Therapy-related, donor-derived AML responding to a second allogeneic BMT

Jacobs, Joannes F M; Brons, Paul; Simons, Annet; Reijden, Bert A. van der; Hoogerbrugge, Peter M.

doi:10.1038/sj.bmt.1705750

Cited by 10 publications

(6 citation statements)

References 7 publications

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“…This speaks to the importance of the two-hit hypothesis, in which a second insult to the marrow is required to develop frank malignancy. This could come from residual effects of chemotherapy 19, 47 , impaired immune surveillance 19 , or even elements in the marrow stroma and microenvironment that drive leukemogenesis 30 . Additionally, the authors suggest that telomere shortening related to stress hematopoiesis at the time of graft infusion could lead to genetic instability in engrafted cells 48, 49 and the development of frank malignancy 28 .…”

Section: Discussionmentioning

confidence: 99%

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

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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.

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Section: Discussionmentioning

confidence: 99%

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

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“…Another theory suggests that the residual effects of conditioning chemotherapy may damage the graft and cause a therapy related neoplasm as is classically associated with topoisomerase II inhibitors and alkylating agents. In a review by Wiseman, 96% of the patient with DCL had been exposed to either of these two classes of chemotherapeutics during conditioning and 47% had cytogenetic abnormalities consistent with t-AML including −7 and MLL gene rearrangements [ 6 , 10 , 11 ].…”

Section: Discussionmentioning

confidence: 99%

Donor Cell Myeloid Sarcoma in an Umbilical Cord Transplant Patient: A Case Report and a Review of the Literature

Hayes

Petersen

Malone

2015

Case Reports in Hematology

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Donor cell leukemia (DCL) represents a rare complication of allogeneic transplantation. The precise incidence remains unclear, though it may be higher following umbilical cord blood transplants. Here, we present an unusual case of a patient with B-ALL who presented with a donor derived myeloid sarcoma of the heart following a double cord blood transplant. To our knowledge, it is the first case of sarcomatous or chloromatous presentation of DCL following a UCBT.

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“…Leukaemia recurred 62 days after marrow transplantation with blasts showing a male genotype. Since then, several cases reports of DCL have been reported [2][3][4][5][6][7][8][9][10][11] and also some small case series [12][13][14][15]. Increased reporting in the last decade likely reflects the increasing number of HCT performed but also improved ability to identify donor cell origin.…”

Section: Introductionmentioning

confidence: 99%

European experience and risk factor analysis of donor cell-derived leukaemias/MDS following haematopoietic cell transplantation

et al. 2018

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Donor cell leukaemia (DCL) is a rare complication of allogeneic haematopoietic cell transplantation (HCT). We have investigated the prevalence and outcome of donor cell haematology malignancies within centres registered with the European Society of Blood and Marrow transplantation (EBMT). We have sought to identify risk factors to shed light on the pathogenesis of DCL as a model for leukaemogenesis. DCL cases were identified by questionnaire and a follow-up questionnaire requested detailed data. Control subjects from the EBMT registry who had not developed DCL were used for a matched pair analysis to identify risk factors. We identified 38 patients with DCL; the estimated prevalence was 80.5/100,000 transplants. Patients were predominantly treated for haematological malignancy. A clone was retrospectively identified in 7/25 (28%) donors for whom data was available. Overall survival was poor with 29/38 patients dead a median of 11 (range 0-91) months after DCL diagnosis. Matched case-pair analysis identified three factors on multivariate analysis as significantly associated with an increased risk for DCL: use of growth factors within the first 100 days after transplantation, in vivo T-cell depletion and multiple allografts. The risk factors identified, support reduced immune surveillance and replicative stress as pathogenic in the development of DCL.

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Therapy-related, donor-derived AML responding to a second allogeneic BMT

Cited by 10 publications

References 7 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

Donor Cell Myeloid Sarcoma in an Umbilical Cord Transplant Patient: A Case Report and a Review of the Literature

European experience and risk factor analysis of donor cell-derived leukaemias/MDS following haematopoietic cell transplantation

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