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Effect of autologous hematopoietic stem cell transplant on the development of second primary malignancies in multiple myeloma patients.

ABSTRACT: Autologous stem cell transplant (aHSCT) is associated with improved survival for multiple myeloma (MM) patients but may be associated with second primary malignancy (SPM) development. Using the California Cancer Registry linked to statewide hospitalization data, we determined the cumulative incidence (CMI) of SPMs more than 1 year after MM diagnosis, accounting for the competing risk of death. AHSCT recipients were matched 1:2 to non-aHSCT patients. Adjusted hazard ratios (aHR) were estimated using the Fine and Gray method. Among 16,331 patients, 933 (5.7%) developed a SPM more than 1 year after diagnosis. The 10-year CMI of developing any SPM was 6.6%, 5.7% for solid tumor SPM and 0.9% for hematologic malignancies. The 10-year CMI of developing any SPM was similar among aHSCT [9.1% (7.7-10.7%)] and non-aHSCT [7.5% (6.5-8.6%)] (P?=?0.26) recipients and there was no difference in solid-tumor SPMs (P?=?0.98). The 10-year CMI of hematologic SPMs was higher among aHSCT recipients [2.1% (1.4-2.9%) vs. 0.8% (0.5-1.2%); P?=?0.005], corresponding to a 1.3% absolute increase and an aHR of 1.51 (1.01-2.27). Ten-year myeloma-specific and non-cancer mortality rates were 59% (58.2-60.0%) and 18.1% (17.4-18.8%), respectively. Although aHSCT was associated with a small increase in hematologic SPMs, mortality was driven by MM and non-cancer causes.

SUBMITTER: Rosenberg AS

PROVIDER: S-EPMC7791054 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Effect of autologous hematopoietic stem cell transplant on the development of second primary malignancies in multiple myeloma patients.

Rosenberg A S AS Brunson A A Tuscano J J Jonas B A BA Hoeg R R Wun T T Keegan T H M THM

Blood cancer journal 20210107 1

Autologous stem cell transplant (aHSCT) is associated with improved survival for multiple myeloma (MM) patients but may be associated with second primary malignancy (SPM) development. Using the California Cancer Registry linked to statewide hospitalization data, we determined the cumulative incidence (CMI) of SPMs more than 1 year after MM diagnosis, accounting for the competing risk of death. AHSCT recipients were matched 1:2 to non-aHSCT patients. Adjusted hazard ratios (aHR) were estimated us ...[more]

PMID: 33414400

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Project description:Autologous hematopoietic stem cell transplantation (ASCT) is a standard treatment for multiple myeloma (MM). Consensus guidelines recommend collecting sufficient stem cells in case there is a need for stem cell boost for delayed/poor engraftment or for future second ASCT. However, collecting and storing backup stem cells in all patients requires significant resources and cost, and the rates of backup stem cell utilization are not well studied. We sought to examine the utilization of backup stem cells (BSCs) in patients with MM undergoing ASCT. Patients with MM aged ≥18 years old who underwent first ASCT at our institution from January 2010 through December 2015 and collected sufficient stem cells for at least 2 transplants were included in this single-center retrospective study. This timeframe was selected to allow for adequate follow-up. A total of 393 patients were included. The median age was 58 years (range, 25-73). After a median follow-up of 6 years, the median progression-free survival (PFS) of the cohort was 3 years. Sixty-one percent (n = 240) of patients progressed or relapsed. Chemotherapy-based mobilization was used in almost all patients (98%). The median total CD34+ cells collected was 18.2 × 106/kg (range, 3.4-112.4). A median of 5.7 × 106 CD34+ cells/kg (range, 1.8-41.9) was infused during the first ASCT, and a median of 10.1 × 106 CD34+ cells/kg (range, 1.5-104.5) was cryopreserved for future use. Of the patients, 6.9% (n = 27) used backup stem cells, with 2.3% (n = 10) using them for stem cell boost, 4.6% (n = 18) for a second salvage ASCT, including 1 patient for both stem cell boost and second ASCT. Rates of backup stem cell use among patients aged <60, 60-69, and ≥70 years were 7.8%, 5.7%, and 5.9%, respectively. There was a trend toward higher rates of backup stem cell use for second ASCT in patients who were younger, had suboptimal disease control at time of first ASCT, and longer PFS. The median dose of stem cell boost given was 5.6 × 106 CD34+ cells/kg (range, 1.9-20). The median time from stem cell boost to neutrophil, hemoglobin, and platelet engraftment was 4 (range, 2-11), 15 (range, 4-34), and 12 (range, 0-34) days, respectively. Lower CD34+ dose and older age at time of ASCT predicted need for stem cell boost. With new salvage therapies for relapsed MM, the rates of second ASCT are very low. The low rates of use suggest that institutional policies regarding universal BSC collection and long-term storage should be reassessed and individualized. However, need for stem cell boost in 2.3% of patients may present a challenge to that.

Project description:Autologous hematopoietic stem cell transplantation (AHCT) improves survival in patients with multiple myeloma (MM) but is associated with morbidity and nonrelapse mortality (NRM). Hematopoietic cell transplant comorbidity index (HCT-CI) was shown to predict risk of NRM and survival after allogeneic transplantation. We tested the utility of HCT-CI as a predictor of NRM and survival in patients with MM undergoing AHCT. We analyzed outcomes of 1156 patients of AHCT after high-dose melphalan reported to the Center for International Blood and Marrow Transplant Research. Individual comorbidities were prospectively collected at the time of AHCT. The impact of HCT-CI and other potential prognostic factors, including Karnofsky performance score (KPS), on NRM and survival were studied in multivariate Cox regression models. HCT-CI score was 0, 1, 2, 3, and >3 in 42%, 18%, 13%, 13%, and 14% of the study cohort, respectively. Subjects were stratified into 3 risk groups: HCT-CI score of 0 (42%) versus HCT-CI score of 1 to 2 (32%) versus HCT-CI score > 2 (26%). Higher HCT-CI was associated with lower KPS < 90 (33% of subjects score of 0 versus 50% in HCT-CI score > 2). HCT-CI score > 2 was associated with melphalan dose reduction (22% versus 10% in score 0 cohort). One-year NRM was low at 2% (95% confidence interval, 1% to 4%) and did not correlate with HCT-CI score (P = .9). On multivariate analysis, overall survival was inferior in groups with HCT-CI score of 1 to 2 (relative risk, 1.37, [95% confidence interval, 1.01 to 1.87], P = .04) and HCT-CI score > 2 (relative risk, 1.5 [95% confidence interval, 1.09 to 2.08], P = .01). Overall survival was also inferior with KPS < 90 (P < .001), IgA subtype (P ≤ .001), those receiving >1 pretransplant induction regimen (P = .007), and those with resistant disease at the time of AHCT (P < .001). AHCT for MM is associated with low NRM, and death is predominantly related to disease progression. Although a higher HCT-CI score did not predict NRM, it was associated with inferior survival.

Dataset Information

Effect of autologous hematopoietic stem cell transplant on the development of second primary malignancies in multiple myeloma patients.

Publications

Effect of autologous hematopoietic stem cell transplant on the development of second primary malignancies in multiple myeloma patients.

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