Successful early unmanipulated haploidentical transplantation with reduced-intensity conditioning for primary graft failure after cord blood transplantation in hematologic malignancy patients

Tang, Baolin; Zhu, Xiaoyu; Zheng, Changcheng; Liu, H L; Geng, Li; Wang, X B; Ding, Kaiyang; Yao, Wen; Tong, Juan; Song, Kaidi; Zhang, L; Qiang, Ping; Sun, Zimin

doi:10.1038/bmt.2014.250

Cited by 17 publications

(6 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the current study, we demonstrated that a transplantation with a reduced-intensity fludarabine and cyclophosphamide (Flu/Cy) conditioning regimen from different HIDs provides a very successful salvage for patients with GF after stem cell transplantation. Previous reports of salvage haploidentical stem cell transplantation were of small patient populations and case series, and importantly, most were retrospective and heterogenous in terms of conditioning regimens and protocol (13)(14)(15)(16)(17)(18)(19)(20)(21). To the best of our knowledge, this is the first prospective study investigating salvage haploidentical transplantation in patients with GF.…”

Section: Discussionmentioning

confidence: 98%

Graft Failure in Patients With Hematological Malignancies: A Successful Salvage With a Second Transplantation From a Different Haploidentical Donor

Sun

Wang

et al. 2021

Front. Med.

View full text Add to dashboard Cite

Graft failure (GF) is a fatal complication of allogeneic stem cell transplantation, especially after haploidentical transplantation. The mortality of GF is nearly 100% without an effective salvage method. A second transplantation is usually necessary to save the patient's life. However, there is no standardized regimen, and the outcome is usually disappointing. We report on a prospective single-center study using a reduced-intensity conditioning regimen with different haploidentical donors (HIDs). Patients with GF after the first transplantation were enrolled in a prospective single-arm clinical trial (ClinicalTrials.Gov ID: NCT03717545) at the Peking University Institute of Hematology. The conditioning regimen consisted of fludarabine (30 mg/m2) (days−6 to−2) and cyclophosphamide (1,000 mg/m2/day) (days−5 to−4). Patients underwent a second transplant from a different HID using a granulocyte colony-stimulating factor primed bone marrow and peripheral blood stem cells. The primary outcome was neutrophil engraftment at day 28. The secondary outcomes included platelet engraftment at day 100, transplant-related mortality (TRM) at day 30, TRM at day 100, and overall survival (OS) at 1 year. From March 2018 to June 2020, 13 patients were enrolled in this clinical trial. Of the 13 patients, five had acute myeloid leukemia, five had acute lymphoblastic leukemia, two had myelodysplastic syndromes, and one had a non-Hodgkin lymphoma. The median age at first transplantation was 38 years (range, 8–55 years). As for the first transplantation, 11 patients underwent haploidentical transplantations and two underwent unrelated donor transplantations. At the time of GF, three patients had complete donor chimerism, five had mixed chimerism, and five had complete recipient chimerism. The median time from the first transplantation to the second transplantation was 49 (range 35–120) days. The medians of infused cell doses were as follows: mononuclear cells 7.93 (5.95–12.51) × 108/kg and CD34 + cells 2.28 (0.75–5.57) × 106/kg. All 13 patients achieved neutrophil engraftment after the second transplantation, with a median engraftment time of 11 (range 10–20) days after transplantation. The platelet engraftment rate on day 100 after transplantation was 76.9%. The TRMs at day 30, day 100, and 1-year were 0, 0, and 23.1%, respectively. The OS and disease-free survival at 1-year were 56.6 and 48.4%, respectively. For patients with GF after first transplantation, a second transplantation using a fludarabine/cyclophosphamide regimen from a different HID was a promising salvage option. Further investigation is needed to confirm the suitability of this method.

show abstract

Section: Discussionmentioning

confidence: 98%

Graft Failure in Patients With Hematological Malignancies: A Successful Salvage With a Second Transplantation From a Different Haploidentical Donor

Sun

Wang

et al. 2021

Front. Med.

View full text Add to dashboard Cite

show abstract

“…Bojic et al [14] reported 7 patients transplanted with umbilical cord blood for primary graft failure, all achieving full donor engraftment, but 4 patients were alive after 29 months. Tang et al [15] reported 17 cord blood graft failure patients who were treated with unmanipulated haploidentical transplant showing a 1-year OS of 64.7%. However, the median age of this cohort was 11 years, whereas in ours it was 47 years.…”

Section: Discussionmentioning

confidence: 99%

Outcomes of Salvage Haploidentical Transplant with Post-Transplant Cyclophosphamide for Rescuing Graft Failure Patients: a Report on Behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy

Prata

Resche‐Rigon

Blaise

et al. 2019

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

Prognosis of patients with graft failure is dismal, and retransplantation is the sole option for long-term survival. To address the interest of haploidentical transplantation as a salvage option in this context, we analyzed data from 24 patients with graft failure or loss retransplanted with a haploidentical donor who received post-transplant cyclophosphamide (PTCy) as graft-versus-host disease prophylaxis (GVHD). Fludarabine-based reduced-intensity conditioning was used in 23 patients and the Baltimore regimen in 14 patients. The median delay between previous and salvage transplantation for graft failure was 63 days (range, 39 to 98). In addition to PTCy, all patients received cyclosporine, and 22 patients also received mycophenolate mofetil for GVHD prophylaxis. With a median followup of 353 days (range, 16 to 2010), 1-year overall survival (OS) was 56% (95% confidence interval, 38% to 81%). Transplant complications accounted for 80% of deaths. The cumulative incidence of neutrophil engraftment at day +30 was 79%. Cumulative incidence of grades II to IV acute GVHD at day 100 was 14%, and 1-year cumulative incidence of chronic GVHD was 31%. One-year cumulative incidence of relapse was 13%. Stem cell source did not impact on engraftment, GVHD, relapse, or OS. Salvage haploidentical transplant with PTCy for rescuing graft failure patients leads to an acceptable 1-year OS and might be a valid option in this poor situation.

show abstract

“…The cumulative incidences of grade III–IV acute GVHD and chronic GVHD were 17.6% and 29.4%, respectively. TRM at 180 days was 29.4%, and the probability of 3‐year leukemia‐free survival was 57.5% . In the present study of pediatric patients, all recipients except one who died early achieved neutrophil engraftment within 16 days and established rapid donor chimerism after the second TCR‐haploidentical HSCT.…”

Section: Discussionmentioning

confidence: 54%

“…Yet, relatively high rates of TRM after salvage CB transplantation have been reported in both adult and pediatric cases . Another possible approach is a haploidentical HSCT from family members, and some recent reports have shown the usefulness of TCR‐haploidentical HSCT as salvage therapy for GFs . However, to date, little information is available regarding second TCR‐haploidentical HSCT for pediatric patients with primary GF.…”

Section: Introductionmentioning

confidence: 99%

T cell replete–haploidentical second hematopoietic stem cell transplantation for primary graft failure in pediatric patients with hematologic malignancies

Mochizuki

Sano

Akaihata

et al. 2017

Pediatric Transplantation

View full text Add to dashboard Cite

GF is one of the fatal complications of allogeneic HSCT. To rescue patients with primary GF, a second HSCT should be conducted as soon as possible, but the optimal donor source and technique have yet to be established. In this study, we retrospectively analyzed six children with hematologic malignancies who received TCR-haploidentical second HSCT for primary GF. The median interval between the prior HSCT and the second HSCT was 37.5 days. All patients received fludarabine and ATG containing reduced-intensity re-conditioning before the second HSCT. All patients, except one who died early, achieved both neutrophil and Plt engraftment at a median time of 15 and 33 days, respectively. Chimerism analysis showed that all engrafted patients achieved complete donor chimerism within 3 weeks. Four patients developed acute GVHD, and three patients developed chronic GVHD. TRM occurred in two patients. Median follow-up of the four survivors was 6.8 years, and all remained in sustained remission until the last follow-up. These results suggested that a TCR-haploidentical second HSCT for pediatric patients is feasible, and this approach may provide a potent option for children with primary GF.

show abstract

Successful early unmanipulated haploidentical transplantation with reduced-intensity conditioning for primary graft failure after cord blood transplantation in hematologic malignancy patients

Cited by 17 publications

References 29 publications

Graft Failure in Patients With Hematological Malignancies: A Successful Salvage With a Second Transplantation From a Different Haploidentical Donor

Graft Failure in Patients With Hematological Malignancies: A Successful Salvage With a Second Transplantation From a Different Haploidentical Donor

Outcomes of Salvage Haploidentical Transplant with Post-Transplant Cyclophosphamide for Rescuing Graft Failure Patients: a Report on Behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy

T cell replete–haploidentical second hematopoietic stem cell transplantation for primary graft failure in pediatric patients with hematologic malignancies

Contact Info

Product

Resources

About