Increased incidence of malignant tumors in dogs after total body irradiation and marrow transplantation

Deeg, H. Joachim; Prentice, Ross L.; Fritz, T.E.; Sale, George E.; Lombard, Louise S.; Ed, Thomas; Storb, Rainer

doi:10.1016/0360-3016(83)90325-5

Cited by 41 publications

(15 citation statements)

References 21 publications

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“…2 Moreover, at the time, Cy seemed a better choice than regimens based on total body irradiation since it promised a lesser early procedure-related risk of marrow ablation as well as lack of infertility, growth retardation, cataract formation and carcinogenicity in the future. 33,34 Adding ATG to the protocol may explain, at least partially, consistent engraftment in 14/15 patients and the low incidence of severe acute GVHD in our patients. In vivo depletion of residual T cells of the recipient may facilitate engraftment, whereas due to anticipated 2-3 weeks half-life time of ATG circulating in vivo may explain relatively low incidence of severe GVHD, due to partial depletion of donor T cells in vivo through antibody-dependent cellmediated cytotoxicity.…”

Section: Discussionmentioning

confidence: 73%

Nonmyeloablative stem cell transplantation using lymphoablative rather than myeloablative conditioning in the prefludarabine era by ATG and limiting doses of cyclophosphamide

Bitan

Shapira

et al. 2005

Bone Marrow Transplant

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Section: Discussionmentioning

confidence: 73%

Nonmyeloablative stem cell transplantation using lymphoablative rather than myeloablative conditioning in the prefludarabine era by ATG and limiting doses of cyclophosphamide

Bitan

Shapira

et al. 2005

Bone Marrow Transplant

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“…Animal studies in dogs or monkeys given irradiation and hematopoietic stem cell transplantation revealed a striking increase in the development of solid tumors compared to controls [6,7]. In general, the risk of developing secondary neoplasms after BMT and TBI increased with time.…”

Section: Discussionmentioning

confidence: 97%

Breast Cancer in a Male Patient after Treatment of Acute Lymphoblastic Leukemia Including Total Body Irradiation and Bone Marrow Transplantation

et al. 2004

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Background: With increasing numbers of patients subjected to total body irradiation and bone marrow transplantation for treatment of several systemic malignancies more and more patients with second malignancies were observed. Case Report: We report the case of a 29- year-old man who developed breast cancer 13 years after treatment for acute lymphoblastic leukemia. Therapy for leukemia included total body irradiation (TBI) and bone marrow transplantation (BMT). Breast cancer was treated with mastectomy and irradiation of the left chest wall. 17 months later the patient developed malignant pleural effusion and died despite chemotherapy and hormonal therapy due to further tumor progression. Conclusion: The increased risk for secondary solid cancers after TBI and BMT and the greater risk among younger patients indicate the need for lifelong careful follow up.

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“…3 Consistent with this observation, an increased incidence of cancer was previously observed in dogs given TBI before transplant (no relationship with increasing dosage was indicated) compared to dogs not receiving TBI. 8 Azathioprine (AZA) and CsA have been reported to be associated with an increased risk for secondary neoplasms in solid organ transplant recipients 7 and, also, AZA appears to promote/facilitate secondary neoplasms when used as treatment for chronic GVHD. 9 In contrast to AZA, CsA is not mutagenic but rather impairs functional T cell-mediated tumor surveillance.…”

Section: Discussionmentioning

confidence: 99%

Anaplastic squamous cell carcinoma (SCC) in a patient with chronic cutaneous graft-versus-host disease (GVHD)

Gmeinhart

Hinterberger

Greinix

et al. 1999

Bone Marrow Transplant

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Summary:We describe an allogeneic bone marrow (BM) recipient who developed aggressive, metastasizing squamous cell cancer (SCC) of the skin, and discuss possible risk factors in the development of this secondary solid tumor. The patient had been treated with cyclosporine (CsA), methyl-prednisolone and thalidomide for 3 years because of extensive de novo chronic cutaneous GVHD occurring 1 year after BMT. Ten years after BMT a locally invasive and metastasizing SCC occurred on the patient's neck, and diagnosis was confirmed by H&E histopathology and cytokeratin-immunohistochemistry. Analysis of genomic DNA did not reveal p53 mutations nor were HPV sequences detectable. Risk factors included conditioning for BMT with total body irradiation (TBI) and cyclophosphamide (Cy), immunosuppressive treatment for GVHD, and extensive exposure to UV radiation before and after BMT. Despite surgery and adjuvant chemotherapy with 5-fluorouracil (5-FU) the patient died 1 year after the diagnosis of SCC. Keywords: secondary malignancy; squamous cell carcinoma; GVHD; immunosuppression With numbers of BM transplants from related and unrelated donors increasing recently the frequency of secondary neoplasms which impair long-term outcome and survival of the BM recipients has also been increasing. The risk of developing secondary cancer after allogeneic BMT has been reported to be increased 6.69-to 11-fold over that of an age-matched population. 1,2 Whereas lymphoproliferative cancers, myelodysplastic syndrome, acute leukemia and non-Hodgkin's lymphoma predominate in the first years after BMT, solid cancers including neoplasms of the central nervous system, bone, inner organs, skin and mucosal sur- faces occur progressively 10-15 years thereafter. 1-3 The largest cohort study on nearly 20 000 allogeneic BM recipients showed the cumulative incidence for secondary solid tumors to be 6.7%. Case reportSCC was diagnosed in a previously healthy 26-year-old Caucasian male patient in January 1985 who subsequently received 8 units of packed red blood cells and 4 units of platelets. Five months later, after conditioning with 200 mg Cy/kg body weight (b.w.) over 4 days and TBI of 3 Gy, he received 2.7 ϫ 10 8 nucleated cells (NC)/kg b.w. from his HLA class I and II identical brother. Methotrexate (MTX) according to the Seattle protocol was used as GVHD prophylaxis. Neutrophil counts of more than 0.5 ϫ 10 9 /l and 1 ϫ 10 9 /l were reached on days ϩ35 and ϩ53, respectively, after BMT. Unsupported platelets Ͼ20 ϫ 10 9 /l, hematocrit Ͼ30% and reticulocytes Ͼ20 000/ml without the need for further transfusion were reached on days ϩ24 and ϩ12, respectively. Donor cell engraftment was documented by the presence of donor ABO blood group. Because of poor marrow function MTX was stopped on day ϩ39. The patient showed no signs of acute GVHD and was discharged on day ϩ49 post BMT.One year after BMT, he developed de novo onset chronic cutaneous GVHD with lichenoid lesions on the lips and oral mucosa. We initiated systemic immunosuppression with 1.5 mg prednisolo...

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Increased incidence of malignant tumors in dogs after total body irradiation and marrow transplantation

Cited by 41 publications

References 21 publications

Nonmyeloablative stem cell transplantation using lymphoablative rather than myeloablative conditioning in the prefludarabine era by ATG and limiting doses of cyclophosphamide

Nonmyeloablative stem cell transplantation using lymphoablative rather than myeloablative conditioning in the prefludarabine era by ATG and limiting doses of cyclophosphamide

Breast Cancer in a Male Patient after Treatment of Acute Lymphoblastic Leukemia Including Total Body Irradiation and Bone Marrow Transplantation

Anaplastic squamous cell carcinoma (SCC) in a patient with chronic cutaneous graft-versus-host disease (GVHD)

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