Bone Marrow Quality Index: A Predictor of Acute Graft-versus-Host Disease in Hematopoietic Stem Cell Transplantation for Thalassemia

Abstract

Bone marrow continues to be the preferred source of stem cells in allogenic transplantations for non-malignant disorders. Granulocyte-colony stimulating factor (G-CSF)-primed bone marrow (BM) is associated with low rates of acute GVHD and allows reduced collection volumes while ensuring speedy engraftment. However, variability in bone marrow harvest quality is a concern. This report analyses the utility of a novel indicator - Bone Marrow Quality Index (BMQI), which is a ratio of marrow cell count to peripheral blood cell counts, to predict acute GVHD. We analysed 184 consecutive first matched related donor bone marrow transplants for thalassemia using G-CSF-primed bone marrow over 6 years from March-2017 to April-2023 across 2 centres in India. Bone Marrow Quality Index (BMQI) was defined as the ratio of WBC count of G-CSF primed bone marrow to Peripheral WBC count within 24 hours of harvest. EBMT criteria were used for grading GVHD. Log-rank test was used to assess the impact of BMQI on GVHD. Chi-squared test was used to compare categorical data and Wilcoxon test was used to compare the numeric data. Cox proportional-hazards model was used to investigate the association of BMQI vis-à-vis other factors on acute GVHD. Of the 184 patients, 19 had a BMQI <0.9 and 18 between 0.9 and 1. The remaining 147 had BMQI >1. The proportion of patients with acute GVHD grade II-IV was 37%, 22% and 12% respectively for patients who received BMQI <0.9, 0.9-1 and >1 (p= 0.018). Patients who received BMQI <0.9 had a 3.1 times higher chance (95% CI being 0.9 to 10.6) of developing aGVHD II-IV and in those with BMQI 0.9-1 this was 2 times (95% CI being 0.5 to 6.6) higher. BMQI was the significant predictor associated with GVHD hazard (p=0.014). BMQI seems to be the most relevant and controllable predictor of acute GVHD. BMQI is a novel, informative, and very simple indicator which could influence GVHD prophylaxis decision-making. Our indicator is accurately measurable, inexpensive, precise, and timely; further it does not involve any sophisticated equipment, thus may be widely applicable. Prior knowledge of poor marrow quality may help intensify prophylaxis and monitoring for acute GVHD besides triggering review of collection procedures.