Incidence, Risk Factors, and Outcomes of Primary Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for both malignant and nonmalignant hematologic disorders. However, primary poor graft function (PGF) is a serious early complication of allo-HSCT that leads to a poor outcome. Little is known about the characteristics, incidence, and risk factors of primary PGF occurring after allo-HSCT. Here we performed a 1:4 ratio nested case-control study in 830 patients who underwent allo-HSCT between April 2013 and November 2018 at our center. Twenty-four patients (14 males and 10 females; average age, 35.79 years; range, 17 to 53 years) developed primary PGF. On univariate and multivariate analyses, a CD34 + cell dose <5 £ 10 6 /kg (P = .003), a serum ferritin (SF) level >2000 ng/mL (P = .008), and splenomegaly (P = .039) were identified as 3 independent risk factors for primary PGF. After a median follow-up of 7.5 months (range, 1 to 48 months), only 5 patients (20.8%) survived. The survival rate of patients with primary PGF was significantly lower than that of patients with good graft function (GGF) (1-year overall survival, 25.0% versus 90.6%; P < .001). Cox regression analysis suggested that PGF and high SF level were strongly associated with rapid death in these patients. In conclusion, allo-HSCT recipients with a low CD34 + cell dose in their graft and exhibiting a high SF level and splenomegaly should be monitored for the development of primary PGF after allo-HSCT, and effective therapies need to be explored.

Advances in the understanding of poor graft function following allogeneic hematopoietic stem-cell transplantation

“…A recent study, identified the SF level >2000 ng/ml as an independent risk factor for primary PGF (OR = 4.147; 95% CI: 1.452–11.845; p = 0.008), and the patients of SF level >2000 ng/ml had a poor 1-year overall survival. 3 …”

“…Splenomegaly is reportedly another risk factor of primary PGF, 3 , 20 , 21 although the underlying diseases are heterogeneous. The possible mechanism might be that enlarged spleen could trap and destroy hematopoietic cells.…”

“…However, most recent studies have defined PGF based on the severity of cytopenia of at least two cell types: (1) absolute neutrophil count (ANC) ⩽0.5 × 10 9 /l; (2) platelet (PLT) count ⩽20 × 10 9 /l; and (3) hemoglobin (HB)⩽70 g/l for at least 3 consecutive days beyond day +28 post-HSCT or the requirement of transfusion support with hypoplastic-aplastic bone marrow, excluding severe graft versus host disease (GVHD) and relapse. 2 – 4 Primary PGF refers to incomplete engraftment, while secondary PGF is defined as a loss of initial engraftment. Patients with primary PGF have a lower response rate to treatment and poorer prognosis compared with those with secondary PGF.…”

“…5 PGF is a life-threatening complication, and the survival rate is significantly lower than patients with good graft function (GGF). 3 , 4 This is because persistent leukocytopenia and thrombocytopenia increase the risk of infections and bleeding, and, thus, raise the mortality rate. The incidence of PGF is approximately 5–27% 3 , 5 and has become a growing obstacle after allo-HSCT due to the development of haploidentical-HSCT.…”

“… 3 , 4 This is because persistent leukocytopenia and thrombocytopenia increase the risk of infections and bleeding, and, thus, raise the mortality rate. The incidence of PGF is approximately 5–27% 3 , 5 and has become a growing obstacle after allo-HSCT due to the development of haploidentical-HSCT. However, the underlying mechanism has yet to be elucidated, while treatments are very limited.…”