Clinical Presentation, Risk Profiles and Outcomes of Chemotherapy without Bone Marrow Transplant in a Cohort of Minority Patients with Acute Lymphoblastic Leukemia from a Public Health Hospital
Authors: Ciobanu Bety , Sreenivasappa Shylendra B , Smiley Tracy , Yim Barbara , Kovarik Paula , Shah Mousami , Kouz Rafid , Ofori Samuel , Telfer Margaret Clare , Catchatourian Rosalind 
Published: April 2020

Background: Outcomes of therapy for adult population diagnosed with acute lymphoblastic leukemia (ALL) remain unsatisfactory. Chemotherapy with or without bone marrow transplant (BMT) is the mainstay of treatment. We sought to describe the outcomes of chemotherapy in our population of adults with ALL who were not eligible for bone marrow transplant due to socio-economic reasons.

Methods: Data from 50 patients (pts) with ALL over an 8-year period were studied as a retrospective cohort for clinical presentation, response, remission duration and long-term survival. Clinical and survival data were analyzed via Student’s T test and Fisher’s exact test. Time to relapse was analyzed with Kaplan-Meier life table analyses and Log Rank test.

Results: There were 16 (32%) women and 34 (68%) men diagnosed with ALL. Median age at diagnosis was 31 years. Hispanics were the majority group with 27 pts (54%), African Americans 11 (22%), Caucasians 8 (16%), and Asian 4 (8%). B precursor ALL was present in 39 pts (78%), T precursor ALL in 8 (16%), and Burkitt’s leukemia in 3 (6%). Cytogenetics were available in 42 pts (84%): 29 pts (58%) were intermediate risk, 12 (24%) poor risk, and 1(2%) good risk. Ph chromosome was present in 6 pts (12%). A WBC above 30,000/dL was seen in 13 pts (25.49%). Myeloid markers were present in 9 (17.64%), CD10 in 45 (88.23%), and CD34 in 34 (66.6%) pts. Four pts (7.84%) had CNS disease at presentation and 3 (5.9%) had mediastinal disease. Based on age, WBC count, cytogenetics, and CNS disease at diagnosis, there were 28 high-risk pts (56%) and 22 standard-risk pts (44%). Majority of pts 38 (76%) received a 4-drug induction chemotherapy (BFM protocol). Hyper-CVAD, and CALGB protocols were used in 6 pts each (12%).

A total of 42 pts (84%) achieved remission after first induction chemotherapy. There were 3 deaths (6%) and 5 (10%) nonresponders (NR). After the induction protocol, 19 pts remained in remission but 21 pts (50%) relapsed. Median time to first relapse (TTR) was 12 months. Relapsed pts were re-induced with 2nd line chemotherapy: Hyper-CVAD regimen in 10 pts (47.6%), BFM protocol in 4 (19%), and 33% with other regimens. Eleven pts (52.3%) entered a 2nd remission, 3 died, and 7 NR. Out of 11 pts who achieved a second remission, 5 pts later relapsed, 1 was still in remission at the last follow up, 2 underwent BMT and 3 were lost to follow up.

TTR was analyzed according to age, gender, ethnicity, immunophenotype, cytogenetics, WBC count, presence of CD10, CD34, myeloid markers and induction protocol and no significant differences were found.

Median overall survival was 16 months (range 1–97 months). Significant differences in survival were found with regards to cytogenetics (poor vs. intermediate risk, p= 0.027), presence of Ph chromosome (p= 0.0002), CNS disease at diagnosis (p= 0.0046), and response to first chemotherapy (p= 0.0032). There were no differences in overall survival according to age, gender, Hispanics vs. other ethnic groups, immunophenotype (B vs. T ALL), WBC count, presence of CD10, CD34, and myeloid markers. Also, the choice of chemotherapy regimen did not impact survival significantly.

Conclusions: This cohort of patients revealed a predominance of younger male adults (median age 31 years), Hispanics (54%) and high-risk disease (56%). Remission rate after induction was 84% and early death rate (6%), comparable to those reported in the literature. 50% of responders relapsed after a median TTR of 12 months. No factors were found to impact the TTR significantly. Median survival was 16 months lower than historical cohort (30 months). Cytogenetics, Ph +, CNS disease at diagnosis and response to chemotherapy had a significant impact on survival but not on TTR. More investigation of factors which affect long-term outcome in minority population is needed.