Donor cell-derived hematological malignancy: a survey by the Japan Society for Hematopoietic Cell Transplantation

Kato, Motohiro; Yamashita, Takuya; Suzuki, Ritsuro; Matsumoto, Kimikazu; Nishimori, Hisakazu; Takahashi, Satoshi; Iwato, Koji; Nakaseko, Chiaki; Kondo, Tadakazu; Imada, Kazunori; Kimura, Fumihiko; Ichinohe, Tatsuo; Hashii, Yoshiko; Kato, Kazushige; Atsuta, Yoshiko; Taniguchi, Satoshi; Fukuda, Takahiro

doi:10.1038/leu.2016.23

Cited by 42 publications

(37 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is difficult to compare these results to the literature because 1) there is little reported cumulative incidence data; 2) the competing risks are not always specified and thus might be different than the ones included in our model and 3) registry and survey data is more limited than institutional data. Although our estimated cumulative incidence of DDM appears higher than in the Japanese survey study 17 , the authors did not include relapse as a competing risk in their cumulative incidence analysis, making a direct comparison impossible. It will be important to compare the estimated cumulative incidence of DDM after PTCy with other studies as they are reported in the future.…”

Section: Discussionmentioning

confidence: 78%

“…A total of 36,870 allogeneic transplants with engraftment were registered in the Japan Society for Hematopoietic Cell transplantation registry and forty cases of donor cell leukemia were identified at a median of 22 months after BMT, with a higher cumulative incidence after cord blood transplant of 0.35%, and an association with older donors 17 . The second largest study of DDM was an analysis of donor cell leukemia in Europe during a 20 year period.…”

Section: Discussionmentioning

confidence: 99%

“…In the first prospective search for donor derived leukemias, the authors conclude that the real incidence of this complication has been underestimated 18 . Cases have been reported with all stem cell sources, including peripheral blood stem cells (PBSC) 13, 21, 22 , bone marrow (BM) 13, 21, 23 , or umbilical cord blood (UCB) 16, 21, 24-26 , with related 13 and unrelated donors 27 , as well as after both myeloablative or reduced intensity conditioning regimens 14, 17 .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Post-Transplantation Cyclophosphamide after Bone Marrow Transplantation Is Not Associated with an Increased Risk of Donor-Derived Malignancy

Majzner

Mogri

Varadhan

et al. 2017

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

Post-transplant cyclophosphamide (PTCy) can be used for graft versus host disease (GVHD) prophylaxis alone or in combination with other agents and is associated with excellent rates of engraftment, acute and chronic GVHD, and an absence of post-transplant lymphoproliferative disease. No study has previously evaluated the risk for developing donor derived malignancy (DDM) in patients who receive PTCy. Giving chemotherapy in the immediate post-transplant period carries with it a theoretic risk of disturbing the graft at a time of increased hematopoietic stress and causing or accelerating the development of malignancy. From 2000-2011, 789 patients underwent allogeneic transplant and received PTCy at the Johns Hopkins Hospital. There were four cases of DDM identified among this large population, which is similar to or below the rate of DDM published in the literature. We found that the estimated cumulative incidence by competing risk analysis of DDM is 1.4% (standard error=1.02%). The use of PTCy does not appear to increase the risk of DDM.

show abstract

Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Post-Transplantation Cyclophosphamide after Bone Marrow Transplantation Is Not Associated with an Increased Risk of Donor-Derived Malignancy

Majzner

Mogri

Varadhan

et al. 2017

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

show abstract

“…[14][15][16] DCL represents a relatively rare complication that affects 0.1% of those who undergo transplantion. 17,18 In addition, it has been shown that five of six recipients with unexplained cytopenias received allografts from donors with DNMT3A mutation. 19 Nonmalignant outcome consequences of donor CHIP, such as graft function and/or immunologic impairment, may be more common than DCL and may thereby contribute to HSCT outcome.…”

Section: Introductionmentioning

confidence: 99%

Role of Donor Clonal Hematopoiesis in Allogeneic Hematopoietic Stem-Cell Transplantation

Frick

Chan

Arends

et al. 2019

JCO

184

139

View full text Add to dashboard Cite

Purpose Clonal hematopoiesis of indeterminate potential (CHIP) occurs in the blood of approximately 20% of older persons. CHIP is linked to an increased risk of hematologic malignancies and of all-cause mortality; thus, the eligibility of stem-cell donors with CHIP is questionable. We comprehensively investigated how donor CHIP affects outcome of allogeneic hematopoietic stem-cell transplantation (HSCT). Methods We collected blood samples from 500 healthy, related HSCT donors (age ≥ 55 years) at the time of stem-cell donation for targeted sequencing with a 66-gene panel. The effect of donor CHIP was assessed on recipient outcomes, including graft-versus-host disease (GVHD), cumulative incidence of relapse/progression (CIR/P), and overall survival (OS). Results A total of 92 clonal mutations with a median variant allele frequency of 5.9% were identified in 80 (16.0%) of 500 donors. CHIP prevalence was higher in donors related to patients with myeloid compared with lymphoid malignancies (19.2% v 6.3%; P ≤ .001). In recipients allografted with donor CHIP, we found a high cumulative incidence of chronic GVHD (cGVHD; hazard ratio [HR], 1.73; 95% CI, 1.21 to 2.49; P = .003) and lower CIR/P (univariate: HR, 0.62; 95% CI, 0.40 to 0.97; P = .027; multivariate: HR, 0.63; 95% CI, 0.41 to 0.98; P = .042) but no effect on nonrelapse mortality. Serial quantification of 25 mutations showed engraftment of 24 of 25 clones and disproportionate expansion in half of them. Donor-cell leukemia was observed in two recipients. OS was not affected by donor CHIP status (HR, 0.88; 95% CI, 0.65 to 1.321; P = .434). Conclusion Allogeneic HSCT from donors with CHIP seems safe and results in similar survival in the setting of older, related donors. Future studies in younger and unrelated donors are warranted to extend these results. Confirmatory studies and mechanistic experiments are warranted to challenge the hypothesis that donor CHIP might foster cGVHD development and reduce relapse/progression risk.

show abstract

“…Since the first case of DCHN was published by Fialkow et al in 1971 [3], several cases have been reported in the literature. Although the actual incidence of DCHN is unknown, it has been reported to be 1.2% by Boyd et al [4], .84% by the Tokyo Cord Blood Bank [5], .12% by the European Society for Blood and Marrow Transplantation [6], and .13% by the Japan Society for Hematopoietic Cell Transplantation [7].…”

Section: Introductionmentioning

confidence: 99%

Donor Cell–Derived Hematologic Neoplasms after Hematopoietic Stem Cell Transplantation: A Systematic Review

Suárez‐González

Martínez-Laperche

Kwon

et al. 2018

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

Development of de novo hematologic malignancies in donor cells after allogeneic stem cell transplantation (allo-SCT) provides a useful in vivo model to study the process of leukemogenesis. A systematic analysis of the cases reported in the literature was performed to identify risk factors and mechanisms involved in the pathogenesis of donor cell-derived hematologic neoplasms (DCHN) and leukemogenic transformation. Relevant data were extracted from 137 cases. Cases of DCHN show a wide heterogeneity with regard to recipient/donor age, sex mismatch, and conditioning regimen. Some characteristics, such as the type of primary disease, the type of hematologic malignancy of the DCHN, and the stem cell source used in the transplant procedure, differ from those expected. Mechanisms involved in the pathogenesis of DCHN are complex, and several hypotheses have been proposed, such as pre-existing hematologic neoplasms or premalignant clones in the donor, decreased immune surveillance, and damage to bone marrow microenvironment in the recipient. Most likely several if not all these mechanisms play a role in DCHN development. Novel approaches, such as next-generation sequencing to study consecutive samples after allo-SCT in these patients, appear to be promising to decipher the mechanisms of leukemogenesis.

show abstract

Donor cell-derived hematological malignancy: a survey by the Japan Society for Hematopoietic Cell Transplantation

Cited by 42 publications

References 16 publications

Post-Transplantation Cyclophosphamide after Bone Marrow Transplantation Is Not Associated with an Increased Risk of Donor-Derived Malignancy

Post-Transplantation Cyclophosphamide after Bone Marrow Transplantation Is Not Associated with an Increased Risk of Donor-Derived Malignancy

Role of Donor Clonal Hematopoiesis in Allogeneic Hematopoietic Stem-Cell Transplantation

Donor Cell–Derived Hematologic Neoplasms after Hematopoietic Stem Cell Transplantation: A Systematic Review

Contact Info

Product

Resources

About