Graft failure in cord blood transplantation successfully treated with short-term reduced-intensity conditioning regimen and second allogeneic transplantation

Abstract

Graft failure (GF) remains a major problem in cord blood transplantation (CBT). In 36 adult patients undergoing CBT at our hospital between July 2003 and December 2009, six patients developed GF (primary, n = 5; secondary, n = 1). All six patients underwent second stem cell transplantation (SCT). Three patients had acute myeloid leukemia, one had acute lymphoblastic leukemia, one had chronic myeloid leukemia, and one had aplastic anemia. Five patients were complicated with sepsis before the second SCT. The median elapsed time from first CBT to the diagnosis of primary GF was 27 days. Secondary GF was diagnosed on day 567. The median elapsed time from primary GF to second SCT was 9 days. In the patient with secondary GF, the elapsed time was 35 days. Cord blood grafts were used in 5 patients and a matched sibling donor in one patient. All 6 patients underwent second transplantation following a modified '1-day'-based preparative regimen consisting of fludarabine (30 mg/m(2), 1 day, n = 2; 2 days, n = 1; 3 days, n = 3), cyclophosphamide (2 g/m(2)), and total body irradiation (2 Gy). All patients achieved neutrophil engraftment, and the median elapsed time from second SCT to engraftment was 35 days. Four patients remain alive between 5 and 38 months after second SCT. '1-day'-based short-term conditioning may be a promising salvage regimen.

Salvage allogeneic hematopoietic SCT for primary graft failure in children

“…The incidence of graft failure is assumed to range from 2 to 20%, and the frequency depends on various factors such as stem cell source 1,2 and preconditioning regimen, [3][4][5] underlying disease, 5 HLA disparity 2,6,7 and the presence of anti-HLA Abs. 8 Salvage HSCT can rescue pGF patients, [9][10][11][12][13][14] and recent studies on adult pGF patients have showed the feasibility of using reduced-intensity conditioning containing fludarabine (FLU) and low-dose irradiation, 13,[15][16][17] including short-term preconditioning regimen 10,18 and an advantage of PBSC as the stem cell source for salvage HSCT. 19,20 However, the management of pGF patients is usually difficult because of their poor clinical status.…”

Potency, Proliferation and Engraftment Potential of Stem Cell Therapeutics: The Relationship between Potency and Clinical Outcome for Hematopoietic Stem Cell Products

“…Since potency assay could only be completed on 25 samples and two of those would not have been released for transplantation purposes, the accuracy of the assay was approximately 92%. It has been shown that between 15 and 20% of all cord blood stem cell transplants do not engraft [27][28][29]. From the results described here, it would appear that this high percentage rate of graft failure could be reduced by at least 10% thereby significantly improving efficacy and reducing unnecessary risk to the patient.…”

“…Results can be documented either as a "growth-no growth result" or the total number of colonies is counted, but only reported as the number of granulocyte-macrophage (GM) colonies. The focus is on the number of GM colonies produced since this correlates with time to neutrophil engraftment [52,53,28]. The growth factor cocktail used mostly for these assays include Erythropoietin (EPO), Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF), Interleukin-3 (IL-3) and Stem Cell Factor (SCF).…”

“…The reason for the high engraftment failure has been attributed to low cord blood unit potency [28]. This, in turn, has been assumed to be a problem with the tests and assays used to characterize the cells.…”

Feasibility of salvage cord blood transplantation following fludarabine, melphalan and low-dose TBI for graft rejection after hematopoietic stem cell transplantation

“…Previous case series reported the promising results of salvage CBT following a 1-day regimen, which is presumed to be the minimum intensity conditioning to shorten the neutropenic period and ensure engraftment. [9][10][11] However, this shortened conditioning may require careful clinical management because the intensity of reconditioning was largely dependent on the discretion of attending physician. The intensity of conditioning necessary for donor cell engraftment needs to be investigated in-depth by time course analysis of chimerism and immunocompetent cells.…”