Secondary Malignancy after Allogeneic Stem Cell Transplantation: Incidence and Risk Factors.
Authors: Hosing Chitra , Saliba Rima M. , De Lima Marcos , Giralt Sergio , Ghosh Shubhra , Hsu Yvonne , Anderlini Paolo , Hymes Sharon R. , Andersson Borje , Khouri Issa F. , Champlin Richard , Couriel Daniel 
Published: April 2020

Abstract
Survivors of allogeneic hematopoietic stem cell transplantation may be at increased risk for developing secondary malignancies. We evaluated 815 adult patients who underwent allogeneic HSCT at our institution between 1/98 and 9/02. Data was collected from the Blood and Marrow Transplant database of the University of Texas M.D. Anderson Cancer Center.
RESULTS: Patient characteristics are given in Table 1.
Table 1. Patient Characteristics N (%) Age Median (range) 47 (18–75) Sex F/M 333 (41)/482 (59) Diagnosis Myeloid malignancy 429 (53) Lymphoid malignancy 308 (38) Multiple Myeloma 31 (4) Other 47 (6) Race Caucasian 645 (79) African- American 34 (4) Other 135 (17) Preparative Regimen Myeloablative (TBI/no TBI) 434 (53) {102 (24)/332 (76)} Non-Myeloablative 381 (47) Prior Autologous Transplant 78 (10) Graft versus Host Disease Acute grade I-IV/Chronic (extensive and limited) 381 (47)/389 (48)
After a median follow up time in all survivors of 35 months (range, 1.3–74) from transplantation, a total of 34 patients (4%) developed a second malignancy (an additional 8 patients developed limited basal cell carcinoma of the skin). Median time to diagnosis of second malignancy was 11 months (range, 1–69 months) after transplantation. The most common non-hematologic malignancy was squamous cell carcinoma of the skin and oral cavity (10 patients), followed by lymphoma/post transplant lymphoproliferative disorder (5 patients), and melanoma (4 patients).
Table 2: Second Malignancy N (%) Squamous cell carcinoma 10 (29) Lymphoma or PTLD 5 (15) Myelodysplasia/Acute myelogenous leukemia 4 (12) Melanoma 4 (12) Colon Cancer 3 (9) Breast Cancer 3 (9) Lung Cancer 2 (6) Other 3 (9) Renal Cell Carcinoma 1 (3) Adenocarcinoma unknown origin 1 (3) Meningioma 1 (3)
The cumulative incidence for developing a secondary malignancy was 5.4% (SE ± 1%) at 5 years. On univariate analysis the rate of developing a second malignancy was higher in patients who were older than 45 years at the time of their transplant (HR 2.3, 95% CI 1.1–5.1, P value 0.03), African Americans (HR 3.2, 95% CI 1.1–9.4, P value 0.02) and males (HR 2.2, 95% CI 0.99–4.89, P value 0.05). These factors remained significant in a multivariate model. Additional factors that were evaluated but were not statistically significant were primary malignancy, preparative regimen (reduced intensity vs. myeloablative, TBI vs. non-TBI), source of stem cells, acute or chronic GVHD (as a time dependent variable), number of prior chemotherapy regimens, and history of prior autologous transplantation. At the time of last follow up 15 of 34 patients had died; in 8 patients the primary cause of death was the secondary malignancy.
CONCLUSIONS: The risk of developing a secondary malignancy was higher in patients who were older than 45 years of age at the time of transplantation, African-Americans and males. Contrary to other reports having received TBI in the preparative regimen or GVHD did not increase this risk. This may be due to the relatively short median follow up time in this study, since secondary malignancies due to radiation may not peak in incidence till later. The most common second malignancy was squamous cell carcinoma of the skin and oral cavity. Survivors of allogeneic transplantation should be monitored carefully for the development of secondary malignancy and at the minimum should get an annual full skin examination.