Second Malignancies after Stem Cell Transplantation. Single Center Report
Authors: Oliver Ana Carolina , Irigoin Victoria , Isern Melanie , Figueroa Byron , Perdomo Martina , Urrutia Romina , Galeano Sebastian , Riva Eloisa , Pierri Silvia , Bello Laura , Marcalain Virginia , Gai Regis , Muxi Pablo 
Published: December 2024

Introduction: Stem cell transplantation (SCT), both autologous and allogeneic has significantly improved overall survival mainly in patients with hematologic malignancies. However, the use of high dose chemotherapy carries an increased risk of second malignancies (SM).

Objectives: Analyze and describe the rate and type of second malignancies after SCT in patients transplanted at British Hospital between 1995-2022 as well as their outcomes.

Methods: Observational retrospective study of a consecutive cohort of adult patients transplanted in our center in the period described above. Non-melanoma localized skin cancer was excluded. Second malignancies were documented in those patients alive at the time of last contact or from medical records in available cases.

Results: 657 patients were transplanted in our unit in this period. Median age at SCT was 54 years (18-75). 580 (88,3%) were autologous SCT, 77 (11,7%) allogeneic SCT.

Multiple Myeloma (MM) accounted for 37,6% % (247 patients) Non-Hodgkin Lymphoma (NHL) 233 (35%) Hodgkin Lymphoma 71 (10,8%) Acute Myeloid Leukemia (AML) 52 (7,9%) Acute Lymphoblastic Leukemia (ALL) 14 (2,1%) Myelodysplastic Syndrome (MDS) 12 (1,8%) other 28 (4,2%) The most frequent conditioning regimens were high dose Melphalan and BEAM for autologous SCT, BuCy for allogeneic SCT.

The incidence of second malignancies was 8,7% (57 cases); 25 (43,8%) were hematologic malignancies and 32 (56,2%) solid tumors. Only 1 patient (1,3%) of patients who received allogeneic SCT developed a SM, vs 56 (9,7%) of those who received autologous SCT p=0,003

Neoplastic disorders prior to SCT were documented in 33 patients (5%), however none of these patients developed SM after SCT.

Median follow up for the entire cohort was 45 months (0-311), for allogeneic SCT median follow up was 20 months (0,1-289) and for autologous SCT 47 months (0-311)

Median time from SCT to second malignancy diagnosis was 55 months (2,5-241).Mean time 54 months for hematological malignancies and 79 months for solid tumors (p=0,009)

Among patients transplanted for MM, 20 (8%) developed a SM, 70% solid tumors, among those transplanted for lymphomas, 36 (11,8 %) developed a SM, mainly hematological (53%)

41% patients who developed a second malignancy received a single line of chemotherapy prior to SCT, 37% 2 lines and 22 % 3 or more lines. Alkylating agents were used in 47 (87%) Topoisomerase inhibitors in26 (49%) Previous or post SCT radiotherapy (RT) 11 (19%)

Overall survival (OS) in the entire population was 86 months (IC:69-103) for MM patients OS at 5 and 10 years was 37% and 34%, for patients with Lymphoma OS at 5 and 10 y was 50% and 44% (p=0,0001)

5 and 10 year OS for allogeneic transplanted patients was 31% and for autologous SCT was 43% and 38%

OS for patients with MM was not influenced by the development of a second malignancy, 68 months (56-79) vs 75 months (18-132) p=0,391 for patients with or without a SM respectively and showed a tendency for a shorter OS in patients with Lymphoma who developed SM 8,4 years vs 14,9 years p=0,182

Conclusion: This is the first study to analyze the rate and characteristics of second malignancies among transplanted patients in our country and region. Our center provides care for patients both belonging to public and private system. It sheds light on this complication and can lead to a preventive individualized approach. Patients transplanted for MM show an increased incidence of solid tumors in contrast to myeloid malignancies in those transplanted for lymphomas. Median follow up for patients who received allo-SCT was significantly shorter than that of autologous SCT transplanted patients which may explain the lower incidence of documented SM in that population. Moreover patients allografted are younger and have usually an earlier mortality rate than patients who receive autologous SCT and this could be also an explanation for our findings.