Decade-Long Experience in Leukemia Treatment amidst Resource Constraints: Insights from Pakistan
Authors: Anwar Nida , Abid Madiha , Jamal Aisha , Rizvi Quratulain , Saleem Ali , Farzana Tasneem 
Published: December 2024

INTRODUCTION
Need for comprehensive cancer care, including prevention, diagnosis, and management, is pressing in Pakistan, where an estimated 63,415 men and 85,590 women are diagnosed with cancer annually but incidence rates for leukaemia are challenging to determine due to lack of comprehensive registry. Acute myeloid leukaemia (AML) imparts significant challenges in developing countries with limited diagnostics and treatment funding. Acute lymphoblastic leukaemia (ALL) commonly diagnosed in children also poses challenge in adults and young adolescents with early chemotherapy response critical for prognosis. Primary ObjectiveOutline treatment experience at one of Pakistan's largest haematology referral centre.Secondary ObjectiveHighlight efforts in capacity building despite ongoing challenges.

METHOD
The study analysed records for 835 acute leukaemia patients focusing on the treatment experience of 331 who received curative treatment from January 2012 to January 2024 at National Institute of Blood Disease and BMT (NIBD) Pakistan after the approval of institutional review board under declaration of helsinki. For AML, intensive treatment (3+7), hypomethylators plus venetoclax, with best supportive care (blood transfusion and anti microbials) was given. ALL patients underwent intensive treatment, metronomic (less intensive) protocols. Post intensive induction, patients in remission proceeded to consolidation with HiDAC/IDAC, and 98 (29.6%) eventually underwent hematopoietic stem cell transplantation (HSCT). Until 2018, UKALL2003 was used, followed by the UKALL 2011 induction B protocol post-2018.
RESULTS
A total of 331 patients were included, 219 (66.2%) had AML and 112 (33.8%) had ALL.
In AML with median-IQR [26.5(18.25)], 187 (85.4%) underwent intensive treatment while 32 (14.6%) received treatment with hypomethylator and venetoclax. Ninety-six (43.8%) underwent complete remission(CR) whereas 123(56.2%) did not achieved remission in which 40 (18.3%) passed away at the time of induction treatment whereas 32(14.6%) had primary refractory disease(PRD) in which 20 patients subsequently expired, and 51 (23.28%) were lost to follow (LTF). Out of 96(43.8%), 32(14.6%) were consolidated with HIDAC/IDAC whereas 64 individuals (29.2%) underwent HSCT. In post transplant patients, transplant-related mortality (TRM) was observed in 36(56.3%) and relapse in 19(29.6%). Relapsed free survival (RFS) and overall survival (OS) was found to be 9(14.1%) and 83(46.4%).
Out of the 112 ALL patients with median-IQR [34(16)], 72 (64.3%) underwent intensive treatment, 40 (35.7%) received metronomic (less intensive treatment). Fifty-eight (51.7%) achieved CR in which 34(30.35%) underwent HSCT whereas 24(21.4%) were proceeded for consolidation. Out of 54(48.2%) who did not achieved remission, 10 (8.9%) had PRD; 40(35.7%) passed away and 4 (3.5%) were LTF. Post transplant, TRM was observed in 19 (55.9%), and relapse in 12 (35.9%). RFS and overall survival OS was found to be 3(8.8%) and 53 (47.3%).

CAPACITY BUILDING
Established dedicated campus (PECHS) for haematological malignancies, with trained team including nurses, clinical pharmacists, and infection control specialists. Transitioned ALL treatment from inpatient induction to day care basis after training staff in critical aspects of hemodynamics and febrile neutropenia. Implemented hypomethylator treatment protocols on an outpatient basis. Established a clinical pharmacy fellowship program in malignant haematology. Secured government funding for 265 patients, marking the first instance of government-supported treatment at a private organisation. Engaged with Pakistan's Bone Marrow Transplant Working Parties for AML and ALL. Training for fellows by remote mentorship (ASH-VTP, IDEA-ASCO) Ongoing efforts to establish registry, address gaps, overcome challenges, with future expansion to Lahore, Sukkur campus and Hyderabad outreach centre.

CONCLUSION
Pakistan, as a developing country with a large population and varied socioeconomic backgrounds, faces significant challenges in cancer management due to insufficient resources and limited funding. Our study highlights need for continuous improvement in treatment protocols and patient management, noting the progress in remission rates and the ongoing difficulties associated with treatment complications in leukaemia patients.