scholarly journals Feasible Outcomes of T Cell–Replete Haploidentical Stem Cell Transplantation with Reduced-Intensity Conditioning in Patients with Myelodysplastic Syndrome

2015 ◽  
Vol 21 (2) ◽  
pp. 342-349 ◽  
Author(s):  
Seung-Hwan Shin ◽  
Jung-Ho Kim ◽  
Young-Woo Jeon ◽  
Jae-Ho Yoon ◽  
Seung-Ah Yahng ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Myelodysplastic Syndrome ◽  
Cell Transplantation ◽  
Reduced Intensity Conditioning ◽  
Haploidentical Stem Cell Transplantation ◽  
Reduced Intensity

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.

Sustained Engraftment Using Fludarabine, Melphalan and Thiotepa Conditioning for Haploidentical Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5081-5081 ◽  
Author(s):  
Stefan O. Ciurea ◽  
Suhail Qureshi ◽  
Gabriela Rondon ◽  
Susana Pesoa ◽  
Pedro Cano ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conditioning Regimen ◽  
Hematologic Malignancies ◽  
Platelet Recovery ◽  
Haploidentical Stem Cell Transplantation ◽  
Cd34 Cells ◽  
Reduced Intensity

Abstract BACKGROUND: Haploidentical stem cell transplantation (HaploSCT) using mega-doses of CD34 cells and a T-cell depleted allograft has generally been performed in advanced hematologic malignancies using a fractionated TBI-based conditioning regimen (CR) with very high toxicity. Here we evaluated the results of a reduced intensity chemotherapy-only conditioning regimen (RIC) with fludarabine (F), melphalan (M) and thiotepa (T) for HaploSCT. METHODS: 24 patients (pts) with advanced hematologic malignancies (18 with AML/MDS, 3 with ALL, 2 with CML and 1 with T-cell lymphoma underwent HaploSCT from related donors at MDACC between 10/2001 and 04/2007. The median age was 36 years. At the time of transplantation 15/24 pts (63%) had relapsed or primary refractory disease and 37% were in remission. Pts received a median of 10.8x10e6 CD34 cells. The median number of CD3 cells infused was 1x10e4/kg. The number of allele mismatch was 3/10 in 4 pts, 4/10 in 10 pts, 5/10 in 9 pts and 6/10 in 1 pt. HLA antibody (AB) specificity was determined using fluorescent beads coated with single antigens and detected in a Luminex platform. The CR consisted of M 140 mg/m2 on day −8, T 10 mg/m2 on day −7, F 160 mg/m2 over 4 days on days −6, −5, −4, −3, and 1.5 mg/kg of rabbit ATG a day x 4 on days −6, −5, −4, and −3 (FMT). No GVHD prophylaxis and no growth factors were administered. The pts were evaluated for engraftment and 100-day transplant-related mortality (TRM). RESULTS: 23 pts were evaluable for engraftment. 1 pt died on day 27 due to respiratory failure. 19/23 pts (83%) engrafted with hematopoietic recovery with donor-derived cells. 18 pts achieved a full donor chimerism while 1 had progressive leukemia. Neutrophil recovery to ANC >0.5 x 10e9/l occurred after a median of 13 days and platelet recovery to >20 x 10e9/l occurred after a median of 13.5 days. 4 pts failed to achieve primary engraftment, presumably due to rejection. No statistically significant correlation was found between graft failure (GF) and KIR-ligand mismatch (KIR-LM). In fact KIR-LM were more common in the group of pts who engrafted (7/19) than in pts with GF (1/4). After 09/2005 when anti HLA AB were started to be done, 3/14 pts had GF, 2 of which had donor directed AB. The regimen was relatively well tolerated; 4 pts experienced grade 4 nonhematologic, organ toxicities. Cumulative day 100 TRM was 25%. 19/24 pts (79%) were in CR after transplant with 6 surviving at the last follow-up (OS 25%). Only 1 pt developed aGVHD (4.1%) and 5 pts developed cGVHD (20.8%) with 3 experiencing extensive GVHD. 9 pts (37.5%) relapsed after a median of 71.5 days post transplant. The distribution of KIR-LM in the GVH direction was similar in pts with and without relapse (3/9 pts with relapse and 5/15 pts without relapse). Causes of death were disease relapse in 9 pts, infections in 3 pts, pulmonary failure/MOF in 4 pts and cGVHD in 1 pt. CONCLUSIONS: The reduced intensity FMT regimen was sufficiently immunosuppressive to support rapid engraftment after HaploSCT in 83% of pts with advanced hematologic malignancies. In this small series, KIR-LM in the HVG or GVH direction were not associated with graft rejection or malignancy relapse. The role of anti-HLA AB need further evaluation. The rate of toxicity and 100-day TRM appears lower as compared with published studies of TBI-based CR. The FMT RIC merits further evaluation in studies of HaploSCT.

A Pilot Study of Reduced-Intensity Conditioning Stem Cell Transplantation with T-Cell Replete HLA-Mismatched Allograft from Child to Parent Patient for the Treatment of Refractory Adult T-Cell Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5406-5406
Author(s):  
Hiroshi Fujiwara ◽  
Atsuo Ozaki ◽  
Makoto Yoshimitsu ◽  
Heiichiro Hamada ◽  
Hideaki Kawada ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Pilot Study ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Induction Chemotherapy ◽  
Cell Leukemia ◽  
Reduced Intensity Conditioning ◽  
Adult T Cell Leukemia ◽  
Reduced Intensity

Abstract [Background/Purpose] Adult T-cell leukemia (ATL) is a most aggressive lymphoid malignancy with poor prognosis, and at present, allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been an only curative modality. Nevertheless, not only the aggressive nature of disease itself, but also the aging of patients older than 55 y.o. contribute to therapeutic impediments by comorbidity and difficulty of timely acquiring HLA-matched sibling donor. In this setting, allograft from child to parent patient is a realistic modality. We report a result of a prospective study evaluating the efficacy of reduced -intensity conditioning SCT (RIST) with HLA-mismatched allograft from child to parent for ATL patients. [Patients/methods] 5 patients (2 males, and 3 females) with ATL in progressive disease (PD) after induction chemotherapy with LSG15 regimen who had no HLA-identical sibling donors were enrolled. Patient median age was 59 y.o. All donors were sons with haploidentical HLA. Median age of donor was 29 y.o. KIR ligands were matched. Preparatory regimen consisted of fludarabine (180mg/m2), busulfan (8mg/m2) or cyclophosphamide (120mg/kg) and rabbit antithymocyte globulin (2.5mg or 5.0mg/kg). Stem cell source was G-CSF mobilized PBSC. Mean infused CD34 cell number was 8.3×106/kg (from 4.1 to 23.3 × 106/kg). GVHD prophylaxis consisted of tacrolimus or cyclosporine and short term methotraxate and mycophenolate mofetil. [Results] Median interval from induction chemotherapy to transplantation was 5 months. Median observation interval was 8 mo. (from 3.5 mo. to 31 mo.). All 5 cases had neutrophil engraftment at day 15 after transplantation. In 5 of 5 cases, complete donor T-cell chimerism were obtained by day 30. Overall survival (OS) and progression free survival (PFS) at 1 year was 50%, and 26.7%, respectively. Evaluation of peripheral residual disease demonstrated by HTLV-I proviral load and soluble interleukin-2 receptor (sIL-2R) value documented the strong disease suppression by this transplants. Analysis of NK cell kinetics revealed that donor-derived NK cells expanded and exerted killing activity mainly until 4 months after transplantation, and decreased in number thereafter. These findings indicated all achieved complete donor T-cell chimerism followed by clinical observations for graft vs. ATL effect. Although, disease progression occurred 4 of 5 cases, 2 achieved remission again with the longest response duration of 31 mo. All but UPN2 experienced GVHD (grade 2 to 4), and UPN2 had early relapse and died of ATL at 4 mo. after allo-HSCT. Frequent reactivations of cytomegalovirus were observed, but well controlled by ganciclovir. [Summary] In our pilot study, RIST with T-cell replete HLA-mismatched allograft from child to parent patient could provide timely donor acquisition and durable remission for all patients with refractory ATL. This setting may be one of realistic modalities for ATL patients who need alternative donors.

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