Hematopoietic Cell Transplantation Co-Morbidity Index (HCT-CI) to Predict Non Relapse Mortality After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

In recent decades, several advances were made in the management of patients (pts) who underwent allogeneic hematopoietic stem cell transplantation (HSCT). Despite that, the transplant related mortality (TRM) is not negligible. Tools that could predict TRM, based on pre HSCT characteristics and co-morbidities were always sought. Some of these tools are the modified hematopoietic cell transplantation co-morbidity index (HCT-CI).

To apply the modified HCT-CI and correlate it with overall survival (OS) and non-relapse mortality (NRM). Pts and Methods: This analysis include patients who received allogeneic HSCT, for malignant and non malignant hematological diseases, after high or low dose conditioning regimens, from related and unrelated donor, at the HSCT unit of the University Hospital of Campinas between 1993 to 2010. The conditioning regimens and graft versus host disease (GVHD) prophylaxis were selected according to ongoing protocols at the University Hospital. Informed consent for transplant was obtained from all patients. We defined low dose conditioning regimen as follow: busulfan dose < 9 mg/kg, melphalan dose < 150mg/m², and total body irradiation dose of 2Gy. All patients received cyclosporine-A (CsA) with methotrexate or CsA with mycophenolate mofetil as GVHD prophylaxis. Screening for cytomegalovirus with antigenemia and preemptive treatment with ganciclovir were made for all patients. Prophylaxis for Candida infections was made with fluconazole; for bacterial infections ciprofloxacin was used. Prophylaxis for Pneumocystis jirovecii was made with sulfamethoxazole and trimethoprim. For viral agents as herpes simplex virus and varicella zoster virus, acyclovir was used. The diagnosis and clinical grading of acute and chronic GVHD were performed using standard criteria. Information on co morbidities was extracted, retrospectively, from medical charts. Each co-morbidity was assigned an integer weight, based on derived scores from Sorror et al. The HCT-CI score was the sum of this integer weights, and the patients were then assigned to one of the risk groups: 0, 1, 2 and 3 or more. Kaplan-Meier was applied for estimation of overall survival. NRM was estimated by cumulative incidence considering primary relapse disease as competing risk.

457 pts were analyzed at the beginning. However, 331 (72.4%) were evaluable, 126 (27.6%) were excluded when at least one parameter was missing. 208 (63%) were male with a median age of 36.5 (5–65) years, 249 (75%) pts received high dose (HD) conditioning and 82 (25%) low dose (LD). Distribution of diseases in the HD was: 110 (44%) acute leukemias; 109 (43%) CML and 30 (13%) others; LD was: 42 (51%) severe aplastic anemia; 14 (17%) lymphomas; 12 (15%) myeloma and 14 (17%) others. HCT-CI in HD was: 127 (51%) score 0; 39 (16%) score 1; 19 (7%) 2 and 64 (26%) score ≥ 3; in LD 33 (40%) score 0; 14 (17%) score 1; 8 (10%) score 2 and 27 (33%) score ≥ 3. The median follow up in HD was 22 months (0–201) and 9 (0–203) in LD. The adjusted OS at 10 year for HD conditioning according to the HCT-CI was 55% for score 0, 34% for score 1–2 & 34% for score ≥ 3 and for LD conditioning was 58% for score 0, 53% for score 1–2 & 15% for score ≥ 3 (P< 0.0001). The NRM rate in the HD cohort was 32% in the pts with a score 0, 42% for score 1–2 and 53% in the score ≥ 3. In the LD cohort, the NRM was 23% in the pts with a score of 0; 35% for score 1–2 and 54% in the score ≥ 3 (P= 0.002). The adjusted OS for conditioning type in patients with cardiac valve disease was associated to a lower OS (29% and 33% P= 0.002) whereas mild hepatic involvement was just significant in the HD cohort.

The OS and NRM were worse for score ≥ 3 either in HD and LD groups. The heart valve disease emerged as a worse outcome in both conditioning type and mild hepatic involvement only in HD group. The HCT-CI showed to be a valid tool to predict outcome after allogeneic HSCT.

No relevant conflicts of interest to declare.