Rescue haploidentical peripheral blood stem cell transplantation for engraftment failure: a single‐centre case series

Kliman, David; Bilmon, Ian; Kwan, John; Blyth, Emily; Micklethwaite, Kenneth; Panicker, Shyam; Bhattacharyya, Abir K.; Deren, Stephanie; Antonenas, Vicki; Huang, Guozhong; Gottlieb, David

doi:10.1111/imj.13979

Cited by 7 publications

(3 citation statements)

References 19 publications

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“…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.

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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.

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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.

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“…Although different donor sources have been used for rescue HSCT after GF [ 58 ] , transplantation from an immediately available donor is the optimal therapeutic option. Shortening the delay in donor procurement is of particular importance.…”

Section: Discussionmentioning

confidence: 99%

Graft failure after allogeneic hematopoietic stem cell transplantation in pediatric patients with acute leukemia: autologous reconstitution or second transplant?

Rostami,

Mirhosseini

et al. 2024

Stem Cell Res Ther

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Background Graft failure (GF) is a rare but serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). Prevention of graft failure remains the most advisable approach as there is no clear recommendation for the best strategies for reversing this complication. Administration of growth factor, additional hematopoietic progenitor boost, or a salvage HSCT are current modalities recommended for the treatment of GF. Autologous recovery without evidence of disease relapse occurs rarely in patients with GF, and in the absence of autologous recovery, further salvage transplantation following a second conditioning regimen is a potential treatment option that offers the best chances of long-term disease-free survival. The preconditioning regimens of second HSCT have a significant impact on engraftment and outcome, however, currently there is no consensus on optimal conditioning regimen for second HSCT in patients who have developed GF. Furthermore, a second transplant from a different donor or the same donor is still a matter of debate. Observations We present our experience in managing pediatric patients with acute leukemia who encountered graft failure following stem cell transplantation. Conclusions and relevance Although a second transplantation is almost the only salvage method, we illustrate that some pediatric patients with acute leukemia who experience graft failure after an allogeneic stem cell transplant using Myeloablative conditioning (MAC) regimen may achieve long-term disease-free survival through autologous hematopoiesis recovery.

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“…The conditioning regimens used for salvage transplantation were very heterogenous. The most frequently used conditioning regimens includes total nodal irradiation-based conditioning [22] and combination of udarabine, cyclophosphamide and low-dose total body irradiation (TBI) [16,23]. Gimamarco et al used a combination of udarabine 150mg/m 2 plus Cy 29mg/kg and TBI 2Gy, and the engraftment rate was 74% and 1-year TRM was 26% [16].…”

Section: Discussionmentioning

confidence: 99%

Salvage haploidentical transplantation for graft failure after first haploidentical allogeneic stem cell transplantation: an updated experience

Ma,

Zhu,

Zhang

et al. 2024

Bone Marrow Transplant

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Second transplantation was almost the only salvage for graft failure. However, there is no recommended regimens for second transplantation, especially in the haplo-SCT setting. We recently reported very encouraging outcomes using a novel method (salvage haploidentical transplantation from a different donor after conditioning with udarabine 30mg/m 2 from − 6d to -2d and cyclophosphamide 1g/m 2 from − 5d to -4d). Herein, we reported our updated experience in a total of 30 patients using this method. The median time of the second transplantation was 96.5 (33-215) days after the rst transplantation. Among the 30 patients, 2 used the same donor since there was no other donor available. One patient died before engraftment at 19 days after second transplantation. For the 29 evaluable patients, neutrophil engraftments were achieved in all (100%) patients at a median of 11 (8-24) days, while platelet engraftments were achieved in 22 (75.8%) patients at a median of 17.5 (9-140) days. The 1-year OS and DFS was 60% and 53.3%, respectively. CIR and TRM was 6.7% and 33.3%, respectively. Compared with historical group (n = 34), the neutrophil engraftment (100% versus 58.5%, p < 0.001) and platelet engraftment (75.8% versus 32.3%, p < 0.001) were signi cantly better in the novel regimen group, and the OS was also signi cantly improved (60.0% versus 26.4%, p = 0.011). In conclusion, salvage haploidentical transplantation from a different donor using Flu/Cy regimen represents a promising option to rescue patients with graft failure after the rst haploidentical stem cell transplantation.

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Rescue haploidentical peripheral blood stem cell transplantation for engraftment failure: a single‐centre case series

Cited by 7 publications

References 19 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

Graft failure after allogeneic hematopoietic stem cell transplantation in pediatric patients with acute leukemia: autologous reconstitution or second transplant?

Salvage haploidentical transplantation for graft failure after first haploidentical allogeneic stem cell transplantation: an updated experience

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