Comparative Analysis of Corrected Total Nucleated Cells (TNC) versus CD34 Counts and Their Impact on Graft Outcomes in Allogeneic Bone Marrow Transplant: A Study in a Resource-Limited Setting

Abstract

Background: Bone marrow transplantation (BMT) is considered the standard of care for many hematological malignant and nonmalignant diseases. It involves infusing of hematopoietic stem cells (HSCs) of a compatible donor to a patient after the administration of conditioning therapy with the objective of reconstructing the patient’s hematopoietic system.

Objective: To evaluate whether TNC counts can serve as a viable alternative to CD34+ enumeration for predicting transplant outcomes in settings lacking advanced cell selection technologies.

Study Design: This is a retrospective design study.

Duration and Place of the study: This research was conducted at a Gambat Institute of Medical Sciences between 2^nd, January 2019 to 1^st, February 2024.

Material and Methods: This retrospective study analyzed 84 consecutive allogeneic bone marrow transplant recipients (55 males, 29 females; age range 7-62 years) at Gambat Institute of Medical Sciences between January 2019 and February 2024, comparing outcomes between CD34-selected (n=44) and TNC-based (n=40) grafts. Using complete clinical records, we evaluated engraftment kinetics (time to ANC >500/?L for 3 consecutive days), GVHD incidence (graded by Glucksberg and NIH criteria), and survival outcomes (1- and 3-year overall and disease-free survival), with statistical analysis performed using SPSS version 26.0 (?² and t-tests for categorical and continuous variables respectively; significance at p<0.05)

Results: The study comprised of 84 patients, of which 55 were male and 29 were female, with the mean age in CD34 and TNC group were 35.2 years, and 36.1 years (p=0.68), respectively with similar distribution according to prescribed range of ages (p=0.56).

The CD34 count was 5.1 x 10^6/kg in the CD34 group, and the corrected TNC count was 3.5 x 10^8/kg, with no differences between the groups (p=0.75). Infusion volumes were similar, with 250 mL in the CD34 group and 245 mL in the TNC group (p=0.62). Time to neutrophil and platelet engraftment was also comparable between the groups (p=0.58 and p=0.66, respectively). Rates of graft-versus-host disease (GVHD) were similar in both groups. The incidence of acute GVHD (Grade I-II) was 22.7% for the CD34 group and 35.0% in the TNC group, while chronic GVHD occurred at rates of 18.2% and 25.0% respectively (p=0.42). The CD34 cohort had longer median GVHD-free survival (59.1% vs. 40.0%, p=0.09). Engraftment outcomes showed successful engraftment in 86.4% of the CD34 group and 80.0% in the TNC group (p=0.42). The median time to engraftment was 16 days in the CD34 group and 17 days in the TNC group (p=0.55) . Primary graft failure occurred in 9.1% of the CD34 group and 15.0% of the TNC group (p=0.42), while secondary graft failure occurred at similar rates (4.5% vs. 5.0%, p=0.91). Overall survival and disease-free survival rates were similar between the groups. The 1-year overall survival was 79.5% in the CD34 group and 70.0% in the TNC group (p=0.31), while the 3-year overall survival rates were 68.2% and 60.0% respectively (p=0.40). The 1-year disease-free survival rates were 75.0% and 65.0% in the CD34 and TNC groups (p=0.33), with 3-year rates of 63.6% and 55.0% respectively (p=0.44). The median follow-up durations were 24 months for the CD34 group and 22 months for the TNC group (p=0.58).

Conclusion: There were no statistically significant differences between the CD34 and TNC groups in terms of demographics, clinical characteristics; grafts used for transplantation; incidence of acute, and chronic GVHD, engraftment outcomes and survival metrics. For countries where CD34 selection facilities are not available, our findings provide reassuring evidence that corrected TNC transplants can achieve similar outcomes to CD34 selected transplants. This suggests that TNC transplants are a viable and effective alternative, ensuring that patients receive high-quality care and comparable clinical benefits even without access to CD34 selection technology.