Extramedullary acute promyelocytic leukemia

Wiernik, Peter H.; Bellis, Roberto De; Muxí, Pablo; Dutcher, Janice P.

doi:10.1002/(sici)1097-0142(19961215)78:12<2510::aid-cncr10>3.0.co;2-z

Cited by 86 publications

(51 citation statements)

References 25 publications

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“…31 None of the three AML-M3 patients in our study had exposure to ATRA prior to SCT, although one (UPN 537), as we previously reported, 32 had received extensive isotretinoin (13-cis retinoic acid) maintenance therapy before transplant. Notably, of the three AML-M3 EM relapse patients, one was of East Indian, one was of Asian, and one was of Northern European descent.…”

Section: Discussionmentioning

confidence: 69%

“…30 It is of particular interest that three patients with isolated post-SCT EM relapse had AML-M3, a disease that has rarely been reported to involve EM sites. 28,31 However, of the five published cases of isolated AML EM relapse following BuCy, including an earlier report from our centre, 13,32 three of the patients had AML-M3. It could be argued that the additional cytogenetic abnormalities in two of our three AML-M3 patients (tetrasomy 8 and three extra copies of chromosome 21, respectively), signified a more aggressive form of AML-M3 with a propensity for EM disease.…”

Section: Discussionmentioning

confidence: 84%

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High incidence of extramedullary relapse of AML after busulfan/cyclophosphamide conditioning and allogeneic stem cell transplantation

et al. 1998

Bone Marrow Transplant

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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.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 84%

High incidence of extramedullary relapse of AML after busulfan/cyclophosphamide conditioning and allogeneic stem cell transplantation

et al. 1998

Bone Marrow Transplant

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“…Less than 30 cases have been reported in the literature until now and the diagnosis in most of these cases was not confirmed by cytogenetic or molecular studies. 6,7,9 However, since the first report by Weiss and Warrell, 5 extramedullary relapses in APL patients receiving ATRA induction have been detected more frequently than before, 6,7,10 but the correlation between ATRA usage and the subsequent extramedullary disease remains obscure. In this retrospective study, it was demonstrated that patients receiving ATRA induction had an increased risk in extramedullary relapse compared with those with chemotherapy alone.…”

Section: Discussionmentioning

confidence: 99%

“…This event was rarely reported in those patients with cytogenectically and/or molecularly con- firmed APL who were treated with chemotherapy alone. [5][6][7] However, it is not yet clear whether ATRA truly increases the risk of extramedullary relapse and what are the risk factors. In this study, relapsed APL patients treated with or without ATRA were compared for the incidence of extramedullary involvement.…”

Section: Introductionmentioning

confidence: 99%

Extramedullary relapse after all-trans retinoic acid treatment in acute promyelocytic leukemia – the occurrence of retinoic acid syndrome is a risk factor

Tang

et al. 1999

Leukemia

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All-trans retinoic acid (ATRA) is now a standard agent for remission induction of acute promyelocytic leukemia (APL). Recently, extramedullary relapse, which was a rare condition in APL patients after chemotherapy alone, was reported with an increased frequency after ATRA treatment. However, it is not yet clear whether ATRA truly increases the risk of extramedullary recurrence and what are the risk factors. In this study, three of 13 patients with recurrent APL after prior treatment of ATRA were found to have extramedullary involvement, compared with none in 11 recurrent patients previously treated with chemotherapy alone (estimated relative risk 2.100, 95% confidence interval 1.341-3.289). Furthermore, in the former group of patients, the development of retinoic acid (RA) syndrome during prior induction treatment was significantly associated with extramedullary involvement at relapse (three in five patients with RA syndrome vs none in eight without the syndrome, estimated relative risk 5.000, 95% confidence interval 1.448-17.271). In conclusion, ATRA may predispose APL patients to extramedullary involvement at relapse and the occurrence of RA syndrome is a risk factor for it. Further studies are needed to confirm these findings. It also remains to be clarified whether treatment modification is necessary in patients who develop RA syndrome during ATRA treatment.

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“…6 It has been suggested that cutaneous cases of extramedullary disease in acute promyelocytic leukemia may have a characteristic predilection to occur at sites of puncture for blood and bone marrow samples and that treatment with ATRA may predispose these patients to extramedullary relapse. 7,8 We believe that fluorescence in situ hybridization (FISH) provides an efficient and reliable method of detecting the t(15;17) rearrangement associated with acute promyelocytic leukemia in suspected cases of leukemia cutis, and will aid in distinguishing cutaneous involvement by acute promyelocytic leukemia from reactive processes or other neoplastic processes that can occur in this setting.…”

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confidence: 99%

Fluorescence in situ hybridization investigation of cutaneous lesions in acute promyelocytic leukemia

et al. 2005

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Cutaneous manifestations of acute promyelocytic leukemia are rare but well documented. Skin biopsies of leukemia can be difficult to confirm using morphology alone, and paraffin section immunophenotyping is not specific in separating acute promyelocytic leukemia from other acute myeloid leukemias involving the skin or inflammatory conditions, such as Sweet's syndrome and all-trans retinoic acid-associated genital ulcers, which may mimic leukemia cutis. Fluorescence in situ hybridization has been shown to be a fast and effective method of detecting the PML/RARA fusion gene characteristic of acute promyelocytic leukemia in fresh blood and bone marrow samples. Fluorescence in situ hybridization has also been demonstrated to be effective in detecting other chromosomal rearrangements in paraffin-embedded tissue. This retrospective study of cutaneous lesions from four patients with acute promyelocytic leukemia evaluates the utility of performing fluorescence in situ hybridization to confirm the presence of cutaneous manifestations of acute promyelocytic leukemia in formalinfixed, paraffin-embedded skin biopsies. All patients had previous bone marrow findings of acute promyelocytic leukemia with characteristic morphology, immunophenotype, and cytogenetic studies, which detailed the presence of the t(15;17)(q22;q12) rearrangement. Two skin biopsies showed an infiltrate of blastic cells involving the dermis in a diffuse pattern and one biopsy had a perivascular/periadnexal pattern. The fourth case, involving the scrotum, showed a predominant neutrophilic infiltrate diffusely involving the dermis and epidermis with a subset of blastic cells. Nuclei were extracted from core biopsies of the formalin-fixed paraffinembedded tissue and fluorescence in situ hybridization was performed using a dual color, dual fusion PML/ RARA probe. All cases showed evidence of the t(15;17) rearrangement, with 90, 79, 51 and 16% positive signal patterns, each well above background limits. Fluorescence in situ hybridization appears to be a robust technique to detect cutaneous manifestations of acute promyelocytic leukemia in formalin-fixed paraffinembedded skin biopsies. Modern Pathology (2005) 18, 1569-1576.

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Extramedullary acute promyelocytic leukemia

Abstract: BACKGROUND. Extramedullary acute promyelocytic leukemia (APL) is rare, and said to be more common after treatment with all-trans retinoic acid (ATRA) than after any other treatment.

Cited by 86 publications

References 25 publications

High incidence of extramedullary relapse of AML after busulfan/cyclophosphamide conditioning and allogeneic stem cell transplantation

High incidence of extramedullary relapse of AML after busulfan/cyclophosphamide conditioning and allogeneic stem cell transplantation

Extramedullary relapse after all-trans retinoic acid treatment in acute promyelocytic leukemia – the occurrence of retinoic acid syndrome is a risk factor

Fluorescence in situ hybridization investigation of cutaneous lesions in acute promyelocytic leukemia

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