Haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion for the treatment of hematological malignancies

Huang, Xiao‐Jun; Dh, Liu; Ky, Lee; Xu, Lei; Chen, H; Wang, Han; Chen, Y-H.; Jz, Wang; Zy, Gao; Yc, Zhang; Jiang, Qian; Shi, Huidong; Lu, Dao-Pei

doi:10.1038/sj.bmt.1705445

Cited by 369 publications

(359 citation statements)

References 18 publications

(20 reference statements)

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“…GBM was collected on the 4th day of treatment by aspiration, and GPB was obtained on the 5th day by leukapheresis using a continuous‐flow blood cell separator (Gambro BCT, Lakewood, CO, USA; or Baxter, Chicago, IL, USA). The reason for using this protocol was that patients in our institute receive transplants composed of GBM plus GPB, which are harvested on days 4 and 5, respectively 31, 32…”

Section: Methodsmentioning

confidence: 99%

“…All patients received a myeloablative regimen, and conditioning was performed as previously described 31, 32, 34, 35. In HLA‐matched sibling transplants,32 patients received a regimen consisting of 80 mg/kg hydroxyurea orally on day 10, 2 g/m 2 /d cytarabine intravenously on day 9, 3.2 mg/kg/d busulfan intravenously on days 8 to 6 pre‐transplantation, 1.8 g/m 2 /d cyclophosphamide intravenously on days 5 to 4 pre‐transplantation and 250 mg/m 2 of methyl‐N‐(2‐chloroethyl)‐N'‐cyclohexyl‐N‐nitrosourea orally on day 3.…”

Section: Methodsmentioning

confidence: 99%

“…In HLA‐haploidentical donor transplants, patients received a regimen similar to HLA‐matched patients, except for the addition of 4 g/m 2 /d cytarabine on days 10 to 9 and 2.5 mg/kg/d antithymocyte globulin (SangStat) intravenously on days 5 to 2 pre‐transplantation. GVHD prophylaxis included cyclosporine A (CSA) and short‐term methotrexate (MTX) with mycophenolate mofetil (MMF) 31, 32…”

Section: Methodsmentioning

confidence: 99%

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Effect of the in vivo application of granulocyte colony‐stimulating factor on NK cells in bone marrow and peripheral blood

Han

et al. 2018

J Cellular Molecular Medi

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Granulocyte colony‐stimulating factor (G‐CSF) has been widely used in the field of allogeneic haematopoietic stem cell transplantation (allo‐HSCT) for priming donor stem cells from the bone marrow (BM) to peripheral blood (PB) to collect stem cells more conveniently. Donor‐derived natural killer (NK) cells have important antitumour functions and immune regulatory roles post‐allo‐HSCT. The aim of this study was to evaluate the effect of G‐CSF on donors' NK cells in BM and PB. The percentage of NK cells among nuclear cells and lymphocyte was significantly decreased and led to increased ratio of T and NK cells in BM and PB post‐G‐CSF in vivo application. Relative expansion of CD56bri NK cells led to a decreased ratio of CD56dim and CD56bri NK subsets in BM and PB post‐G‐CSF in vivo application. The expression of CD62L, CD54, CD94, NKP30 and CXCR4 on NK cells was significantly increased in PB after G‐CSF treatment. G‐CSF treatment decreased the IFN‐γ‐secreting NK population (NK1) dramatically in BM and PB, but increased the IL‐13‐secreting NK (NK2), TGF‐β‐secreting NK (NK3) and IL‐10‐secreting NK (NKr) populations significantly in BM. Clinical data demonstrated that higher doses of NK1 infused into the allograft correlated with an increased incidence of chronic graft‐vs‐host disease post‐transplantation. Taken together, our results show that the in vivo application of G‐CSF can modulate NK subpopulations, leading to an increased ratio of T and NK cells and decreased ratio of CD56dim and CD56bri NK cells as well as decreased NK1 populations in both PB and BM.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Effect of the in vivo application of granulocyte colony‐stimulating factor on NK cells in bone marrow and peripheral blood

Han

et al. 2018

J Cellular Molecular Medi

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“…In contrast, recent studies of T-replete G-CSFstimulated haploidentical BMT have reported up to 70% cGVHD (and nearly 50% extensive cGVHD) in both adults and children. 41 Recent series of nsTCD haploidentical HSCT have reported significant rates of late TRM in both children and adults, predominantly from delayed T-cell immune reconstitution and viral infections, resulting in overall TRM of 40% to 60%. 4,40,42,43 In contrast we saw no significant morbidity or mortality related to viral infection and no TRM beyond 6 months post-BMT.…”

Section: Discussionmentioning

confidence: 99%

Outcome of alloanergized haploidentical bone marrow transplantation after ex vivo costimulatory blockade: results of 2 phase 1 studies

Davies

Gribben

Brennan

et al. 2008

Blood

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“…All patients achieved complete donor chimerism. [4][5][6] On the other hand, PBSC is becoming popular in the allotransplant setting because of faster engraftment, [7][8][9] and recent studies showing durable engraftment using PBSCT even in haploidentical HSCT. 10,11 Aversa et al 10 report that using a megadose of CD34 þ cells selected by CliniMacs (Miltenyi Biotech, Bergisch Gladloach, Germany) from G-PB, together with highly immunosuppressive and myeloablative conditioning, resulted in a high incidence of durable engraftment in haploidentical HSCT; the reported engraftment rate is 91%.…”

Section: Introductionmentioning

confidence: 99%

The inferiority of G-PB to rhG-CSF-mobilized blood and marrow grafts as a stem cell source in patients with high-risk acute leukemia who underwent unmanipulated HLA-mismatched/haploidentical transplantation: a comparative analysis

et al. 2009

Bone Marrow Transplant

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The purpose of this study was to investigate the efficacy and feasibility of unmanipulated haploidentical PBSCT for the treatment of acute leukemia (AL). This study compares the clinical outcomes of high-risk AL patients who received PBSCs harvested from family members sharing at least one common haplotype to outcomes of high-risk AL patients who received a mixture of G-CSFprimed BM (G-BM) and peripheral blood (G-PB) harvests. The results show that PBSCT achieved inferior cumulative myeloid engraftment at 30 days after transplant (89.9 ± 10.1% vs 100%; P ¼ 0.04), with lower cumulative incidence of grade II-IV acute GVHD (aGVHD) (37.1 ± 16.5% vs 63.2 ± 6%; P ¼ 0.058) compared with G-BM/G-PB transplant. However, both transplant protocols had similar rates of 2-year relapse (29.6±17.1% vs 34.0±5.7%; P ¼ 0.954), and PBSCT produced a higher incidence of 2-year non-leukemic mortality (62.5 ± 14.8% vs 35.1 ± 5.1%; P ¼ 0.014), as well as lower rates of overall (26.8±12.3% vs 43.2 ± 5.0%; P ¼ 0.052) and disease-free survival (26.8 ± 12.3% vs 42.4 ± 5.0%; P ¼ 0.071) compared with G-BM/G-PB transplant. These results suggest that haploidentical HSCT is an option for patients with AL who urgently need a graft and do not have matched sibling donors. PBSCT is potentially inferior to G-BM/G-PB transplant, and improvements should be made before PBSCT becomes a routine in unmanipulated mismatched/ haploidentical transplant settings.

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Haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion for the treatment of hematological malignancies

Cited by 369 publications

References 18 publications

Effect of the in vivo application of granulocyte colony‐stimulating factor on NK cells in bone marrow and peripheral blood

Effect of the in vivo application of granulocyte colony‐stimulating factor on NK cells in bone marrow and peripheral blood

Outcome of alloanergized haploidentical bone marrow transplantation after ex vivo costimulatory blockade: results of 2 phase 1 studies

The inferiority of G-PB to rhG-CSF-mobilized blood and marrow grafts as a stem cell source in patients with high-risk acute leukemia who underwent unmanipulated HLA-mismatched/haploidentical transplantation: a comparative analysis

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