Bone marrow vs extramedullary relapse of acute leukemia after allogeneic hematopoietic cell transplantation: risk factors and clinical course

Abstract

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...

Treatment of relapsed acute myeloid leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF-primed donor leukocyte infusion: a high incidence of isolated extramedullary relapse

“…2,37,41,42 Although it should be interpreted cautiously, considering the limited number of patients in our study, our finding, that all the initial relapses after DLI occurred only at extramedullary sites, suggests that these isolated extramedullary relapses might occur more frequently after DLI than after BMT. Although the reason this uneven GVL effect between marrow and extramedullary sites tends to be stronger in the post-DLI than in the post-BMT setting remains unknown, it is possible that the patients enrolled in our study may represent a selected group.…”

Extramedullary relapses after allogeneic non-myeloablative stem cell transplantation in multiple myeloma patients do not negatively affect treatment outcome

“…This is not only reported for MM, but also for acute leukaemias. 15,16 These EM relapses are believed to indicate transformation of the disease, associated with a more aggressive behaviour, therapy resistance and short survival. However, reports regarding this subject in MM are lacking data on the efficacy of the relapse treatment or are case reports.…”

Idarubicin-intensified BUCY2 regimens may lower relapse rate and improve survival in patients undergoing allo-SCT for high-risk hematological malignancies: a retrospective analysis

“…Nevertheless, the relapse rate after such transplantation remains high, especially for the high-risk disease states, the relapse rate can reach up to 23-50%. [3][4][5] Different modified conditioning regimens, including intensive chemotherapeutic blocks, using promising new agents before transplantation, have been explored to achieve and sustain MRD negativity. Some nonrandomized studies on the use of an intensified conditioning have reported better disease control for high-risk patients, but higher rates of toxicity and TRM have also been reported.…”