Clinical Feature and Prognosis of 60 Patients Presenting Graft Failure (GF) after Allogeneic Stem Cell Transplantation (SCT).
Authors: Hagihara Maki , Kanamori Heiwa , Yoshiba Fumiaki , Aotsuka Nobuyuki , Tanaka Masatsugu , Mori Takehiko , Nakaseko Chiaki , Fujisawa Shin , Sakura Tohru , Uehara Taeko , Kawai Nobutaka , Matsushima Takafumi , Machida Shinichiro , Makita Hisashi , Maruta Atsuo , Sakamaki Hisashi 
Published: October 2019

Abstract
Background: GF after allogeneic SCT is a life-threatening event. To clarify the clinical feature of patients with GF and the feasibility of second SCT for GF, we retrospectively investigated the patients who developed GF after SCT.
Patients and Methods: we surveyed adult patients who received SCT in KSGCT between January 1994 and December 2005. Primary and Secondary GF were defined as a failure of absolute neutrophil count (ANC) ≥ 0.5x109/l for at least 3 consecutive days and a decrease of ANC < 0.5x109/l for at least 7 days consecutive days after initial engraftment, respectively.
Results: Of the 1,963 patients, 60 patients (3.1%) were identified with GF. Their median age was 47 years (range, 16 to 63). There were 52 patients with hematological malignancies and 8 with aplastic anemia. The incidence of GF according to donor source was 9/597 patients (1.5%) in related donor-bone marrow (RBM), 1/359 (0.3%) in related donor-peripheral blood stem cells (RPBSC), 18/839 (2.1%) in unrelated donor-bone marrow (UBM), and 32/168 (19%) in unrelated cord blood (UCB). GF in UCB was significantly higher than that in other donors (P<0.001). Primary GF and secondary GF were 45 patients (2.2%) and 15 (0.7%), respectively. In comparison between patients developing primary GF and those developing secondary GF, UCB transplant (69% vs 7%, P<0.005), malignant disease (98% vs 53%, P<0.005), high risk at transplant (61% vs 13%, P=0.009), and HLA mismatch (76% vs 13%, P<0.005) were significant risk factors. Overall survival (OS) at 3 years was 18% in all patients with GF. Of the 60 patients, 33 patients (55%) underwent second SCT. The median interval between the first and second SCT was 49 days (range, 18 to 1204). Second SCT were performed with RPBSC in 12 patients, UBM in 4, and UCB in 17. Conditioning regimen were non-myeloablative in 29 patients, myeloablative in 2, and no conditioning in 2. Total body irradiation (TBI) was used in 11 patients. Bone marrow engraftment after second SCT was obtained in 22 patients (67%) and one third of the patients again experienced GF. Engraftment in patients with TBI (2–12 Gy) was significantly better than that in those without TBI (100% vs 50%, P=0.004), although there were no difference in donor sources, underlying diseases and use of antithymocyte globulin. OS at 3 years in patients with second SCT and in the others without second SCT was 53% and 9.1%, respectively (P=0.005), Major cause of death in both group was infectious complications.
Conclusions: High frequency of GF in patients with UCB was confirmed. It was not clear which donor source is better for second SCT in patients presenting GF, but conditioning regimen including TBI might contribute to obtain engraftment in this setting.