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...
The risk of locoregional recurrence in resected gastric adenocarcinoma is high, but the benefit of adjuvant treatment remains controversial. In particular, after extended lymph node dissection, the role of radiotherapy is questionable. Since 1995, we started a clinical protocol of adjuvant chemoradiotherapy after D2 gastrectomy and analysed the patterns of failure for 291 patients. Adjuvant chemotherapy consisted of five cycles of fluorouracil and leucovorin, and concurrent radiotherapy was given with 4500 cGy from the second cycle of chemotherapy. With a median follow-up of 48 months, 114 patients (39%) showed any type of failure, and the local and regional failures were seen in 7% (20 out of 291) and 12% (35 out of 291), respectively. When the recurrent site was analysed with respect to the radiation field, in-field recurrence was 16% and represented 35% of all recurrences. Our results suggest that adjuvant chemoradiotherapy has a potential effect on reducing locoregional recurrence. Moreover, low locoregional recurrence rates could give a clue as to which subset of patients could be helped by radiotherapy after D2 gastrectomy. However, in order to draw a conclusion on the role of adjuvant radiotherapy, a randomised study is needed. Gastric cancer is the most common cancer in Korea (Shin et al, 2002). Complete tumour removal with sufficient resection margin plus extended lymph node dissection is considered to be the most important factor in terms of reduced locoregional recurrence and improved survival. Although the incidence of early gastric cancer is increasing, most patients still present with an advanced stage, and, even after complete resection, 38 -94% of patients developed locoregional recurrence (McNeer et al, 1951;Gunderson and Sosin, 1982;Wisbeck et al, 1986;Landry et al, 1990), which translates into 33 -69% of all recurrences (Gunderson and Sosin, 1982;Landry et al, 1990;Maehara et al, 2000;Yoo et al, 2000). However, high recurrence rates may be reduced by adjuvant treatment, so postoperative adjuvant radiotherapy and/or chemotherapy is generally performed.There were several studies (GITSG, 1982;Moertel et al, 1984;Allum et al, 1989;Regine and Mohiuddin, 1992) showing positive effects of radiotherapy and/or chemotherapy in patients with locally advanced or unresectable gastric adenocarcinoma, but the benefit of adjuvant treatment after curative resection remains controversial. Intergroup trial (MacDonald et al, 2001) showed that adjuvant chemoradiotherapy reduced recurrences and increased survival of patients with gastric adenocarcinoma. However, after extended lymph node dissection with R0 gastrectomy, there are no data regarding whether adjuvant radiotherapy could reduce locoregional recurrence and increase survival.The purpose of this study was to analyse the patterns of failure in patients with gastric adenocarcinoma after gastrectomy with D2 lymph node dissection plus postoperative chemoradiotherapy, and to evaluate any effect of adjuvant radiotherapy on locoregional recurrence reduction and su...
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