Second allogeneic hematopoietic cell transplantation for graft failure: Poor outcomes for neutropenic graft failure

Abstract

Purpose Graft failure (GF) after hematopoietic cell transplant (HCT) occurs in 5 – 30% of patients. GF can be accompanied by neutropenia (NGF) or can result with adequate neutrophils, but loss of donor chimerism (non-neutropenic graft failure, NNGF). In this report we describe the outcomes of 95 patients treated with a second HCT for GF at the University of Minnesota; 62 with NGF and 33 with NNGF. Findings The cumulative incidence of neutrophil recovery at 42 days after second HCT was 45% for NGF and 88% for NNGF. A second GF occurred in 34 NGF (55%) and in 9 NNGF (27%) patients. The incidence of grade III–IV acute graft versus host disease (GVHD) was 8% (95% confidence interval (CI), 1 – 16%) and 12% (95% CI, 1 – 23%) for NGF and NNGF, respectively. From the 2nd HCT, 1-year overall survival (OS) was 44% (95% CI, 34 – 54%), [NNGF: 76% (95% CI, 57 – 87%) and NGF: 27% (95% CI, 17 – 39%)]. The most common cause of death after second HCT was infection (52%). Conclusions In summary, the outcomes of second HCT after NGF and NNGF are different with much worse outcomes for NGF necessitating new approaches for this complication.

Non-myeloablative conditioning for second hematopoietic cell transplantation for graft failure in patients with non-malignant disorders: a prospective study and review of the literature

“…Many regimens used for second HCTs have resulted in poor engraftment and high mortality. Repeat conditioning with fully myeloablative preparative regimens produces unacceptable organ toxicity and risk for overwhelming infections, especially in patients with NGF 9 . Thus, use of a RIC regimen for second HCT represents an attractive and less toxic means of rescue.…”

“…By permitting mixed or progressive donor engraftment, RIC HCTs avoid the anticipated prolonged period of aplasia associated with more intensive myeloablative regimens. A major concern with using RIC regimens for salvage HCT has been an increased rate of second GF, which is of particular concern in a patient who has previously experienced GF following first transplantation 9 . Our NMA conditioning regimen utilizes fludarabine to provide appropriate immunosuppressive conditioning; while combination of low dose busulfan and low dose TBI allows for adequate myeloablation to ensure engraftment.…”

“…In general, “primary GF” is used to describe the scenario of insufficient donor derived hematopoiesis by post-transplant day +42. Primary GF can be further stratified into neutropenic GF (NGF, the absence of neutrophil recovery prior to day +42) or non-neutropenic GF (NNGF, predominant autologous hematopoietic recovery prior to day +42) 9 . In contrast, secondary GF is defined as the loss of donor cells following initial donor engraftment.…”

“…In contrast, secondary GF is defined as the loss of donor cells following initial donor engraftment. Autologous recovery is common in patients with non-malignant disorders who develop secondary GF, however late marrow aplasia and pancytopenia may also develop resulting in either NNGF or NGF subtypes of secondary GF, respectively 9 .…”

Outcome following second allogeneic hematopoietic cell transplantation: A single‐center experience

“…11 Previous retrospective studies however have demonstrated a generally poor outcome following second transplant for graft failure. [12][13][14] Data concerning second allogeneic HCT in the literature are scarce and are generally limited to retrospective studies with limited numbers of patients. The purpose of this study was to retrospectively investigate the parameters that influence post-second allogeneic HCT survival at our center, as well as to characterize the post-transplant course of survivors in regard to post-transplant complications and performance status.…”