The non‐relapse mortality rate for patients with diffuse large B‐cell lymphoma is greater than relapse mortality 8 years after autologous stem cell transplantation and is significantly higher than mortality rates of population controls

Abstract

SummaryHigh dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the preferred treatment modality for patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL). To assess long‐term outcomes of these patients, we retrospectively analysed data from 309 consecutive patients who underwent ASCT for DLBCL between 1994 and 2006. We found that non‐relapse mortality (NRM) became the major cause of death beginning approximately 8 years after ASCT. The most common causes of NRM during the study period were respiratory failure (31%), infection (13%), cardiac toxicity (15%) and secondary malignancy (15%). The strongest predictor of relapse mortality (RM) was disease status at transplant: patients who were in second or greater complete or partial remission had a higher risk of RM than those in first complete or partial remission [hazard ratio (HR) 3·7, P < 0·001], as did those who were relapsed or refractory (HR 4·9, P < 0·001). We describe the longest reported follow‐up of a large cohort of DLBCL patients uniformly‐treated with ASCT. Although relapse was initially the more likely cause of death, NRM exceeded RM after 8 years. After ASCT, surviving patients have significantly increased risk mortality rates relative to the general population and this excess risk persists over time.

Conditional survival and cause-specific mortality after autologous hematopoietic cell transplantation for hematological malignancies

“…15 In the current study, SMNs were the most common cause of non-relapse mortality among aHCT recipients, accounting for 9% of all deaths, and placing the cohort at a 3.9-fold increased risk of cancer-related death; these findings are similar to previous studies. 3, 16–18 HL patients, were at a 14.8-fold increased risk of SMN-related death compared to the general population. Previous studies have demonstrated that the risk of developing therapy-related leukemia is significantly elevated among patients with HL and NHL treated with aHCT, and carries a dismal prognosis.…”

Long‐term outcomes among 2‐year survivors of autologous hematopoietic cell transplantation for Hodgkin and diffuse large b‐cell lymphoma

“…With a median follow‐up of 7.6 years and with 68% having received total body irradiation (TBI)–based preparative regimens, the cohort had a 13‐fold increased risk of late death in comparison with the general population. Subsequent reports have confirmed an increased risk of late mortality . In addition, mostly single‐center studies have reported high rates of organ impairment, functional limitations, and subsequent malignant neoplasms (SMNs) in auto‐HCT survivors …”

“…Subsequent reports have confirmed an increased risk of late mortality. [10][11][12][13] In addition, mostly single-center studies have reported high rates of organ impairment, functional limitations, and subsequent malignant neoplasms (SMNs) in auto-HCT survivors. [13][14][15] To address the gaps in the literature, we selected a representative, multicenter cohort of 2-year disease-free survivors of auto-HCT for cHL or DLBCL who were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR).…”

The Muddied Waters of Ibrutinib Therapy

“…Although patients usually have immune reconstitution after this transplantation procedure, T and B cell function can be impaired for a prolonged period. Follow-up of these patients has shown them to be at increased risk for non-relapse mortality, with up to 13% dying due to an infectious disease during long-term follow-up [8]. …”

“…This immunodeficiency is due to BTK mutations that result in deficient BTK function. These children often suffer from opportunistic infections during early life [8]. …”