Similar incidence of severe acute GVHD and less severe chronic GVHD in PBSCT from unmanipulated, haploidentical donors compared with that from matched sibling donors for patients with haematological malignancies

Li, Honghua; Li, Fēi; Gao, Chunji; Huang, Wenrong; Jiang, Bo; Dou, Liping; Wang, Lili; Yu, Jie; Wang, Lu; Li, Wenjun; Yu, Li; Liu, Dai‐Hong

doi:10.1111/bjh.14331

Cited by 19 publications

(21 citation statements)

References 21 publications

(36 reference statements)

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“…The incidences of DLI-associated acute GVHD grades 2–4, 3–4, chronic GVHD, and NRM in our study were 55.3%, 10.2%, 52.0,%, and 33.1%, respectively. In the patients who received haplo-PBSCT in our unit before January of 2015 [ 14 ], the incidences of acute GVHD grades 2–4, 3–4, chronic GVHD, and NRM were 36.1%, 14.5%, 38.4%, and 24.0%, respectively. Though the incidences of GVHD between these two cohort studies should not be compared directly, it seemed that G-PB DLI did not result in an intolerable toxicity in terms of GVHD and NRM.…”

Section: Discussionmentioning

confidence: 99%

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Donor lymphocyte infusion for prevention of relapse after unmanipulated haploidentical PBSCT for very high-risk hematologic malignancies

et al. 2018

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Unmanipulated haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) has been an established treatment to cure high-risk leukemia/lymphoma. Relapse is the main cause of treatment failure for patients with relapsed/refractory disease or with very high-risk gene mutations such as TP53, TET2, and DNMT3a. In this study, we aimed to establish the tolerance and efficacy of prophylactic donor lymphocyte infusion (DLI) with G-CSF-primed peripheral blood progenitors for prevention of relapse in these very high-risk patients after haplo-PBSCT. The prophylactic DLI was given at a median of 77 days after transplantation in 31 of 45 consecutive patients with very high-risk leukemia/lymphoma. The median dose of CD3 cells for infusion was 1.8 × 10/kg. The 100-day incidences of acute graft-versus-host disease (GVHD) grades 2-4 and 3-4 after DLI were 55.3% and 10.2%. The 2-year incidences of chronic GVHD and severe chronic GVHD were 52.0% and 18.2%. The 2-year incidences of non-relapse mortality and relapse were 33.1% and 32.5%. The 2-year probabilities of overall survival and relapse-free survival were 40.1% and 31.9%. Poor-risk gene mutations (p = 0.029), disease in non-remission status prior to transplantation (p = 0.005), and donors older than 40 years of age (p = 0.043) were associated with relapse after DLI. In multivariate analysis, disease in non-remission status prior to transplantation was an independent risk factor of relapse (hazard ratio = 4.079; p = 0.035). These data showed the feasibility of the prophylactic DLI in the haplo-PBSCT setting and the anti-leukemic efficacy in very high-risk leukemia/lymphoma.

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Section: Discussionmentioning

confidence: 99%

“…All recipients received G-PB as a source of graft. The supportive therapy was done as previously described [ 14 ].…”

Section: Methodsmentioning

confidence: 99%

Donor lymphocyte infusion for prevention of relapse after unmanipulated haploidentical PBSCT for very high-risk hematologic malignancies

et al. 2018

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“…The incidence of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) antigenemia and EBV-associated post-transplantation proliferative disease (PTLD) was higher in patients receiving stem cells from haploidentical donors compared with that of patients receiving MSD-PBSCT. Donor age ≥ 40 years vs. younger donors was associated with a higher incidence of aGVHD grades 2-4 (P = 0.02) and treatment-related mortality (TRM) (P = 0.022) [4].…”

Section: Introductionmentioning

confidence: 99%

“…There is an urgent need to reduce the incidence of severe cGVHD and improve the quality of life in patients who have undergone MSD peripheral blood stem cell transplantation (MSD-PBSCT) [3]. We have reported that rabbit anti-thymocyte globulin (rATG) (Sanofi, Paris, France) may effectively and safely reduce the incidence and severity of cGVHD in patients receiving myeloablative conditioning before peripheral blood stem cell transplantation from haploidentical donors [4]. The 3-year cumulative incidence of extensive and severe cGVHD was 41.5% and 21.2% in patients receiving MSD-PBSCT (without rATG) compared with 17.1% (P = 0.017) and 5.8% (P = 0.049) in patients receiving stem cells from haploidentical donors [4].…”

Section: Introductionmentioning

confidence: 99%

“…We have reported that rabbit anti-thymocyte globulin (rATG) (Sanofi, Paris, France) may effectively and safely reduce the incidence and severity of cGVHD in patients receiving myeloablative conditioning before peripheral blood stem cell transplantation from haploidentical donors [4]. The 3-year cumulative incidence of extensive and severe cGVHD was 41.5% and 21.2% in patients receiving MSD-PBSCT (without rATG) compared with 17.1% (P = 0.017) and 5.8% (P = 0.049) in patients receiving stem cells from haploidentical donors [4]. Our ATG GVHD prophylaxis regimen in unmanipulated haploidentical PBSCT includes rATG given at a dose of 10 mg/kg over 4 days (days −5 to −2) before graft infusion.…”

Section: Introductionmentioning

confidence: 99%

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Reduced risk of chronic GVHD by low-dose rATG in adult matched sibling donor peripheral blood stem cell transplantation for hematologic malignancies

Dou

Hou

et al. 2019

Ann Hematol

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The optimal rabbit anti-thymocyte globulin (rATG) graft-versus-host disease (GVHD) prophylaxis regimen in matched sibling donor peripheral blood stem cell transplantation (MSD-PBSCT) remains to be elucidated. In this prospective study, we used lowdose rATG for GVHD prophylaxis in patients or donors aged ≥ 40 years with hematological malignancies receiving MSD-PBSCT. rATG was administered to 40 patients at an intravenous dose of 5 mg/kg divided over day 5 and day 4 before graft infusion. No graft failure occurred. Median times to leukocyte engraftment and platelet engraftment were 11.0 days and 13.9 days. The cumulative incidence of grades 2-4 and grades 3-4 acute GVHD at day +100 was 30.0% and 2.6%. The 2-year cumulative incidence of extensive chronic GVHD and severe chronic GVHD was 11.4% and 14.7%. 93.5% (29/31) of patients had discontinued immunosuppressive medication within 3 years after transplantation. The 2-year cumulative incidence of transplant-related mortality (TRM) and relapse was 14.0% and 22.6%. The cumulative incidence of cytomegalovirus reactivation, Epstein-Barr virus reactivation, and fungal infection was 22.3%, 12.9%, and 12.5%. Kaplan-Meier estimates for overall survival, disease-free survival, and GVHD-free and relapse-free survival 3 years after transplantation were 68.9%, 68.9%, and 54.0%. rATG for GVHD prophylaxis is tolerable and efficacious at a 5 mg/kg total dose administered over 2 days (days −5 to −4) in patients receiving allogeneic MSD-PBSCT.

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Targeted dosing of anti‐thymocyte globulin in adult unmanipulated haploidentical peripheral blood stem cell transplantation: A single‐arm, phase 2 trial

Wang,

Wang

et al. 2023

American J Hematol

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Anti‐thymocyte globulin (ATG) is widely used in allogeneic hematopoietic stem cell transplantation to prevent severe graft‐versus‐host disease (GVHD) and graft failure. However, overexposure to ATG may increase cytomegalovirus (CMV), Epstein‐Barr virus (EBV) reactivation, non‐relapse mortality, and disease recurrence. To investigate the optimal dosing of ATG, we established a targeted dosing strategy based on ATG concentration monitoring for haploidentical peripheral blood stem cell transplantation (haplo‐PBSCT). The aim of this phase 2 trial is to evaluate the safety and efficacy of the ATG‐targeted dosing strategy in adult unmanipulated haplo‐PBSCT. ATG was administered for 4 days (−5 days to −2 days) during conditioning. The ATG doses on −3 days and −2 days were adjusted by our dosing strategy to achieve the optimal ATG exposure. The primary endpoint was CMV reactivation on +180 days. Between December 2020 and January 2022, 66 haplo‐PBSCT patients were enrolled and 63 of them were evaluable with a median follow‐up of 632 days. The cumulative incidence of CMV reactivation was 36.7% and that of EBV was 58.7%. The 1‐year disease‐free survival was 82.5%, overall survival was 92.1%, and CD4+ T‐cell reconstruction on +100 days was 76.8%. The most common severe regimen‐associated toxicities (> grade 3) were infections (51.5%) and gastrointestinal toxicity (25.5%). A total of 102 haplo‐PBSCT patients who received the conventional fixed ATG dose (cumulative 10 mg/kg) comprised historical control. The outcomes in historical control were inferior to those of phase 2 trial cohort (CMV reactivation: 70.8%, p < .001; EBV reactivation: 76.0%, p = .024; CD4 + T‐cell reconstruction: 54.1%, p = .040). In conclusion, ATG‐targeted dosing strategy reduced CMV/EBV reactivation and improved survival without increasing GVHD after haplo‐PBSCT. These advantages may be associated with accelerated immune reconstitution.

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Similar incidence of severe acute GVHD and less severe chronic GVHD in PBSCT from unmanipulated, haploidentical donors compared with that from matched sibling donors for patients with haematological malignancies

Cited by 19 publications

References 21 publications

Donor lymphocyte infusion for prevention of relapse after unmanipulated haploidentical PBSCT for very high-risk hematologic malignancies

Donor lymphocyte infusion for prevention of relapse after unmanipulated haploidentical PBSCT for very high-risk hematologic malignancies

Reduced risk of chronic GVHD by low-dose rATG in adult matched sibling donor peripheral blood stem cell transplantation for hematologic malignancies

Targeted dosing of anti‐thymocyte globulin in adult unmanipulated haploidentical peripheral blood stem cell transplantation: A single‐arm, phase 2 trial

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