Allogeneic Transplantation for Patients with Advanced Acute Leukemia: a Single Center Retrospective Study of 92 Patients

Abstract

Allogeneic transplantation is a well recognized treatment strategy of leukemia. However, its use in advanced leukemia patients is a subject of some debate especially when donors are not HLA-identical siblings because of the toxicity and cost of the procedure. We reviewed retrospectively the outcome of patients (pts) who received allogeneic transplantation for advanced acute leukemia in our center between 09/86 and 11/97. Thirty-six pts (study group) who lacked a matched sibling donor received partially matched related donor (n=14: PMRD group) or matched unrelated donor transplantation (n=22: MUD group). Fifteen pts had AML and 21 ALL. Seventeen pts (47%) were in CR>1, 13 pts (36%) had refractory disease and six pts (17.7%) were in untreated relapse. The outcome was compared to that of 56 patients (AML: 45.5 %, ALL: 55.5 %, CR>1: 49.9 %, refractory disease: 37.5 %, untreated relapse 19.6 %) who received allogeneic transplantation from a matched sibling donor (control group). Various conditioning regimens and GVHD prophylaxis were used. The actuarial incidence of grade II to IV acute GVHD was significantly higher in the study group (57%) than in the control group (34%) (p=0.047). The actuarial risk of relapse at three years was 21% +/- 22% in the study group versus 65% +/- 16% in the control group (p= 0.04). The actuarial probability of transplant-related mortality at 3 years is 64 +/- 16% for the study group and 25 +/- 11% for the control group (p=0.001). The leading cause of death in the study group was infection (30%) followed by acute GVHD and relapse. Relapse was the major cause of death in the control group (54%), followed by infection, interstitial pneumonia, veno-occlusive disease and GVHD. The OS and probability of leukemia-free survival at 3 years were 28 % +/- 15% (95% CI) and 27% +/- 15% (95% CI) in the study group. The overall survival and probability of LFS at 3 years were respectively 28 +/- 12% (95% CI) and 23 +/- 12% (95% CI) in the control group (p = 0.08 and p=0.11 respectively). In multivariate analysis, transplant-related mortality was higher in the study group (p=0.04) and lower if both donor and recipient were seronegative for CMV (p=0.007). OS was significantly higher for seronegative couples (p=0.0001), and when CR was achieved before BMT (p=0.0022). These results suggest that all efforts in this field should be directed on lowering the transplant related mortality for non geno-identical transplants and the relapse rate in geno-identical transplants.

Flagellin, a TLR5 Agonist, Reduces Graft-versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplantation Recipients While Enhancing Antiviral Immunity

“…The major causes of mortality in cancer patients treated with allogeneic hematopoietic stem cell transplantation (HSCT) are graft-vs-host disease (GvHD), relapse, and opportunistic infections (1, 2). GvHD is caused by allo-reactive activated donor T cells, in part, through the elaboration of inflammatory cytokines released by host tissues in response to pre-transplant conditioning with radiation and/or high dose chemotherapy (3).…”

Reliable quantification of hematopoietic chimerism after allogeneic transplantation for acute leukemia using amplification by real-time PCR of null alleles and insertion/deletion polymorphisms

“…1,2 Mixed chimerism (MC) increases in patients with acute leukemia who are at high risk for relapse, enabling its anticipation by about 2 months. [3][4][5][6][7] Consequently, the determination of hematopoietic chimerism to monitor grafting and prevent relapse 3,[7][8][9] has become a useful method in the followup of SCT patients.…”

Listeriosis in recipients of allogeneic blood and marrow transplantation: thirteen year review of disease characteristics, treatment outcomes and a new association with human cytomegalovirus infection

“…3,20 In our group, no deaths were attributed to listeriosis, which was in concert with observations reported by Long et al 21 Reactivation of a latent Herpesviridae infection following allogeneic transplantation has been recognized as a common cause of serious morbidity and death. 5,6,10,11,19 High-grade HCMV viremia is associated with marked suppression in T lymphocyte functions. [7][8][9] We suspect, that HCMV-induced dysfunction of innate immunity including natural killer cells and impaired handling of intracellular pathogens by the tissue macrophages due to sub-optimal priming by Th-1 cytokines may have contributed to the evasion of primary and secondary host defenses against L. monocytogenes in our transplant recipients.…”

“…[2][3][4] Reactivation of human cytomegalovirus (HCMV), on the other hand, is not uncommon in patients undergoing allogeneic blood, marrow or organ transplants and is associated with a marked increase in short-term morbidity and mortality. 5,6 Reactivation of HCMV is associated with impairment of T lymphocyte recovery due to virus-related marrow aplasia, and graft failure. 7 Virus mediated suppression of T lymphocyte-dependent immune responses, which include delayed regeneration of certain lymphocyte subsets, up-regulation of Th-2 cytokines, suppression of interferon-gamma, interleukin-2 (IL-2) secretion and hyporesponsiveness of CD3 + receptormediated T cell activation may increase the risk of secondary opportunistic infections.…”