-versus-host disease in HLA-mismatched haploidentical hematopoietic stem cell transplantation. Here, we investigated whether these drugs could ameliorate graft-versus-host disease without diminishing the graft-versus-leukemia effect by using a xenogeneic transplanted graft-versus-host disease/graft-versus-leukemia model. Anti-thymocyte globulin treatment diminished graft-versus-host disease symptoms, completely depleted the infiltration of inflammatory cells in the liver and intestine, and led to prolonged survival. By contrast, improvement after post-transplant cyclophosphamide treatment remained minimal. Alemtuzumab treatment modestly prolonged survival despite an apparent decrease of Tregs. In the graft-versus-leukemia model, 1.5 to 2.0 mg/kg of anti-thymocyte globulin and 0.6 to 0.9 mg/kg of alemtuzumab reduced graft-versus-host disease with minimal loss of graft-versus-leukemia effect. Mice treated with 400 mg/kg of post-transplant cyclophosphamide did not develop graft-versus-host disease or leukemia, but it was difficult to evaluate the graft-versus-leukemia effect due to the sensitivity of A20 cells to cyclophosphamide. Although the current settings provide narrow optimal therapeutic windows, further studies are warranted to maximize the benefits of each immunosuppressant.

scholarly journals A Phase II Study of Decitabine Followed By Allogeneic Hematopoietic Stem Cell Transplantation in High-Risk Patients with Myeloid Malignancies

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2107-2107
Author(s):  
Christopher R. D'Angelo ◽  
Aric C. Hall ◽  
Kyungmann Kim ◽  
Ryan J. Mattison ◽  
Walter L. Longo ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Infectious Complications ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Risk Patients

Abstract Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for myelodysplastic syndrome (MDS) and high-risk acute myeloid leukemia (AML). Patients with high-risk disease have a markedly increased risk of relapse and death following transplant (Armand et al, Blood, 2014). Those who remain disease-free are at risk of severe morbidity from graft-versus- host-disease (GvHD). These issues highlight the importance of improved allo-HSCT platforms designed to reduce relapse rate without increasing risk of GvHD. Decitabine has minimal non-hematologic toxicity and proven efficacy in myeloid diseases (Blum et al, PNAS, 2010). Use of post-transplant cyclophosphamide has demonstrated improved rates of GvHD following allo-HSCT using haplo-identical donors (Bashey et al, JCO, 2013). No studies have reported on outcomes in patients undergoing decitabine immediately prior to transplantation followed by post-transplant cyclophosphamide (PTCy). We hypothesized that the combination of decitabine induction prior to transplant and PTCy would be safe and result in improved disease control with low rates of GVHD, translating into improved survival in a high-risk transplant cohort. Methods In this single-arm, single institution trial, eligible patients received 10 days of IV decitabine at 20mg/m2 no sooner than 24 days and no later than 17 days prior to conditioning. Myeloablative conditioning included fludarabine (50mg/m2 day-5-2), busulfan (IV 3.2mg/kg/day -5-2), and 4 Gy total body irradiation on day -1. Patients above age 65 received a 25% busulfan dose reduction. Patients received a fully or partially matched related bone marrow graft on day 0. GvHD prophylaxis included 50mg/kg of IV cyclophosphamide on day +3-4. Patients with fully matched donors received only PTCy while those with partially matched donors also received mycophenolate mofetil through day +35 and tacrolimus through day +180. Results We enrolled 20 patients, fifteen patients with AML and 5 with MDS. The cohort had a median age of 64 (29-73) and was predominantly male (14/20, 70%). Eight (40%) patients scored as high risk by the HSCT comorbidity index. Eighteen patients (90%) had a high or very high-risk score by the refined disease risk index. All patients received decitabine and 18/20 (90%) underwent transplantation; 2 patients did not receive a transplant due to infectious complications. The majority of patients received a haplo-identical graft (13/18, 72%), and the remaining 5 received a matched related graft. Outcomes are reported in table 2 and figure 1. There were no engraftment failures. Five patients, 3 MDS and 2 AML, are long-term survivors with median follow-up over 3 years. One patient developed donor derived MDS and required a second transplant. Most transplanted patients (13/18, 72%) survived to day 100 with a median post-transplant survival of 138 days. There were 15 deaths on study with the majority due to underlying disease. Six patients (6/20, 30%) died of infectious complications or did not receive a transplant due to infection. Incidence of grade 3-4 acute GvHD was low among those surviving at least 40 days from transplant (3/17, 17%). There were also low rates of chronic GvHD among the 12 patients alive without ongoing GvHD at day 100 (2/12, 17%). Conclusions Decitabine induction followed by myeloablative conditioning in this high-risk population resulted in a high treatment related mortality of 40%. Still, outcomes fell into an expected range for high-risk myeloid disease in an elderly and comorbid population. Based on expected outcomes for high-risk patients from the literature (Armand et al, Blood, 2014), decitabine did not markedly improve overall survival outcomes, recognizing that no direct comparisons are available in our limited study population. Decitabine may increase the risk of peri-transplant infections by contributing to a cumulative immunologic insult combined with disease-related immunosuppression and transplant-related toxicity, highlighting the importance of strict vigilance for infections within this setting. Diligent monitoring may improve infectious outcomes as shown in the second half of the cohort; only two out of the latter 10 patients on protocol died of treatment related complications. There were no cases of engraftment failure. Rates of acute and chronic GvHD using a PTCy platform were low and support other studies reporting this benefit. Disclosures No relevant conflicts of interest to declare.

Allogeneic hematopoietic stem cell transplantation in thalassemia major: results of a reduced-toxicity conditioning regimen based on the use of treosulfan

Blood ◽  
2012 ◽  
Vol 120 (2) ◽  
pp. 473-476 ◽  
Author(s):  
Maria Ester Bernardo ◽  
Eugenia Piras ◽  
Adriana Vacca ◽  
Giovanna Giorgiani ◽  
Marco Zecca ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Hematopoietic Stem

Abstract Sixty thalassemia patients (median age, 7 years; range, 1-37) underwent allogeneic hematopoietic stem cell transplantation (HSCT) after a preparation combining thiotepa, treosulfan, and fludarabine. Before HSCT, 27 children were assigned to risk class 1 of the Pesaro classification, 17 to class 2, and 4 to class 3; 12 patients were adults. Twenty patients were transplanted from an HLA-identical sibling and 40 from an unrelated donor. The cumulative incidence of graft failure and transplantation-related mortality was 9% and 7%, respectively. Eight patients experienced grade II-IV acute GVHD, the cumulative incidence being 14%. Among 56 patients at risk, 1 developed limited chronic GVHD. With a median follow-up of 36 months (range, 4-72), the 5-year probability of survival and thalassemia-free survival are 93% and 84%, respectively. Neither the class of risk nor the donor used influenced outcome. This treosulfan-based preparation proved to be safe and effective for thalassemia patients given allogeneic HSCT.

A Prospective Cost Analysis of Non-Myeloablative Hematopoietic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2239-2239
Author(s):  
Chris Skedgel ◽  
Jo-Ann Edwards ◽  
Jean Roy ◽  
Andrea McNeil ◽  
Yvonne Gulliver ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Hospital Admissions ◽  
Chronic Gvhd ◽  
Direct Costs ◽  
First Year ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
The Cost

Abstract Hematopoietic stem cell transplantation (HSCT) is an intensive medical therapy used to treat both malignant and non-malignant conditions. Non-myeloablative transplantation (NMT) is an emerging transplant modality often performed on an outpatient basis. While NMT is associated with fewer acute complications compared to myeloablative HSCT, long-term complications, particularly chronic graft vs host disease (GvHD), are of concern. To our knowledge, there have been few economic evaluations of NMT and none in a Canadian healthcare environment. We prospectively developed and validated a process for capturing the costs and outcomes of NMT in order to estimate the cost per patient of NMT at a Canadian transplant centre. Ten consecutive patients undergoing NMT were followed from the first day of conditioning (Day −11) until either 1 year post-transplant or death. Donor costs were also recorded. All patient encounters, procedures and interventions during the study period were prospectively recorded. Nursing and other non-physician human resource costs were calculated based on recorded contact times and salaries. Physician costs were derived from Nova Scotia fee codes. Costs of hospital admissions were derived from Ontario Case Costing Initiative (OCCI) data and were specific to the primary diagnosis. Drug costs were based on acquisition costs at hospital and community pharmacies. Materials and equipment costs were based on costs at the QEII Health Sciences Centre, Halifax NS. The proportion of administrative costs to direct costs was derived from OCCI data and applied to local direct costs. All costs are in 2005 Canadian dollars ($CAN). Ten patients were followed for a median of 12 months (range 3.6–12) from September 2003 to April 2005. Eight patients were male and the median age of the cohort was 60 years (19–73). Five patients had AML; 3 had lymphoma and 2 had multiple myeloma.Cyclophosphamide and fludarabine were used as conditioning and tacrolimus and mycophenolate mofetil were used as GvHD prophylaxis. There were 7 hospital admissions among the 10 patients: 3 before day 100 and 4 after day 100. Eight patients survived at least one year post-transplant. No patients developed acute GvHD, while all 8 patients surviving to 1 year post-transplant developed chronic GvHD. Three patients relapsed within 1 year. The average cost per NMT was $CAN 43,377 of which $CAN 31,761 were recipient costs, $CAN 2,562 were donor costs and $CAN 8,675 were equipment and overhead costs. The key cost driver was hospital admissions for complications and/or palliative care at $CAN 9,793 per recipient. Physician fees ($CAN 6,958) and chemotherapy ($CAN 6,485) were also significant. Compared to published estimates of the cost of myeloablative HSCT, NMT appears considerably less costly in the first year post-transplant. Our analysis suggests that the lower cost of NMT was largely attributable to the limited amount of inpatient care these patients received. Further follow-up will be informative since the major complications of NMT including chronic GvHD and relapse may impact per transplant cost after the first year post-transplant. Direct comparison with myeloablative HSCT using our prospective costing method is also planned.

Risk Factors for Late Infections after Allogeneic Hematopoietic Stem Cell Transplantation from a Matched Related Donor.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2848-2848
Author(s):  
Marie Robin ◽  
Raphaël Porcher ◽  
Renato De Castro Araujo ◽  
Régis Peffault de Latour ◽  
Agnès Devergie ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Viral Infection ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
First Year ◽  
Hematopoietic Stem ◽  
Cmv Status

Abstract After allogeneic hematopoietic stem cell transplantation (HSCT), late infections represent a major cause of morbidity and mortality but little has been previously reported. In a retrospective cohort study, late infections incidence was determined in 196 long-term survivors after matched related HSCT. Only patients transplanted for aplastic anemia, chronic myeloid leukemia (CML) and acute myeloblastic leukemia (AML) were included in this study. Median follow-up was 8 years. Among 30 patients who died beyond the first year, 9 patients died from graft-versus-host disease (GVHD) and 10 from infections. Bacterial late severe infections occurred in 30 patients, yielding an 8-year cumulative incidence of 15%. Late invasive fungal infection occurred in 8 patients corresponding to a cumulative incidence of 3.6%. Most viral infections were hepatitis C and VZV and overall late viral infection incidence was 35%. We identified 3 risk factors for bacterial infections in multiple analysis: CMV status (positive recipient and negative donor), irradiation based conditioning regimen and extensive chronic GVHD within the first year. Extensive chronic GVHD was the only risk factor of non-HCV viral infection in patients transplanted for AML or CML. Thus, late life threatening infections may occur in nearly a fourth of late survivors even after matched related transplantation and are associated not only with chronic GVHD but also with irradiation and to CMV status prior to transplantation.

Second Allogeneic Hematopoietic Stem-Cell Transplantation Using Fludarabine Treosulfan Conditioning Regimen in Patients Previously Treated with Busulfan-Based Regimens; Myeloablation with Acceptable Toxicity.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2255-2255 ◽  
Author(s):  
Avichai Shimoni ◽  
Avital Rand ◽  
Noga Shem-Tov ◽  
Izhar Hardan ◽  
Yulia Volchek ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
High Dose ◽  
Primary Malignancy ◽  
Hematopoietic Stem ◽  
Reduced Toxicity ◽  
Disease Free

Abstract Abstract 2255 Poster Board II-232 The prognosis of patients (pts) with leukemia who relapse after a prior autologous and or allogeneic hematopoietic stem cell transplantation (SCT) is dismal. A second allogeneic SCT can salvage some of these pts but myeloablative conditioning is associated with high rates of non-relapse mortality (NRM) in this setting and a relatively poor outcome. Reduced intensity conditioning allows reduction of NRM following a second SCT, but may be associated with a high relapse rate, mostly when leukemia is not in remission at the time of SCT. Similarly, allogeneic SCT for pts who develop secondary leukemia after a prior autologous SCT for a primary malignancy is associated with similar risks. The combination of fludarabine and treosulfan (FT) has been previously reported as a dose intensive myeloablative regimen with reduced toxicity and effective anti-leukemia capability, but its merit in second SCT is not defined. We explored a regimen consisting of fludarabine (total 150 mg/m2) and treosulfan (total 30-36 gr/m2) with the addition of ATG to recipients of unrelated or mismatched donor SCT, as a conditioning regimen for a second SCT. The study included 17 pts, 10 male, 7 female, median age 58 years (range, 20-70). Patient diagnosis at second SCT was AML (n=11), MDS (n=3), myelofibrosis (n=2) and CML in accelerated phase (n=1). The first transplant was autologous (n=6) or allogeneic (n=11). Autologous SCT was given for AML (n=3, 1 of them APL) or for a primary malignancy (lymphoma - 2, multiple myeloma -1). Second allogeneic SCT was given for relapse after a prior SCT or for secondary AML/MDS in the 3 pts having autologous SCT for lymphoma and myeloma. The Donor for the second SCT was an HLA-match sibling (n=6) or matched unrelated (n=11). In the 11 pts having a second allogeneic SCT after failure of a first allogeneic SCT the donor was the same donor in 3 transplants and a different donor in 8 transplants. The conditioning regimen for the first SCT contained high-dose intravenous busulfan (12.8 mg/kg) in 9 pts and reduced dose busulfan (6.4-9.6 mg/kg) in 5 pts. The three pts with primary lymphoma and myeloma were given BEAM and high-dose melphalan, respectively. The median time between the first and second SCT was 28 months (range, 3-48 months). Only 4 pts were in remission at the time of second SCT. Six pts were chemo-refractory and 7 pts were transplanted in untreated malignancy. Results: 12 pts engrafted with a median time to ANC > 0.5 × 109/L of 12 days (range, 9-38) and for PLT > 20 × 109 of 15 days (range, 11-44). Five pts died prior to engraftment, 3 of infections, 1 of cerebral hemorrhage and 1 of graft failure. There were no deaths related to organ toxicity (e.g. VOD or pneumonitis) and no late deaths due to NRM. Acute GVHD grade II-IV occurred in 2 pts, cumulative incidence 28%. Chronic GVHD occurred in 4 of 8 evaluable pts, cumulative incidence 57%. There were no deaths attributed to acute or chronic GVHD. The cumulative incidence of NRM was 30% (95%CI, 14-62). Three pts relapsed with a cumulative incidence of 25% (95%CI, 9-69). In all, with a median follow-up of 12 months (range, 1-59 months) the estimated 2-year overall and disease-free survival were both 45% (95CI, 17-73). Best results were achieved in the group of 8 pts having a second SCT form a second allogeneic donor; 5 pts are currently disease-free for a median of 18 months (range, 3-38), despite transplantation in advanced phase; 3 refractory to salvage chemotherapy and one in untreated relapse after the first SCT. The estimated 2 year survival in this group was 60%, a promising outcome in this setting. In conclusion, the fludarabine-treosulfan regimen is feasible for a second allogeneic SCT. NRM especially in the early post-transplant period is substantial, but can be expected in a group of heavily pretreated pts, many with active and refractory leukemia. The regimen has a promising anti-leukemia effect in this setting with a low recurrence rate, especially when using a different donor than in the prior transplant. The FT regimen can be considered a reduced toxicity myeloablative regimen that is feasible in pts given a prior transplant including pts previously given myeloablative doses of busulfan. Disclosures: No relevant conflicts of interest to declare.

Role of Donor Clonal Hematopoiesis in Allogeneic Hematopoietic Stem-Cell Transplantation

2019 ◽  
Vol 37 (5) ◽  
pp. 375-385 ◽  
Author(s):  
Mareike Frick ◽  
Willy Chan ◽  
Christopher Maximilian Arends ◽  
Raphael Hablesreiter ◽  
Adriane Halik ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Clonal Hematopoiesis ◽  
Increased Risk

Purpose Clonal hematopoiesis of indeterminate potential (CHIP) occurs in the blood of approximately 20% of older persons. CHIP is linked to an increased risk of hematologic malignancies and of all-cause mortality; thus, the eligibility of stem-cell donors with CHIP is questionable. We comprehensively investigated how donor CHIP affects outcome of allogeneic hematopoietic stem-cell transplantation (HSCT). Methods We collected blood samples from 500 healthy, related HSCT donors (age ≥ 55 years) at the time of stem-cell donation for targeted sequencing with a 66-gene panel. The effect of donor CHIP was assessed on recipient outcomes, including graft-versus-host disease (GVHD), cumulative incidence of relapse/progression (CIR/P), and overall survival (OS). Results A total of 92 clonal mutations with a median variant allele frequency of 5.9% were identified in 80 (16.0%) of 500 donors. CHIP prevalence was higher in donors related to patients with myeloid compared with lymphoid malignancies (19.2% v 6.3%; P ≤ .001). In recipients allografted with donor CHIP, we found a high cumulative incidence of chronic GVHD (cGVHD; hazard ratio [HR], 1.73; 95% CI, 1.21 to 2.49; P = .003) and lower CIR/P (univariate: HR, 0.62; 95% CI, 0.40 to 0.97; P = .027; multivariate: HR, 0.63; 95% CI, 0.41 to 0.98; P = .042) but no effect on nonrelapse mortality. Serial quantification of 25 mutations showed engraftment of 24 of 25 clones and disproportionate expansion in half of them. Donor-cell leukemia was observed in two recipients. OS was not affected by donor CHIP status (HR, 0.88; 95% CI, 0.65 to 1.321; P = .434). Conclusion Allogeneic HSCT from donors with CHIP seems safe and results in similar survival in the setting of older, related donors. Future studies in younger and unrelated donors are warranted to extend these results. Confirmatory studies and mechanistic experiments are warranted to challenge the hypothesis that donor CHIP might foster cGVHD development and reduce relapse/progression risk.

scholarly journals Long-Term Follow-up of a Randomized Trial of Two Dose Levels of Antithymocyte Globulin in Haploidentical Hematopoietic Stem Cell Transplantation

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 20-20
Author(s):  
Yu Wang ◽  
Ren Lin ◽  
Lan-Ping Xu ◽  
Kai-Yan Liu ◽  
Xiao-Hui Zhang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Randomized Trial ◽  
Late Effects ◽  
Cumulative Incidence ◽  
Antithymocyte Globulin ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Free Survival

Background The optimal dose of antithymocyte globulin (ATG) with respect to the prevention of graft-versus-host disease (GVHD) following haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is under investigation. In our previous single-center randomized study, as compared with 6 mg/kg ATG, 10 mg/kg ATG was found to be associated with better GVHD prevention and superior GRFS, but an increase in infection-related deaths. Later on, in our multi-center randomized trial, 7.5 mg/kg ATG for GVHD prophylaxis was associated with reduced EBV and CMV infections without increased incidence of GVHD in comparison with 10.0 mg/kg ATG in haplo-HSCT. Methods We reanalyzed and updated the prospective, randomized trial (clinicaltrials.gov, NCT01883180) identifying the influence of 7.5mg/kg versus 10.0 mg/kg of ATG on clinical outcomes in haplo-HSCT with extended follow-up (N=145. Seventy-six patients received 7.5 mg/kg ATG (ATG-7.5), whereas the remaining patients received 10 mg/kg ATG (ATG-10). Results The median follow-up period was 1702 days (range, 23-2036 days). The rate of infection-related deaths in ATG-10 arm was double that of the ATG-7.5 arm (20.0% vs 11.8%; P=0.024). The 5 year cumulative incidence of relapse was not significantly different between the ATG-7.5 and ATG-10 groups (16.8% vs. 5.7%, P = 0.053). The 5 year cumulative incidence of non-relapse mortality was comparable between the ATG-7.5 and ATG-10 groups (27.6% vs. 28.7%, P = 0.938). The 5 year cumulative incidence of chronic GVHD (46.7% vs. 48.3%, P = 0.913), moderate-to-severe chronic GVHD (32.8% vs. 25.3%, P = 0.248), and severe chronic GVHD (17.1% vs. 13.3%, P = 0.505) were comparable between the ATG-7.5 and ATG-10 groups. The 5 year probabilities of disease-free survival (DFS) in the ATG-7.5 and ATG-10 groups were 55.6% and 65.7%, respectively (P = 0.281). The 5 year probability of GVHD-free/relapse-free survival (GRFS) in the ATG-10 group was significantly higher than that in the ATG-7.5 group (48.1% vs. 29.5%, P = 0.020). The 5 year cumulative incidence of late effects of grades 1-5 (67.2% vs. 71.2%, P = 0.695) and multiple late effects (26.2% vs. 25.4%, P = 0.920) were comparable between the ATG-7.5 and ATG-10 groups. In multivariate analysis, ATG-7.5 was associated with a significantly lower GRFS compared to ATG-10 (hazard ratio, 1.819; 95% confidence interval, 1.106-2.994; p=0.019). Conclusion it appears that 10 mg/kg ATG was found to be associated with superior GRFS and comparable GVHD and late effects, but an increase in infection-related deaths as compared with 7.5 mg/kg ATG for haplo-HSCT. Figure Disclosures No relevant conflicts of interest to declare.

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