scholarly journals Hematopoietic Cell Transplantation from an HLA-Mismatched Familial Donor Is Feasible Without Ex Vivo-T Cell Depletion after Reduced-Intensity Conditioning with Busulfan, Fludarabine, and Antithymocyte Globulin

2009 ◽  
Vol 15 (1) ◽  
pp. 61-72 ◽  
Author(s):  
Kyoo-Hyung Lee ◽  
Je-Hwan Lee ◽  
Jung-Hee Lee ◽  
Dae-Young Kim ◽  
Se-Hyung Kim ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Transplantation ◽  
Antithymocyte Globulin ◽  
Hematopoietic Cell Transplantation ◽  
Ex Vivo ◽  
Hematopoietic Cell ◽  
Cell Depletion ◽  
Reduced Intensity Conditioning ◽  
T Cell Depletion ◽  
Reduced Intensity

HLA-Haploidentical Familial Donor Hematopoietic Cell Transplantation without Ex Vivo- T Cell Depletion after Reduced-Intensity Conditioning of Busulfan, Fludarabine, and Anti-Thymocyte Globulin: A Preliminary Report.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3077-3077
Author(s):  
Kyoo-Hyung Lee ◽  
Seong-Jun Choi ◽  
Jung-Hee Lee ◽  
Ho-Jin Shin ◽  
Young-Shin Lee ◽  
...  
Keyword(s):  
T Cell ◽  
High Risk ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Cell Depletion ◽  
Reduced Intensity Conditioning ◽  
T Cell Depletion ◽  
Reduced Intensity

Abstract Animal hematopoietic cell transplantation (HCT) models and several small clinical trials showed that successful engraftment can be achieved across HLA-haplotype difference after reduced-intensity conditioning (RIC). Furthermore, decreased graft-versus-host disease (GVHD) and transplantation-related mortality (TRM) after RIC was shown in a swine leukocyte antigen-haploidentical HCT experiment. Therefore, a protocol investigating the role of RIC in HLA-haploidentical familial donor HCT was initiated in April 2004 and 20 patients [13 male and 7 female; median age 26.5 years (16–65)] without HLA-matched donor enrolled until June 2007. The diagnosis were AML (n=9), ALL (n=4), acute biphenotypic leukemia (n=1), MDS (n=4), and SAA (n=2), and all patients had high-risk features, i.e. first complete remission (CR) but with high-risk chromosomal abnormality (n=1), first CR after salvage (n=1), second CR (n=6), recurrent/refractory state (n=7), immunotherapy failure (n=4), and high-risk MDS (RAEB-1, n=1). The RIC included iv busulfan 3.2 mg/kg × 2, fludarabine 30 mg/m2 × 6, plus anti-thymocyte globulin [Thymoglobuline 3 mg/kg (n=17) or Lymphoglobuline 15 mg/kg (n=3)] × 4. After receiving G-CSF, the donors (13 mothers; 5 offsprings; and 2 HLA-haploidentical siblings) underwent 2 or 3 daily leukapheresis, and the collected cells were given to patients without T cell depletion [medians of; 7.9 (3.7–12.1)×108/kg MNC, 6.9 (3.6–73.5)×106/kg CD34+ cells, and 4.6 (1.8–8.5)×108/kg CD3+ cells]. GVHD prophylaxis was cyclosporine 3 mg/kg/day iv from day -1 and a short course of methotrexate. As a part of separate phase 1 study, the two most-recently enrolled patients received additional donor CD34+ cell-derived NK cells 6 weeks after HCT. Except one patients with SAA who died due to K. pneumoniae sepsis on day 18, all 19 evaluable patients engrafted with ANC> 500/μl median 17 days (12–53) and platelet> 20,000/μl median 23 days (12–100) after HCT. Eight patients experienced acute GVHD (grades I, II, III, and IV; 2, 3, 2, and 1, respectively). Cumulative incidences (CI) of overall and grade II-IV acute GVHD were 40 and 30%, respectively. Eight patients experienced chronic GVHD (limited, 4; extensive, 4; CI, 51%). Fourteen showed positive CMV antigenemia, while 2 suffered CMV colitis, which resolved after treatment. As early as 2 weeks after HCT, 15 of 16 evaluable patients, and, by 4 weeks, all of 17 evaluable patients showed donor chimerism ≥95% on STR-PCR, which was maintained until 24 weeks in all 11 patients tested. Thirteen patients are alive after median follow-up of 13.6 months (1.5–37.9; Kaplan-Meier survival, 55.6%). Of 16 patients with acute leukemia and high-risk MDS, 8 remain alive without recurrence (event-free-survival, 40.9%). Two patients died of K. pneumoniae sepsis and grade IV acute GVHD, respectively (CI of TRM, 11%). Immune recovery in 10 patients without relapse for > 6 months showed robust lymphocyte contents and immunoglobulin levels at 6 months (means of; 1,060/ul CD3+, 222/ul CD4+, 767/ul CD8+ cells, and 1,317 mg/dl IgG) and 12 months. After RIC, consistent engraftment and durable complete donor hematopoietic chimerism can be achieved from HLA-haploidentical familial donor. The frequencies of GVHD and TRM were low.

scholarly journals Association between preconditioning absolute lymphocyte count and transplant outcomes in patients undergoing matched unrelated donor allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning and anti-thymocyte globulin

2021 ◽  
Vol 12 ◽  
pp. 204062072110637
Author(s):  
Jeongmin Seo ◽  
Dong-Yeop Shin ◽  
Youngil Koh ◽  
Inho Kim ◽  
Sung-Soo Yoon ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cell Depletion ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Matched Unrelated Donor ◽  
T Cell Depletion ◽  
Reduced Intensity

Background: Allogeneic stem cell transplantation (alloSCT) offers cure chance for various hematologic malignancies, but graft- versus-host disease (GVHD) remains a major impediment. Anti-thymocyte globulin (ATG) is used for prophylactic T-cell depletion and GVHD prevention, but there are no clear guidelines for the optimal dosing of ATG. It is suspected that for patients with low absolute lymphocyte counts (ALCs), current weight-based dosing of ATG can be excessive, which can result in profound T-cell depletion and poor transplant outcome. Methods: The objective of the study is to evaluate the association of low preconditioning ALC with outcomes in patients undergoing matched unrelated donor (MUD) alloSCT with reduced-intensity conditioning (RIC) and ATG. We conducted a single-center retrospective longitudinal cohort study of acute leukemia and myelodysplastic syndrome patients over 18 years old undergoing alloSCT. In total, 64 patients were included and dichotomized into lower ALC and higher ALC groups with the cutoff of 500/μl on D-7. Results: Patients with preconditioning ALC <500/μl were associated with shorter overall survival (OS) and higher infectious mortality. The incidence of acute GVHD and moderate-severe chronic GVHD as well as relapse rates did not differ according to preconditioning ALC. In multivariate analyses, low preconditioning ALC was recognized as an independent adverse prognostic factor for OS. Conclusion: Patients with lower ALC are exposed to excessive dose of ATG, leading to profound T-cell depletion that results in higher infectious mortality and shorter OS. Our results call for the implementation of more creative dosing regimens for patients with low preconditioning ALC.

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