Summary:While allogeneic stem cell transplantation (SCT) is curative for a significant number of patients with AML, relapse of disease within the bone marrow and/or extramedullary (EM) sites following high-dose therapy continues to limit the success of this treatment. Between October 1985 and December 1996, 81 adults underwent allogeneic SCT for de novo AML at our centre. Fortytwo patients remain alive and free of leukaemia with a median follow-up of 50 months. The 5-year actuarial event-free survivals (EFS) for all patients and for those undergoing SCT in CR1 or with advanced disease were 46% (95% confidence interval (CI) 34-58%), 63% (CI 46-76%), and 19% (CI 7-36%), respectively. Twentytwo patients relapsed at a median of 8 (range 1.6-54.5) months with the actuarial risk of relapse for all, CR1 and advanced disease patients being 38%, (CI 27-52%), 23% (CI 13-40%) and 68% (CI 46-88%), respectively. Ten patients relapsed at EM sites; six of these (27% of relapses) had an isolated EM relapse at a median of 31 (range 8.5-54) months. Three of the patients with isolated EM relapse survived у24 months following relapse and two patients remain disease-free at 29+ and 33+ months. BuCy conditioning followed by allogeneic SCT in AML results in satisfactory EFS although there is a significant risk of late isolated EM relapse. Keywords: acute myelogenous leukemia; extramedullary relapse; allogeneic BMT Allogeneic stem cell transplantation (SCT) is an effective therapy for patients with AML. 1-3 Long-term event-free survival (EFS) can be achieved in approximately 60% of patients undergoing SCT in first complete remission (CR1) 4-9 and 25-30% of those with more advanced disease. 1,2,4,10,11 However, there remains some controversy regarding the optimal transplant preparative regimen in AML. For patients transplanted in CR1, one randomized study demonstrated a regimen employing TBI to be superior to busulfan/cyclophosphamide (BuCy) conditioning, 7 while another showed the regimens to be equivalent. 8 One of the contributing factors to an unsuccessful result with SCT regardless of the preparative regimen utilized is relapse, occurring in 20-25% and 30-50% of AML patients transplanted during CR1 or with advanced disease, respectively. 1,2,4,7,9 The site of relapse after a TBI-based preparative regimen is usually the marrow with or without extramedullary (EM) disease. 12 Isolated EM relapse occurred in only 13% of patients developing recurrent disease after TBI conditioning in one study. 12 Little is known about the risk of isolated EM relapse of AML following BuCy with a small number of such patients reported recently in a survey by the European Group for Blood and Marrow Transplantation (EBMT) of more than 3000 AML transplants. 13 The present review was prompted by the observation that several patients receiving allogeneic SCT after BuCy at our institution experienced isolated EM relapse.
Summary:analysis of the marrow revealed trisomy 8 and t(15;17) ( Table 1). He was treated with Ara-C and amsacrine and a second remission was achieved after two courses. FollowAfter treatment of acute leukemia (typically ALL and the monocytic variants of AML), relapse may occur at up marrow cytogenetic analysis was normal. This hospitalization was complicated by Aspergillus flavus pneumonia sites other than the marrow. Isolated extramedullary relapse of acute promyelocytic leukemia (APL) howrequiring ICU admission and treatment with 3000 mg of amphotericin B. He was eventually discharged home on cisever, is rare. We describe such an event in a man who underwent allogeneic BMT for APL in second relapse retinoic acid in October 1985.Because of concern about Aspergillus reactivation, an and 4 years later presented with testicular relapse. The marrow was morphologically and cytogenetically norallogeneic BMT was considered inappropriate at this time.He remained well on cis-retinoic acid until December 1987 mal, but RT-PCR analysis revealed the specific PML/RAR chimeric RNA transcript.when he developed hemoptysis. Bronchoscopy was performed and later right upper lobectomy for presumed AsperKeywords: testicular relapse; acute promyelocytic leukemia; allogeneic BMT gillus infection. The pathology of the resected lung, however, revealed necrotizing granulomas consistent with active pulmonary tuberculosis. He was therefore treated with an 8-month course of anti-tuberculous medication. Acute promyelocytic leukemia (APL) is a distinct subtype Treatment with cis-retinoic acid continued. of AML characterized by a consumptive coagulopathy, a Second relapse occurred in September 1990. Cytogenetic specific chromosomal rearrangement, a defined molecular analysis of the marrow revealed tetrasomy 8 and t(15;17) abnormality in a retinoid receptor, and a relatively good (Table 1). He was treated with Ara-C and DNR but a folprognosis. The (15;17) chromosomal translocation fuses the low-up marrow revealed persistent disease. In October PML gene on chromosome 15 with the RAR gene on chro-1990, he underwent an HLA-matched sibling donor BMT mosome 17, resulting in a hybrid gene PML/RAR which using BU, CY conditioning and CsA with methylprednisoencodes a fusion protein, undoubtedly involved in leukelone as GVHD prophylaxis. His hospital course was relamogenesis. 1 Both combination chemotherapy 2 and all-trans retinoic acid (ATRA) 3 are effective treatments.We describe an unusual case in which isolated testicular Table 1 Karyotype of marrow cells at various time points from relapse of APL occurred after allogeneic BMT. 1984-1994 Marrow karyotypeCase report Diagnosis (March 1984) Failed analysisA 34-year-old East Indian man presented in March 1984First relapse (August 1985) 47, XY, +8, t(15;17) [10] with APL. Remission was achieved with high-dose Ara-C Second remission (September 1985) 46, XY [25] and DNR, and consolidated with the same drugs.
Using strict FAB criteria, 39 cases of monocytic leukemia were identified in 463 consecutive cases of AML. Patients had a median age of 49 with no sex predominance. Extramedullary disease and hyperleukocytosis were common (54% and 36% of patients respectively). Cytogenetic analysis was successful in 38 of 39 patients; 71% had a cytogenetic abnormality and 42% of these involved chromosome 11; 14 of 16 chromosome 11 abnormalities involved the region of 11q23. Non-chromosome 11 abnormalities tended to occur in older patients and to be associated with a lower platelet count; patients with the translocation 9;11 tended to have a lower white count and a higher incidence of therapy-related leukemia. 35 patients were treated with induction therapy including intensive chemotherapy (n = 33) and allogeneic BMT at presentation (n = 2). Patients who entered remission underwent consolidation chemotherapy, autologous BMT, or allogeneic BMT depending on policies at the time of diagnosis. Of 6 patients who underwent further intensive chemotherapy there is 1 long-term disease-free survivor. 3 of 8 patients undergoing autologous BMT and 2 of 3 patients undergoing allogeneic BMT are long-term disease-free survivors. We conclude that this specific subtype of AML, relatively rare when strict criteria are applied, is associated with unique biologic and clinical features and that the high relapse rate associated with conventional therapy makes new treatment approaches involving stem cell transplantation or immunomodulation necessary.
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