Abstract
Introduction
Elderly patients (≥60 years of age) with acute lymphoblastic leukemia/lymphoma (ALL) have a poor prognosis compared to younger adults. This is thought to be due to comorbidities, treatment-related mortality, adverse disease biology, low rates of complete remission (CR), high risk of relapse, and ineligibility for allogeneic hematopoietic stem cell transplantation (HSCT). Since it is unclear how all these factors play into the poor prognosis of elderly ALL, we sought to describe the presentation, treatment outcomes, and predictors of survival at our multi-site institution.
Methods
After IRB approval, we performed a retrospective study of patients (pts) ≥60 years old diagnosed with ALL from 2000-2017 at Mayo Clinic Rochester, Arizona, and Florida. Statistical analysis was performed using JMP 10.0 software.
Results
Baseline characteristics
We identified 124 consecutive pts with elderly ALL. The median age at time of diagnosis was 67 (60-86) and 74 (60%) were male. Median time of follow-up was 15.6 months (range 0.2-132). 77 (62%) were deceased at the time of last follow-up: 37 deaths related to disease, 24 due to infection or other causes, and 16 unknown.
At time of diagnosis, 108 (87%) pts had B-cell ALL, of which 40 (37%) were Philadelphia chromosome positive (Ph+). Only 16 (13%) pts had T-cell ALL. Overall, 24 (19%) had an ECOG performance status (PS) ≥2, and 22 (18%) had a Charlson Comorbidity Index (CCI) ≥3. Further baseline characteristics including cytogenetics and FISH studies are detailed in Table 1.
Treatment and Outcomes
102/124 (82%) elected to undergo induction. Of these, 19 (19%) had an up-front dose reduction. The most common induction regimen was Hyper-CVAD, which was used in 62 (61%), concomitantly with rituximab in 21, and tyrosine kinase inhibitors (TKIs) in 17. Asparaginase-based chemotherapy was used in 27 (26%) pts. The remaining 13 (13%) received other regimens. Complete remission (CR/CRi) was achieved in 92 (90%) pts. 11 (11%) had primary refractory disease, of which 7 were refractory to multiple lines of therapy. Median time to CR was 30 days (range 10-352), requiring a median of 1 cycle (range 1-8) of chemotherapy. 5 (5%) died within 60 days of starting treatment, and by Day 100 there were a total of 10 (10%) deaths; these were related to subdural hematoma (3), infection (2), treatment discontinuation (1), and unknown causes (4).
Palliative therapy up-front was chosen in 22/124 (18%), which included chemotherapy (e.g. vincristine and steroids), TKIs or hospice. 7 (32%) of these pts achieved CR within a median time of 54 days (range 23-128). The median overall survival (mOS) in the palliative group was 5.7 months (interquartile range [IQR] 1.7-12.1).
Relapse occurred in 42 (42%) pts within a median time of 9.9 months (range 0-71.5); 10 (24%) of these pts had an extramedullary relapse, including 3 with CNS leukemia. 31 (74%) were treated with salvage chemotherapy, while 10 (21%) chose palliative care. Median survival from the time of relapse was 5.7 months (IQR 2-18).
Overall, 34 (27%) underwent HSCT: allogeneic HSCT in 33, and autologous HSCT in 1. Of these, 29 (85%) were in CR1, and 5 (15%) were in CR2. The median age at time of HSCT was 65 (range 60-73). 3 (9%) died within 100 days of HSCT, due to early relapse (2; both were in CR1) and acute graft-versus-host disease (1). 11 (31%) relapsed after HSCT, within a median time of 9 months (range 1-30). Median survival after HSCT was 27.4 months (IQR 0.7-not reached [NR]).
Predictors of Survival
Elderly ALL across the three Mayo Clinic campuses had a mOS of 20.8 months (IQR 9.4-87.3), which was inferior compared to our adult ALL (age 18-59) cohort in Rochester, who had a mOS of 51.1 months (IQR 15.3-NR) (Figure 1). In univariate analysis, which included the presenting variables shown in Table 1, only age, ECOG PS, CCI, and LDH negatively influenced survival (P <0.05). These factors continued to significantly predict for poor survival in multivariate analysis (Table 2).
Conclusions
ALL has worse outcomes in elderly pts compared to younger adults. However, treatment-related mortality was relatively low in our cohort even though the majority of pts underwent induction. Interestingly, we found that survival was influenced by age, ECOG PS, CCI, and LDH at time of diagnosis, rather than by cytogenetics or other biological features. Our data needs to be verified in a larger cohort. Nevertheless, this could be the first step toward a prognostic model in elderly ALL.
No relevant conflicts of interest to declare.
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