Maryam Khan, Shafaq Abdul Samad, Sadaf Altaf, Danyal Ghani, Shahzad Sarwar, Qamar Un Nisa Chaudhry, Syed Kamran Mehmood, Tasneem Farzana, Uzma Zaidi, Natasha Ali, Nighat Shahbaz, Mehreen Ali Khan, Kashaf Ad Duja Awais, Salman Adil, Muhammad Ayaz Mir, Tariq Ghafoor, Tariq Azam Khattak, Aliya Batool, Syed Nasir Abbas Bukhari, Sana Khurram, Tariq Mahmood Satti, Hira Tariq, Parvez Ahmed, Raheel Iftikhar
MSD-HSCT achieves durable survival for AA patients in resource limited settings. Early referral strategies, infection control and optimization of graft characteristics are required to improve survival in these settings.
BACKGROUND: Haematopoietic stem cell transplantation (HSCT) from an HLA-identical sibling is the primary curative therapy for acquired aplastic anaemia (AA). Outcomes from large cohorts in low- and middle-income countries are scarce.
OBJECTIVES: To evaluate survival outcomes of patients with acquired aplastic anemia undergoing matched sibling donor (MSD) HSCT in Pakistan and to identify key transplant- and patient-related factors influencing outcomes in a resource-limited, low- and middle-income country (LMIC) setting.
STUDY DESIGN: Multicenter retrospective cohort study.
METHODS: We retrospectively analysed 596 consecutive patients with acquired AA who underwent HSCT from an HLA-identical sibling donor at seven Pakistani centres between January 2001 and August 2023. Patients receiving haploidentical, unrelated or other alternative-donor grafts were excluded. Overall Survival (OS) was estimated using Kaplan-Meier method. Univariable and multivariable Cox regression identified predictors of OS; logistic regression identified predictors of graft failure.
RESULTS: Median age at transplant was 18 years (IQR:13-24), median time to neutrophil and platelet engraftment was 12 days (11-14 days) and 19 days (14-28 days) respectively. Primary graft failure occurred in 39 (6.6%) and secondary graft failure in 52 (8.8%) patients. Incidence of acute and chronic graft versus host disease (GVHD) was 70 (11.2%) and 97 (19%) respectively. At a median follow-up of 59.4 months (95% CI 47.9-68.4), OS was 69.6 %. The leading cause of mortality was graft failure and poor graft function in 91 (49.4%) followed by sepsis in 60 (32.6%) patients. On multivariable Cox regression, RCC <20 (adjusted HR 0.43, 95% CI 0.25-0.73, p=0.002), CSA+MMF prophylaxis (adjusted HR 2.57, 95% CI 1.47-4.51, p=0.001), and BMH+PBSC stem cell source (adjusted HR 0.61, 95% CI 0.36-, p=0.001) were independent predictors of OS.
CONCLUSION: MSD-HSCT achieves durable survival for AA patients in resource limited settings. Early referral strategies, infection control and optimization of graft characteristics are required to improve survival in these settings.