Malignant Neoplasms in Long-Term Survivors of Bone Marrow Transplantation

Kolb, Hans‐Jochem; Socié, Gèrard; Duell, Thomas; Lint, M. T. Van; Thewis, André; Apperley, Jane F.; Nekolla, E.; Ljungman, Per; Jacobsen, N; Weel, M. Van; Wick, R. R.; Weiß, Melanie; Prentice, HG

doi:10.7326/0003-4819-131-10-199911160-00004

Cited by 244 publications

(116 citation statements)

References 24 publications

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“…As for conditioning regimen, radiation-containing regimen was not significantly associated with LM after HSCT in our series, although radiation was reported to be associated with LM after HSCT. [3][4][5] This is probably because of absolute low patient number who developed LM. Recently, Flu-based preconditioning regimen is widely used in HSCT for SAA from MSD or alternative donors.…”

Section: Discussionmentioning

confidence: 99%

“…Cumulative incidence of LM was 0.8% at 10 years and 2.5% at 20 years, respectively, which was much lower than those in previous reports. [3][4][5][6] As for conditioning regimen for SAA in patients with LM, four received radiation-containing regimen and one non-irradiation regimen. Comparisons of cumulative incidence of LM between radiation and non-radiation regimen did not reach statistical significance (2.5 vs 3.1% at 20 years, P ¼ 0.718).…”

Section: Resultsmentioning

confidence: 99%

“…3,4 In SAA, LM are also reported in the patients with HSCT and its occurrence is related to radiation-containing conditioning regimen and GVHD grade in adults, 5,6 however, the incidence and prognostic factors of LM in children with SAA who undergo HSCT are totally unknown.…”

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confidence: 99%

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Long-term outcome of childhood aplastic anemia patients who underwent allogeneic hematopoietic SCT from an HLA-matched sibling donor in Japan

Kikuchi

Yabe

Katô³

et al. 2012

Bone Marrow Transplant

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We report long-term outcomes of 329 childhood severe aplastic anemia (SAA) patients who underwent hematopoietic SCT (HSCT) from an HLA-matched sibling donor in the Japanese Hematopoietic Cell Transplantation Registry. OS and EFS at 10 years were as high as 89.7 þ / À 1.7% and 85.5 þ / À 2.0%, respectively. Five cases of late malignancies (LM) were identified (malignant peripheral nerve sheath tumor, thyroid carcinoma, colon carcinoma, MDS and hepatoblastoma). Cumulative incidence of LM was 0.8% at 10 years and 2.5% at 20 years, respectively, which was lower than that in previous reports. This low incidence is in keeping with the low occurrence of skin cancer in Japanese population and of acute GVHD in our study group. Radiation-containing conditioning was not significantly associated with the incidence of LM after HSCT probably because of absolute low patient number who developed LM in our series. In terms of LM development after HSCT, low-dose TBI in HSCT for SAA to avoid graft rejection, which is commonly used in Japan, might be tolerable in the Japanese population because of its low incidence. Keywords: aplastic anemia; childhood; hematopoietic SCT; long-term outcome; late malignancies INTRODUCTION Aplastic anemia is a hematopoietic disorder characterized by pancytopenia and BM hypoplasia. Therapeutic options for severe aplastic anemia (SAA) are immunosuppressive therapy and hematopoietic SCT (HSCT). In children, if an HLA-matched sibling donor (MSD) is available, HSCT is the first line of therapy for SAA. HSCT from MSD is an established standard therapy for SAA in children and high survival rates have already been reported. However, little is known about long-term outcomes of these children.Late malignancies (LM) are serious complications for patients who undergo HSCT. 3,4 In SAA, LM are also reported in the patients with HSCT and its occurrence is related to radiation-containing conditioning regimen and GVHD grade in adults, 5,6 however, the incidence and prognostic factors of LM in children with SAA who undergo HSCT are totally unknown.In this article, we report long-term outcomes of childhood SAA patients who underwent HSCT from MSD in the centers of the Japanese Hematopoietic Cell Transplantation Registry and describe the occurrence of LM.

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Section: Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Long-term outcome of childhood aplastic anemia patients who underwent allogeneic hematopoietic SCT from an HLA-matched sibling donor in Japan

Kikuchi

Yabe

Katô³

et al. 2012

Bone Marrow Transplant

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“…A study from EBMT of 1036 recipients surviving >5 years (median follow-up=10.7 years, range 5–22) did not find donor-recipient histocompatibility to be a significant risk factor for development of new malignancies. 129 Unpublished data from the Fred Hutchinson Cancer Research Center (FHCRC) found that the relative risk of SN in allogeneic HCT recipients, after adjustment for both aGVHD and cGVHD, was higher in those recipients who received peripheral blood stem cell (PBSC) grafts compared to bone marrow (RR=1.6, 95%CI=1.2–2.10, p=0.001). The fewer number of UCB transplants and their shorter follow-up precluded an accurate assessment of risk in UCB recipients.…”

Section: Disease- and Transplant-related Risk Factorsmentioning

confidence: 99%

“…180 Other virus-related cancers are rare, but observed elevations in risk for cervical cancer (HPV) and liver cancer (HCV, hepatitis B virus [HBV]) support the likely importance of oncogenic viruses in cancer risk after allogeneic HCT. 24,39,43,181 A single case reports suggests the possibility of donor T-cells acquiring human T-lymphotropic virus (HTLV1). 182 Polyomaviruses also represent an emerging group of viruses requiring study because of their potential to cause epithelial malignancy.…”

Section: Non-transplant-related Risk Factorsmentioning

confidence: 99%

National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Subsequent Neoplasms Working Group Report

Morton

Saber

Baker

et al. 2017

Biology of Blood and Marrow Transplantation

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Subsequent neoplasms (SN) following hematopoietic cell transplantation (HCT) cause significant patient morbidity and mortality. Risks for specific SN types vary substantially, with particularly elevated risks for post-transplant lymphoproliferative disorders, myelodysplastic syndrome/acute myeloid leukemia, and squamous cell malignancies. This consensus document provides an overview of the current state of knowledge regarding SN after HCT and recommends priorities and approaches to overcome challenges and gaps in understanding. Numerous factors have been suggested to impact risk, including patient-related (e.g., age), primary disease-related (e.g., disease type, pre-HCT therapies), and HCT-related characteristics (e.g., type and intensity of conditioning regimen, stem cell source, development of graft-versus-host disease). However, gaps in understanding remain for each of these risk factors, particularly for patients receiving HCT in the current era due to substantial advances in clinical transplantation practices. Additionally, the influence of non-transplant-related risk factors (e.g., germline genetic susceptibility, oncogenic viruses, lifestyle factors) is poorly understood. Clarification of the magnitude of SN risks and identification of etiologic factors will require large-scale, long-term, systematic follow-up of HCT survivors with detailed clinical data. Most investigations of the mechanisms of SN pathogenesis after HCT have focused on immune drivers. Expansion of our understanding in this area will require interdisciplinary laboratory collaborations utilizing measures of immune function and availability of archival tissue from SN diagnoses. Consensus-based recommendations for optimal preventative, screening, and therapeutic approaches have been developed for certain SN after HCT, whereas for other SN, general population guidelines are recommended. Further evidence is needed to specifically tailor preventative, screening, and therapeutic guidelines for SN after HCT, particularly for unique patient populations. Accomplishment of this broad research agenda will require increased investment in systematic data collection with engagement from patients, clinicians, and interdisciplinary scientists in order to reduce the burden of SN in the rapidly growing population of HCT survivors.

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Allogeneic Hematopoietic Stem Cell Transplantation

Tabbara¹,

Zimmerman²,

Morgan³

et al. 2002

Arch Intern Med

163

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Acute complications such as veno-occlusive disease of the liver, acute and chronic graft-vs-host disease (GVHD), and infectious conditions remain major obstacles for the success of allogeneic hematopoietic stem cell transplantation (HSCT). Progress in allogeneic HSCT depends on several factors, including the adequate prevention and management of associated complications, advances in the conventional management of diseases currently treated with allogeneic HSCT, expansion of the donor pool, selective control of GVHD, development of more effective preparative regimens to eradicate the neoplastic cell population, characterization of a new generation of hematopoietic growth factors and cytokines, and development of newer techniques for ex vivo manipulation of stem cells. Hematopoietic growth factor-mobilized donor progenitor cells collected from peripheral blood have been shown to be associated with rapid hematopoietic engraftment without an increase in the incidence of acute GVHD compared with allogeneic bone marrow transplantation. Implementation of this approach will enhance donor acceptance, eliminate the risk of general anesthesia, decrease cost, and reduce the risk of infectious complications by reducing the duration of neutropenia. Nonmyeloablative allogeneic stem cell transplantation represents a novel treatment approach that may lead to reduced toxic effects and extended use of this treatment in older patients and in those with malignant and nonmalignant disorders. However, GVHD and disease recurrence remain a challenge. Promising results have been reported in patients with refractory hematologic malignancies and in metastatic renal cell cancer. Because late complications are commonly encountered in patients receiving allogeneic HSCT, lifelong observation is needed.

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Malignant Neoplasms in Long-Term Survivors of Bone Marrow Transplantation

Abstract: The spectrum of neoplasms and immunosuppressive treatment with cyclosporine for chronic graft-versus-host disease as dominant risk factors indicate that immunosuppression is the major cause of malignant neoplasms in patients receiving marrow transplants.

Cited by 244 publications

References 24 publications

Long-term outcome of childhood aplastic anemia patients who underwent allogeneic hematopoietic SCT from an HLA-matched sibling donor in Japan

Long-term outcome of childhood aplastic anemia patients who underwent allogeneic hematopoietic SCT from an HLA-matched sibling donor in Japan

National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Subsequent Neoplasms Working Group Report

Allogeneic Hematopoietic Stem Cell Transplantation

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