Summary:A total of 118 consecutive adult patients with acute leukemia (78 AML, 36 ALL, and four acute mixed lineage leukemia) underwent allogeneic hematopoietic cell transplantation (HCT) after conditioning with BuCy (n ¼ 113) or a nonmyeloablative regimen of busulfanfludarabine (n ¼ 5). After a median follow-up of 35.8 months (range, 6.4-91.0), 34 patients experienced at least one episode of leukemia relapse. Of 34 initial episodes, 14 (41%) occurred in extramedullary sites, with (n ¼ 8) or without (n ¼ 6) concomitant bone marrow involvement. The median time to relapse in the extramedullary sites was longer than that of relapse in bone marrow only (13.5 vs 6.1 months, P ¼ 0.046). Acute leukemia subtype and disease status at HCT showed an independent predictive value for overall relapse, as well as for extramedullary relapse with or without bone marrow involvement (Philadelphia chromosome positive acute leukemia vs low-risk AML, relative risk 22.68 (95% CI, 2.18-235.64); other than first CR vs first CR, relative risk 5.61 (95% CI, 1.80-17.51)), but not for bone marrow relapse. Our study suggests that there may be different pathogenetic mechanisms for bone marrow vs extramedullary relapse of acute leukemia after allogeneic HCT. The mode of relapse needs to be investigated in future reports of acute leukemia treated with allogeneic HCT. Bone Marrow Transplantation (2003) 32, 835-842. doi:10.1038/sj.bmt.1704223 Keywords: extramedullary relapse; acute leukemia; allogeneic HCT Allogeneic hematopoietic cell transplantation (HCT) is now considered part of a standard treatment modality for a significant subset of patients with acute leukemia. 1-3 The curative effect of allogeneic HCT is attributable to its ability to decrease leukemia relapse significantly when compared to conventional or high-dose chemotherapy including autologous HCT. This remarkable effect is due to the graft-versus-leukemia (GVL) effect that occurs after allogeneic HCT. Although the overall frequency of acute leukemia relapse is less after allogeneic HCT, a high proportion of extramedullary relapses 4-7 in extremely diverse sites has been reported, including the brain, [8][9][10][11] head and neck, [8][9][10]12 gastrointestinal tract, 13 breast, 14,15 liver, 9 pancreas, 16 urogenital tract, 13,17 spinal canal and paravertebral tissue, 8 bone and periosseous tissue, 13,14,18 pleura, 14 pericardium, 9 peritoneum, 19 and skin. 20 The median time from allogeneic HCT to acute leukemia relapse was longer in cases with extramedullary relapse with or without bone marrow involvement when compared to cases of bone marrow only relapse. [4][5][6] Uneven effectiveness of the GVL effect in the body of patients was suggested as one of the several possible mechanisms for the increased frequency and wide distribution of extramedullary relapse after allogeneic HCT. 4,6 However, other factors, such as nature of the leukemic blasts, status of acute leukemia at HCT, and conditioning regimen may also influence the frequency of extramedullary relapse.This study was undert...

Summary:Hematopoietic chimerism as a predictive marker for the relapse of acute leukemia after allogeneic BMT was evaluated in a prospective study. Monthly assays of hematopoietic chimerism were performed from peripheral blood samples by PCR amplification of short tandem repeats or amelogenin loci. Between December 1997 and June 1999, 33 patients enrolled and 30 were evaluable (two early deaths, one lack of informative bands for chimerism evaluation). There were 14 male and 16 female patients (15 AML and 15 ALL) with a median age of 31 years (range 16-46). Mixed chimerism (MC) was observed at least once in 14 of 30 patients (47%). There was no significant difference between 14 patients who showed MC (MC group) and 16 patients who did not show MC (complete chimerism (CC) group) in terms of age, sex, disease status at BMT, donor type, and the number of bone marrow cells infused. There was no significant difference in the neutrophil and platelet engraftment rates between the two groups. After a median follow up of 10.9 months (range 4.3-22.4), five patients in the CC group and two patients in the MC group relapsed (P = 0.27). All five patients who relapsed in the CC group maintained CC up to 1 month prior to clinical relapse. Our study demonstrated that the patients who showed MC post BMT did not have higher risk of relapse of acute leukemia when compared to patients who did not show MC. Sensitive PCR-based assays for hematopoietic chimerism applied on a monthly basis after allogeneic BMT could not predict relapse of acute leukemia. Bone Marrow Transplantation (2000) 26, 327-332. Keywords: acute leukemia; allogeneic bone marrow transplantation; mixed chimerism; relapse It is now well established that a certain proportion of patients who undergo myeloablative chemoradiotherapy and allogeneic bone marrow transplantation (BMT) show