Prephase Rituximab Followed By Cladirabine in Newly Diagnosed Hairy Cell Leukaemia: A Tertiary Care Center Experience from North India
Authors: Panda Tribikram , Singh Reema , Halder Rohan , Palatty Roy , Tikare Nakul , Bhatnagar Sakshi , Ahmed Rayaz , Agrawal Narendra , Bhurani Dinesh 
Published: December 2024

Hairy cell leukaemia (HCL) is a progressive low grade non-Hodgkin's lymphoma usually presents with massive splenomegaly, cytopenias and infective complications. Poor performance status with co-existent infections presents a major challenge for upfront purine analogue based chemotherapy especially in a developing country point of view. Rituximab added to standard Cladirabine has shown to have additional efficacy in MRD eradication even in Cladirabine resistant cases (Maevis V et al 2014). We hereby share our experience of combining Rituximab before Cladirabine based regime in newly diagnosed HCL patients treated at our centre.

Retrospective data was collected during last 15 years from electronic medical records. A total of 50 HCL patients were identified and included for analysis. Baseline clinical, laboratory parameters with treatment details were recorded. Overall survival (OS) and disease-free survival (DFS) were calculated using Kaplan Meier curves.

The median age of presentation was 55.5 years (range 29-77) [male: female 5.2:1]. 32% had eastern cooperative oncology group (ECOG) performance score ≥2. Most common presenting complaints were: fatigue (78%), fever (68%), weight loss (48%), abdominal fullness/awareness of mass (40%). Baseline infection was found in 58% patients. Hepatomegaly, Splenomegaly, and lymphadenopathy were reported in 34%, 78% and 12% patients respectively. Median duration of symptoms was 67.5 days (range 10-730). Anemia (median hemoglobin 8.8 gm/dl), leucopenia (median total leucocyte count 3.2×109/L), thrombocytopenia (median platelet count 62×109/L), monocytopenia, pancytopenia were found in 72%, 62%, 96%, 90% and 28% patients respectively. Median percentage of hairy cells in peripheral blood and bone marrow were 2% (range 0-87) and 46% (range 1-94) respectively. Most common pattern of marrow infiltration was diffuse (85.11%) followed by interstitial (10.64%).

Rituximab (4 weekly cycles, 375 mg/m2) followed by Cladirabine was received by 22/47(46.8%) patients. 16(34.03%) and 6(12.8%) patients received only Cladirabine, and Rituximab alone respectively. Median time to start therapy was 8 days (range 1-129). Three patients lost to follow up, and 5 patients died (2 before starting therapy, 2 after therapy due to infective complications, and 1 due to progressive disease). Response evaluation of 45 patients was done: complete response (CR) 39/45 (86.6%), partial response (PR) 3/45(6.7%) and stable disease (SD) 3/45(6.7%). Median time to CR was 114 days (range 20 - 268). Seven cases relapsed after a median duration of 934 days (range 202 - 2860). Out of 22 patients receiving Rituximab followed by Cladirabine 21 patients achieved CR, and 2 patients had a relapse at day +934 and day +2860. Median duration of follow up was 4.6 years (range 0.03 - 16.3).Five-year OS was 88.7% and 5-year DFS was 79.6% for the entire cohort (median OS, DFS not reached). Five years OS for R+Cladirabine (n=22) is 95.5% and for others treated with only Cladirabine (n=18) is 100% with p-value of 0.11. Five years DFS for R+Cladirabine is 93.3% and for others is 71.8% with p-value of 0.47. Six patients had tubercular reactivation requiring initiation of Anti-tubercular therapy. Univariate analysis for age, performance score, hemoglobin, total leucocyte count, total platelet count, duration of symptoms, splenomegaly and baseline infections for OS and DFS didn't show any significant associations. We didn't evaluate any of our patients for routine post treatment Measurable residual disease (MRD) analysis.

Prephase Rituximab followed by Cladirabine is safe, effective with comparable OS and better DFS (statistically insignificant). It promptly ensures treatment with better control of systemic disease burden without need for any long term initial admission, gives time to patients family for decision. It's a feasible therapeutic option in frail patients with baseline Infection and co morbidities especially from a developing country perspective.