Donor KIR2DS1-Mediated Decreased Relapse and Improved Survival Depending on Remission Status at HLA-Haploidentical Transplantation with Post-Transplantation Cyclophosphamide

Ido, Kentaro; Koh, Hideo; Hirose, Asao; Okamura, Hiroshi; Koh, Shiro; Nanno, Satoru; Nishimoto, Mitsutaka; Nakamae, Mika; Nakashima, Yasuhiro; Nakane, Takahiko; Hino, Masayuki; Nakamae, Hirohisa

doi:10.1016/j.bbmt.2019.12.765

Cited by 8 publications

(10 citation statements)

References 49 publications

(80 reference statements)

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“…Patients who were enrolled in the clinical studies at our institute received the following conditioning regimen [14,[21][22][23]: the intravenous busulfan (Bu)-based conditioning regimen consisted of 15 mg/m 2 fludarabine and 2,000 mg/m 2 cytarabine twice a day on days -11 and -10, 30 mg/m 2 fludarabine once a day on days -6 to -3 and 0.8 mg/kg Bu 4 times a day on days -6 to -3. The melphalan (Mel)-based conditioning regimen replaced Bu with 100 mg/m 2 Mel once a day on day -2.…”

Section: Patients Donors and Transplantation Proceduresmentioning

confidence: 99%

“…Relapse/progression was defined as the first point at which hematological or pathological evidence of relapse/progression of primary disease was detected after PT/Cy-haplo. [21]…”

Section: Definitionsmentioning

confidence: 99%

“…Multivariable analyses were performed using the donor rs1049174 polymorphism and other previously reported donor-related risk factors (Table 3). [21,24,40] Several models limiting the degree of freedom were constructed to stabilize each model [38,41,42], although the low number of NRM events was intolerable for most of the models (23 events in the entire population). In the patients who received PT/Cy-haplo with ATG, no donor-related factors were associated with the risk of relapse/progression, NRM or the OS.…”

Section: Stratified By Gvhd Prophylaxismentioning

confidence: 99%

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Effect of Donor NKG2D Polymorphism on Relapse after Haploidentical Transplantation with Post-Transplantation Cyclophosphamide

Ido

Koh

Hirose

et al. 2022

Transplantation and Cellular Therapy

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Section: Patients Donors and Transplantation Proceduresmentioning

confidence: 99%

“…Relapse/progression was defined as the first point at which hematological or pathological evidence of relapse/progression of primary disease was detected after PT/Cy-haplo. [21]…”

Section: Definitionsmentioning

confidence: 99%

Section: Stratified By Gvhd Prophylaxismentioning

confidence: 99%

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Effect of Donor NKG2D Polymorphism on Relapse after Haploidentical Transplantation with Post-Transplantation Cyclophosphamide

Ido

Koh

Hirose

et al. 2022

Transplantation and Cellular Therapy

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“…27,28 More recently, Ido et al reported that KIR2DS1 positivity significantly reduced the risk of both relapse and mortality in the complete response (CR) group, but not in the non-CR group, after PTCy-haploHSCT. 29 Although patients with a high residual tumor burden require earlier exertion of graft vs. leukemia (GVL) effects to control leukemia/tumor progression, PTCy eliminates proliferating alloreactive NK cells and NK cell recovery may require more than 60 days. 21,22 These findings regarding immune reconstitution may explain why GVL effects mediated by NK cells were observed when the tumor burden was low.…”

Section: Natural Killer (Nk) Cell Reconstitutionmentioning

confidence: 99%

Immune reconstitution after T-cell replete HLA haploidentical hematopoietic stem cell transplantation using high-dose post-transplant cyclophosphamide

Maeda

2021

J Clin Exp Hematopathol

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As HLA haploidentical related donors are quickly available, HLA haploidentical hematopoietic stem cell transplantation (haploHSCT) using high-dose post-transplant cyclophosphamide (PTCy) is now widely used. Recent basic and clinical studies revealed the details of immune reconstitution after T-cell replete haploHSCT using PTCy. T cells and NK cells in the graft proliferate abundantly at day 3 post-haploHSCT, and the PTCy eliminates these proliferating cells. After ablation of proliferating mature cells, donor-derived NK cell reconstitution occurs after the second week; however, recovering NK cells remain functionally impaired for at least several months after haploHSCT. PTCy depletes proliferating cells, resulting in the preferential accumulation of Treg and CD4+ T cells, especially the memory stem T cell (T SCM ) phenotype. T SCM capable of both self-renewal and differentiation into effector T cells may play an important role in the first month of immune reconstitution. Subsequently, de novo T cells progressively recover but their levels remain well below those of donor CD4+ T cells at the first year after haploHSCT. The phenotype of recovering T cells after HSCT is predominantly effector memory, whereas B cells are predominantly phenotypically naive throughout the first year after haploHSCT. B cell recovery depends on de novo generation and they are not detected until week 4 after haploHSCT. At week 5, recovering B cells mostly exhibit an unconventional transitional cell phenotype and the cell subset undergoes maturation. Recent advances in immune reconstitution have improved our understanding of the relationship between haploHSCT with PTCy and the clinical outcome.

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“…It was also shown, in a murine model, that PTCy profoundly decreased graft-versus-leukemia (GVL) effects and that it could lead to rapid relapse 7 . Furthermore, the alloreactivity of natural killer (NK) cells plays a crucial role in the GVL effects after PTCy-haplo 8 – 11 ; however, the posttransplant recovery of NK cells may be suppressed by PTCy, suggesting that PTCy may reduce the GVL effects mediated by NK cells in the PTCy-haplo setting 11 .…”

Section: Introductionmentioning

confidence: 99%

A Prospective Study of an HLA-Haploidentical Peripheral Blood Stem Cell Transplantation Regimen Based on Modification of the Dose of Posttransplant Cyclophosphamide for Poor Prognosis or Refractory Hematological Malignancies

et al. 2022

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The optimal dose of posttransplant cyclophosphamide (PTCy) for use in patients undergoing HLA-haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide (PTCy-haplo) has not been sufficiently examined. This study evaluates the safety and efficacy of HLA-haploidentical hematopoietic cell transplantation with a reduced dose of PTCy for patients with a poor prognosis or those with refractory hematological malignancies. We conducted a prospective clinical study of PTCy-haplo with peripheral blood stem cells (PBSCs) using a modified PTCy dosage regimen consisting of 50 mg/kg on day 3 posttransplantation and a reduced dose of 25 mg/kg on day 4. The cumulative incidences of grades II to III and IV acute graft-versus-host disease (GVHD) at day 100 posttransplantation were 30% and 0%, respectively. The cumulative incidence of moderate-to-severe chronic GVHD after transplantation was 7.0%. The cumulative incidence of nonrelapse mortality at 1 year posttransplantation was 6.1%. Overall survival (OS) at 1 year was 66%. In addition, the restricted cubic-spline Cox regression analysis showed nonlinear relationship between the number of infused CD34+ cells and CD3+ cells, and OS. A graft composition of >4.54 × 106/kg CD34+ cells and >1.85 × 108/kg but ≤3.70 × 108/kg CD3+ cells was significantly associated with better survival, irrespective of the disease status (hazard ratio, 0.13; 95% confidence interval, 0.04–0.41; P < 0.001). These results suggest that PTCy-haplo with PBSCs using a de-escalated dose of 50 mg/kg on day 3 and 25 mg/kg on day 4 posttransplantation is a feasible option.

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Donor KIR2DS1-Mediated Decreased Relapse and Improved Survival Depending on Remission Status at HLA-Haploidentical Transplantation with Post-Transplantation Cyclophosphamide

Cited by 8 publications

References 49 publications

Effect of Donor NKG2D Polymorphism on Relapse after Haploidentical Transplantation with Post-Transplantation Cyclophosphamide

Effect of Donor NKG2D Polymorphism on Relapse after Haploidentical Transplantation with Post-Transplantation Cyclophosphamide

Immune reconstitution after T-cell replete HLA haploidentical hematopoietic stem cell transplantation using high-dose post-transplant cyclophosphamide

A Prospective Study of an HLA-Haploidentical Peripheral Blood Stem Cell Transplantation Regimen Based on Modification of the Dose of Posttransplant Cyclophosphamide for Poor Prognosis or Refractory Hematological Malignancies

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