What Contributes to Delayed Engraftment After Autologous Hematopoietic Cell Transplantation?

Author(s):

A recent study identified the pretransplant characteristics contributing to delayed engraftment (DE) following autologous hematopoietic cell transplantation (AHCT).

DE after allogenic transplant is well described, but the authors said they conducted this study because the incidence and clinical characteristics associated with prolonged cytopenias in those receiving AHCT is not well known. The authors said it was the first study to report on these pretransplant factors that contribute to DE.

The retrospective study was carried out at 1 institution from January 1996 to August 2016. The initial cohort included 1162 consecutive patients undergoing AHCT.

While there is no universal definition of DE, the researchers said that other studies have identified DE as platelets below 50,000/µL or an absolute neutrophil count (ANC) count of 150—1000/mm³or less. In this study, DE was identified as platelet count  50,000/µL or less, hemoglobin 8 g/dL or less, or absolute neutrophil count (ANC) 1000/mm³or less starting at 30 days after infusion of autologous hematopoietic cells. The persistence of DE was evaluated at 3, 6, and 12 months after AHCT in all patients who had DE at 30 days.

The median patient age was 57, mostly male, and mostly white. In order of frequency, the patients had multiple myeloma (MM, 59.0%), followed by non-Hodgkin lymphoma (NHL, 18.0%), Hodgkin disease (HD, 12.0%), acute myeloid leukemia (AML, 2.0%) and other diseases. The rate of DE by disease at 30 days was 73.9% (n = 15) for AML, 29.5% (n = 38) for HD, 10.1% (n = 67) for MM, and 51.7% (n = 101) for NHL.

At day 30 after AHCT, 263 of 1162 (22.6%) patients met the criteria for DE. Of these 263 patients, 39 (14.8%) were excluded due to a history of more than 1 AHCT (n = 20), loss to follow-up within 1-year of AHCT (n = 17), and relapse within 30 days (n = 2). Analysis was performed on the remaining 224 patients.

Of the 224,181 (80.8%) patients had DE solely due to low platelet count 30 days after AHCT. Three (1.3%) had DE due to low hemoglobin level, and 40 (17.9%) were due to both low hemoglobin and platelets. All patients had ANC > 1000/mm³. Of these 224 patients, 111 (49.6%) continued having DE at 3 months after AHCT with 102 (91.9%) because of low platelets alone.

At 6 months and 12 months after AHCT, 54 (24.1%) and 17 (7.6%) patients had DE due to platelets alone, respectively. Of those with delayed engraftment at 30 days, by 12  months, 23 (10.3%) had relapsed and 17 (7.6%) were deceased.

The authors said that age had no effect on engraftment, but higher weight did, which suggests that weight loss due to aggressiveness of disease, prolonged chemotherapy, or malnutrition may predict DE, or that heavier patients will receive a greater number of cells. The role of weight loss on engraftment after AHCT needs additional study, the researchers said.

Another finding that needs additional study is that the black patients in the group were more likely to engraft at 3 months compared with white patients. This finding was curious, since black patients were underrepresented in the study and made up only 7.5% of all patients.

NHL patients were more likely to have DE compared with those with MM; fewer than half of patients with NHL engrafted at 1 month. NHL patients had the highest median CD34⁺ cell dose; this may mean that there is a characteristic of NHL and/or the patient that makes DE more likely, the authors said.

In addition, conditioning regimen and pretransplant cytomegalovirus (CMV) status had no association with engraftment status.

But maintenance therapy for MM and lymphoma was associated with DE, with 85% of patients receiving maintenance therapy having DE at 3 months. Although there was no significant impact of pretransplant white blood count, hemoglobin, and hematocrit on DE, patients with higher pretransplant platelet count had significantly lower chance of DE in both univariate (P  <.001) and multivariate (P = .001) analysis. Transfusion dependence prior to AHCT was also a statistically significant predictor of DE at 3 months (P = .0083).

The study identified that transfusion dependence prior to AHCT, pre-AHCP platelet count, and CD34⁺ cell dose were the strongest predictors of DE.

Reference

Lutfi F, Skelton WP, Wang Y, et al. Clinical predictors of delayed engraftment in autologous hematopoietic cell transplant recipients [published online October 10, 2019]. Hematol Oncol Stem Cell Ther. doi: 10.1016/j.hemonc.2019.08.003.