Patterns of Care and Outcomes of Adults ≥ 40 Years of Age with Newly Diagnosed Acute Lymphoblastic Leukemia (ALL): A Multicenter Registry Analysis from India
Authors: Jain Punit , Jain Hasmukh , Sarma Rup Jyoti , Kulkarni Uday , Karunakaran Parathan , Ganguly Shuvadeep , Ganesan Prasanth , Lk Rajeev , Damodar Sharat , Kapoor Rajan , Palassery Rasmi , Krishnan Unni , Roshan Reshma , Chozakade Aakash , D Aravind , Samuel Prasanna , Prakash Om , Mathews Vikram , Sengar Manju 
Published: December 2024

Introduction:
Survival outcomes in adults aged ≥ 40 years with acute lymphoblastic leukemia (ALL) are dismal at around 30% in clinical trial settings. Limited information exists on the outcomes and patterns of care in developing countries like India. The Hematology Cancer Consortium (HCC: https://www.hemecancer.org/) is a prospective registry that captures information on hematological malignancies across multiple centers in India. We analyzed the patterns of care and outcomes of adult ALL from the registry.
Methodology:
The study included all newly diagnosed ALL (age ≥ 40 years) from January 2019 to January 2021 entered into the database from twelve participating centers. Descriptive statistics were used to summarize the baseline characteristics and responses. The Kaplan-Meier (KM) method was used to analyze the survival outcomes, and the log-rank analysis was used to compare the different ALL subgroups.
Results:
261 adults aged ≥ 40 years with ALL were registered in the study period. Out of these, 92 patients refused therapy at the primary center due to financial limitations (n=21; 22.8%), poor performance status (n=25; 27.5%), referral to another center (n=29; 31.5%), or other reasons like apathy towards treatment (n=2; 2.2%), socio-cultural barriers (n=5; 5.4%) and few unknown causes. Of the 169 patients who received therapy, the age distribution was 40-49 years (n=100; 59.2%); 50-59 years (n = 51; 30.2%); ≥ 60 years (n =18; 10.7%). Of these, there were 105 males (62.1%). Extramedullary disease was seen in 32 patients (18.9%) at diagnosis [Testis (n=1); Mediastinum (n=6); Central nervous system (CNS) (n= 25)]. The median white blood cell count at baseline was 9.2 x 109 cells/Lt; 141 (83.4%) patients were classified as B ALL, and 28 (16.6%) had a T ALL. Genetic studies include conventional karyotype (n=105; 62.1%), FISH (n=75; 44.3%), PCR (n=110;62.7%), and ploidy analysis (n=113; 66.8%). Significant genetic abnormalities included hyperdiploidy (n = 16/113; 14.1%), t(12;21) (n = 3/53; 5.6%), and t(1;19) (n = 4/53; 7.5%). Bcr abl fusion abnormality was seen in 48 (28.4%) patients.
The BFM-type regimen was the most common protocol in 163 (96.4%) patients. HyperCVAD was offered to 6 (3.5%) patients. Imatinib (n=16) and dasatinib (n=27) were the only two tyrosine kinase inhibitor (TKI) drugs used to treat bcr-abl-positive patients (n=43/48; 5 patients did not receive TKIs). Serious induction toxicities included pneumonia (n=34; 20.1%), tumor lysis syndrome (n=24; 14.2%), gram-negative sepsis (n=16; 9.4%), and venous thrombosis (n=7; 4.1%). Initial induction mortality was seen in 37 (21.8%) patients. Post-induction bone marrow assessment was available in 121 patients (71.6%), with a complete morphological remission rate of 101 (101/169, 59.7%). The minimal residual disease assessment (MRD) by flow cytometry at end induction was available in 87 patients, with 35 (40.2%) being MRD positive and 52 (59.7%) being MRD negative. Seven patients underwent an allogeneic stem cell transplant (n=6 in CR1; n=1 in CR2) [matched sibling donor transplants (n=6); haploidentical transplant (n=1)]. Forty-four patients (n=27.2%) relapsed [CNS (n=4), medullary (n=40)]. At the last follow-up, a total of 70 patients (41.4%) had died [progressive disease (n = 38), infection (n=17), others (n=15)], 44 (26%) were lost to follow-up, and 39 (23%) were alive and on follow up.
With a median follow-up of 15 months, the one-year O.S. was 53.8%. [B cell ALL-56.2%; T cell ALL-42.3% (p-value=0.093)] and the one-year P.F.S. was 48.1%. [B cell ALL-50.7%; T cell ALL-35.1% (p-value=0.084)]. With a median follow-up of 27 months in bcr abl-positive disease who received TKI (n=43), the one-year O.S was 68.5% and the one-year P.F.S was 66.3%.
Conclusions:
Outcomes of older adults with ALL in India remain dismal. Patients with Philadelphia positive B ALL receiving TKIs tend to do better. High rates of induction mortality, infections, attrition, and limited treatment options after relapse remain significant causes of morbidity and mortality in ALL treatments.