Graft-versus-leukemia effects in T lineage and B lineage acute lymphoblastic leukemia

Abstract

Summary:Allogeneic bone marrow transplantation is an effective treatment for acute lymphoblastic leukemia (ALL). 1 This efficacy is, in part, mediated by graft-versus-leukemia T and B lineage ALL cells express different levels of HLA-class II antigens, which may serve as targets for effects (GVL). 2,3 GVL is greatest in patients with acute or chronic graft-versus-host disease (GVHD). T cells are graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL). The object of this study was to determine important in GVHD; 4 removing T cells from donor bone marrow greatly reduces the incidence and severity of whether GVL effects after HLA-identical sibling bone marrow transplantation differed in T and B lineage GVHD but increases the relapse risk. Different leukemias respond differently to GVL. The rea-ALL. We studied 1132 patients with ALL of T lineage (n = 416) or of B lineage (cALLa + ) (n = 716) transson for this is uncertain. Molecules on the surface of leukemia cells may determine susceptibility to GVL. 6 In experiplanted in first (n = 605) or second (n = 527) remission with bone marrow from an HLA-identical sibling mental models, major histocompatibility complex (MHC) class I expression is needed for a CD8 + T lymphocyte donor, between 1982 and 1992, and reported to the IBMTR by 165 teams. Cox proportional hazards response whereas MHC class II is required for both initiating the immune response and serving as a target for cytoregression models were used to determine the relative risk (RR) of relapse in patients with acute (grades IItoxic CD4 + T lymphocytes. [7][8][9][10][11] Experimental data suggest that alloreactive CD4 + lymphocytes are able to kill leuke-IV) or chronic GVHD vs patients without GVHD. Acute and chronic GVHD were considered as time-dependent mia cells. 12,13 In ALL, class II antigen expression (HLA-DR) differs significantly among leukemia phenotypes; it is covariates. Patients transplanted in first and second remission were analyzed separately. GVHD decreased highest in B lineage ALL and less or absent in T lineage ALL. [14][15][16][17][18] It is thus plausible that the antileukemia effect relapse risks to a similar extent in T and B lineage ALL. For first remission transplants, relative risks of relapse of GVHD might occur preferentially in the HLA class IIbearing B lineage leukemias. The object of this study was for patients with vs those without GVHD was 0.34 for T lineage ALL and 0.44 for B lineage ALL. Correspondto address this question by comparing the effects of GVHD on relapse rates in B lineage and T lineage ALL. ing relative risks in second remission transplants were 0.54 and 0.61. This study confirms earlier findings of an antileukemia effect of GVHD in ALL. This effect was similar in T lineage and B lineage ALL, despite probMaterials and methods able differences in HLA-class II antigen expression. Keywords: ALL; bone marrow transplantation; graftPatients versus-leukemia; T lineage; B lineage Between 1982Between and 1992Between , 1955

Allogeneic SCT in refractory or relapsed adult ALL is effective without prior reinduction chemotherapy

“…15 Furthermore, the high OS rate of patients transplanted with active disease and no reinduction attempt may be due to the high incidence of extensive cGHVD in this subgroup (75 vs 39% in the reinduction group), which possibly correlates with a more potent GVL effect. 38,39 Whether this increased incidence of cGHVD has a biological explanation or whether it is due to statistical effects is difficult to say as we have not found a difference in conditioning regimen, donor type, stem cell source or use of prophylactic DLIs between the two groups. Kaplan-Meyer survival analysis suggested that the development of cGVHD leads to significantly better OS.…”

Preemptive alloimmune intervention in high-risk pediatric acute lymphoblastic leukemia patients guided by minimal residual disease level before stem cell transplantation

“…In 2 out of 16 patients, the leukemia relapsed very rapidly within 12 weeks although post-SCT MRD levels in blood and bone marrow became negative (that is, o1 Â 10 À4 ) immediately after SCT. In 8 out of the 14 remaining patients, a bone marrow and/or a blood sample with a high MRD level (X1 Â 10 À4 ) preceded the clinical relapse by 9 weeks (median, range 0-30) and 8 weeks (median, range [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], respectively. The slightly earlier detection in bone marrow occurred despite more frequent sampling of blood than of bone marrow.…”

“…[10][11][12][13] The occurrence of graft versus host disease (GvHD) and reduction of immunosuppressive medication shortly after SCT has been reported to correlate with protection against relapse of ALL albeit less strongly than for other, especially myeloid type, hematological malignancies. 10,[14][15][16] The administration of donor lymphocyte infusion (DLI) at the time of overt relapsing ALL was usually not effective.…”

Evidence for a GVL effect following reduced-intensity allo-SCT in ALL: a British Society of Blood and Marrow Transplantation study

“…6 There is evidence for a GVL effect in ALL; GVHD is associated with lower RI and allo-SCT provides significant benefit over autologous transplant. 3,7,8 A reduced intensity conditioning (RIC) approach may reduce RI and lower TRM, extending applicability to older patients and those with comorbidities. Several retrospective studies have examined RIC allo-SCT for ALL.…”