Comparison of the outcomes after haploidentical and cord blood salvage transplantations for graft failure following allogeneic hematopoietic stem cell transplantation

Harada, Kaito; Fuji, Shigeo; Seo, Sachiko; Kanda, Junya; Ueki, Tomoyuki; Kimura, Fumihiko; Katô, Kôji; Uchida, Naoyuki; Ikegame, Kazuhiro; Onizuka, Makoto; Matsuoka, Ken‐ichi; Doki, Noriko; Kawakita, Toshiro; Onishi, Yasushi; Yano, Shingo; Fukuda, Takahiro; Takanashi, Minoko; Kanda, Yoshinobu; Atsuta, Yoshiko; Ogata, Masao

doi:10.1038/s41409-020-0821-9

Cited by 20 publications

(12 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CB and HIDs are alternative choices. A recent Japanese study demonstrated the engraftment advantage of an HID over CB (22). Beyond that, the HID has several other advantages, such as wide availability of multiple donors and sufficient cell number.…”

Section: Discussionmentioning

confidence: 99%

“…Because a second transplantation is usually performed soon after the first transplantation, reconditioning might lead to significant accumulative organ toxicities and TRM. It has been demonstrated that a reduced-intensity conditioning regimen is associated with favorable outcomes in previous reports (22,23). Thus, while a reduced-intensity conditioning regimen is generally recommended for second transplantation, there is no standard conditioning regimen.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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: 99%

Section: Discussionmentioning

confidence: 99%

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

“…Ma et al ( 30 ) analyzed the outcomes of PBSCT alone with ATG/G-CSF and found that the cumulative incidences of grade II–IV aGVHD at day 100, grade III–IV aGVHD at day 100, cGVHD at one year, and moderate/severe cGVHD at 1 year were 29.9%, 7.5%, 54.9%, and 17.4%, respectively, which were higher than those in our haplo-cord-PBSCT group, especially in cGVHD incidence. A possible explanation of these results could be that UCB may regulate the hematopoietic microenvironment and reduce immune rejection ( 37 ). However, compared with haplo-cord-PBSCT in our study, other studies showed lower cumulative incidences of 100-day aGVHD (20.0%–27.0%) and 1-year cGVHD (20.0%–27.0%) in haplo-cord-HSCT ( 17 , 19 , 20 ).…”

Section: Discussionmentioning

confidence: 99%

Comparison of Outcomes of Haploidentical Peripheral Blood Stem Cell Transplantation Supported by Third-Party Cord Blood Versus Human Leukocyte Antigen-Matched Sibling Peripheral Blood Stem Cell Transplantation in Hematologic Malignancy Patients

et al. 2022

View full text Add to dashboard Cite

Recent studies have shown that haploidentical hematopoietic stem cell transplantation supported by third-party cord blood (haplo-cord-HSCT) results in rapid hematopoietic recovery, low incidences of graft-versus-host disease (GVHD), and relapse of hematologic malignancies. However, few reports on haploidentical peripheral blood stem cell transplantation supported by third-party cord blood (haplo-cord-PBSCT) have been published. To evaluate the outcomes of patients who underwent haplo-cord-PBSCT or human leukocyte antigen (HLA)-matched sibling donor peripheral blood stem cell transplantation (MSD-PBSCT), we retrospectively reviewed the clinical data of patients with hematologic malignancies who underwent haplo-cord-PBSCT (n = 93) or MSD-PBSCT (n = 72) in our hospital from March 2017 to December 2020. In the haplo-cord-PBSCT and MSD-PBSCT groups, the median time for neutrophil and platelet engraftment was 13 vs. 12 days (p = 0.07) and 16 vs. 13 days (p = 0.06), respectively. The 30-day cumulative incidences of neutrophil engraftment were 100.0% and 98.6% (p = 0.12). The 100-day cumulative incidences of platelet engraftment were 96.8% and 98.6% (p = 0.01). The 100-day cumulative incidences of grade II–IV and grade III–IV acute GVHD were 29.1% vs. 23.6% (p = 0.42) and 9.7% vs. 4.2% (p = 0.18). The cumulative incidences of total and moderate/severe chronic GVHD at 1 year were 26.5% vs. 17.4% and 8.1% vs. 4.5%, respectively, and at 3 years were 34.7% vs. 34.3% (p = 0.60) and 13.6% vs. 10.6% (p = 0.49), respectively. The cumulative incidences of relapse at 1 year were 9.3% and 7.2% and at 3 years were 17.0% and 17.0% (p = 0.98). Non-relapse mortality (NRM) at 1 year was 14.6% and 8.6% and at 3 years was 17.4% and 8.6% (p = 0.13) in two groups. The probabilities of overall survival (OS), disease-free survival (DFS), and GVHD-free/relapse-free survival (GRFS) at 1 year were 81.7% vs. 88.6%, 76.1% vs. 84.2%, and 71.7% vs. 79.7%, respectively, and at 3 years were 78.7% vs. 79.0%, 65.6% vs. 74.4%, and 55.5% vs. 63.6%, respectively, in the corresponding group, p > 0.05. In conclusion, for patients with acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) and acute lymphoid leukemia (ALL), haplo-cord-PBSCT results in similar outcomes compared with MSD-PBSCT, and it may be a valid alternative transplantation method.

show abstract

“…However, this interpretation should be cautious, because a considerable number of patients probably had no choice but to receive growth factor due to their comorbidities. As a salvage therapy for GF, Harada et al 22 reported outcomes of salvage haploidentical HCT was associated with better ANC recovery and lower NRM compared with cord blood graft HCT. Rudakova et al 23 reported a 48% response and prolonged survival with thrombopoietin agonists in GF after HCT.…”

Section: Discussionmentioning

confidence: 99%

Incidence, Management, and Prognosis of Graft Failure and Autologous Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

Park

Lee

et al. 2021

J Korean Med Sci

View full text Add to dashboard Cite

Background This study presents outcomes of management in graft failure (GF) after allogeneic hematopoietic stem cell transplantation (HCT) and provides prognostic information including rare cases of autologous reconstitution (AR). Methods We analyzed risk factors and outcomes of primary and secondary GF, and occurrence of AR in 1,630 HCT recipients transplanted over period of 18 years (January 2000–September 2017) at our center. Results Primary and secondary GF occurred in 13 (0.80%), and 69 patients (10-year cumulative incidence, 4.5%) respectively. No peri-transplant variables predicted primary GF, whereas reduced intensity conditioning (RIC) regimen (relative risk [RR], 0.97–28.0, P < 0.001) and lower CD34 + cell dose (RR, 2.44–2.84, P = 0.002) were associated with higher risk of secondary GF in multivariate analysis. Primary GF demonstrated 100% mortality, in the secondary GF group, the 5-year Kaplan-Meier survival rate was 28.8%, relapse ensued in 18.8%, and AR was observed in 11.6% (n = 8). In survival analysis, diagnosis of aplastic anemia (AA), chronic myeloid leukemia and use of RIC had a positive impact. There were 8 patients who experienced AR, which was rarely reported after transplantation for acute leukemia. Patient shared common characteristics such as young age (median 25 years), use of RIC regimen, absence of profound neutropenia, and had advantageous survival rate of 100% during follow period without relapse. Conclusion Primary GF exhibited high mortality rate. Secondary GF had 4.5% 10-year cumulative incidence, median onset of 3 months after HCT, and showed 5-year Kaplan-Meier survival of 28.8%. Diagnosis of severe AA and use of RIC was both associated with higher incidence and better survival rate in secondary GF group. AR occurred in 11.6% in secondary GF, exhibited excellent prognosis.

show abstract

Comparison of the outcomes after haploidentical and cord blood salvage transplantations for graft failure following allogeneic hematopoietic stem cell transplantation

Cited by 20 publications

References 42 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

Comparison of Outcomes of Haploidentical Peripheral Blood Stem Cell Transplantation Supported by Third-Party Cord Blood Versus Human Leukocyte Antigen-Matched Sibling Peripheral Blood Stem Cell Transplantation in Hematologic Malignancy Patients

Incidence, Management, and Prognosis of Graft Failure and Autologous Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

Contact Info

Product

Resources

About