Myeloblastoma formation in acute myeloid leukemia

Iizuka, Yoshikazu; Aiso, Masumi; Oshimi, Kazuo; Kanemaru, Mineo; Kawamura, Masaaki; Jin, Tao; Horikoshi, Akira; Ohshima, Toshiteru; Mizoguchi, Hideaki; Horie, Takashi

doi:10.1016/0145-2126(92)90017-2

Cited by 59 publications

(43 citation statements)

References 19 publications

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“…28 This antigen has been associated with extramedullary disease, megakaryocytic differentiation, and a poor outcome in certain subtypes of AML. [29][30][31][32] Recently, 2 groups have reported that CD56 expression is associated with the S isoform of the PML-RAR␣ fusion transcript and a poor outcome. 33,34 Unfortunately, CD56 expression was not studied in the current analysis.…”

Section: Discussionmentioning

confidence: 99%

All-trans retinoic acid in acute promyelocytic leukemia: long-term outcome and prognostic factor analysis from the North American Intergroup protocol

Tallman

Andersen

Schiffer

et al. 2002

Blood

418

267

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We previously reported a benefit for alltrans retinoic acid (ATRA) in both induction and maintenance therapy in patients with acute promyelocytic leukemia (APL). To determine the durability of this benefit and identify important prognostic factors, long-term follow-up of the North American Intergroup APL trial is reported. A total of 350 patients with newly diagnosed APL were randomized to either daunorubicin and cytarabine (DA) or ATRA for induction and then either ATRA maintenance or observation following consolidation chemotherapy. The complete remission (CR) rates were not significantly different between the ATRA and DA groups (70% and 73%, respectively). However, the 5-year disease-free survival (DFS) and overall survival (OS) were longer with ATRA than with DA for induction (69% vs 29% and 69% vs 45%, respectively). Based on both induction and maintenance randomizations, the 5-year DFS was 16% for patients randomized to DA and observation, 47% for DA and ATRA, 55% for ATRA and observation, and 74% for ATRA and ATRA. There was no advantage of either induction regimen among any subgroups when CR alone was con-

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Section: Discussionmentioning

confidence: 99%

All-trans retinoic acid in acute promyelocytic leukemia: long-term outcome and prognostic factor analysis from the North American Intergroup protocol

Tallman

Andersen

Schiffer

et al. 2002

Blood

418

267

View full text Add to dashboard Cite

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“…Such variation in its site of occurrence complicates accurate diagnosis of GS, and, moreover, the low incidence of GS has impeded establishment of the clinical characteristics of patients with GS. Several studies have reported that specific factors, including French-American-British (FAB) M4 and M5 classification (11,12) and the expression of CD56 (13,14) or T-cell antigens (CD2, CD4 and CD7) (15,16) on leukemia cells, are associated with GS, while others have identified an association between GS and t(8;21) (17,18) or inv (16). (19,20) Establishment of the clinical characteristics of GS has been further impeded by the mixed results obtained by several studies that investigated the prognosis of GS in limited subpopulations of AML patients.…”

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confidence: 99%

Clinical significance of granulocytic sarcoma in adult patients with acute myeloid leukemia

et al. 2012

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To investigate the clinical significance of granulocytic sarcoma (GS) in adults with acute myeloid leukemia (AML), 434 consecutive patients with AML were analyzed retrospectively. Forty-five patients (10.4%) with GS at diagnosis were younger (P < 0.001), presented with higher white blood cell counts (P = 0.03) and were more likely to conform to French-American-British M4 (P = 0.001) and M5 (P = 0.045) classifications than those without GS. In contrast, no significant difference in frequency of cytogenetic abnormalities was found between the GS and non-GS groups. Treatment outcomes in 260 patients (40 with GS) who underwent intensive chemotherapy, excluding patients with acute promyelocytic leukemia, were investigated. Complete remission rates did not differ significantly between the GS and non-GS groups (75.0% vs 79.1%; P = 0.192, respectively) or the 5-year overall survival (OS) rates (39.9% vs 38.7%; P = 0.749, respectively). However, the GS group had a significantly higher relapse rate than the non-GS group (74.2% vs 55.3%; P = 0.048) and a significantly lower 5-year disease-free survival rate (8.2% vs 25.7%, respectively; P = 0.005). When considered together with the results of multivariate analysis, which identified the presence of GS as an independent predictor for disease-free survival time, these findings indicate that GS might identify a high-risk subset of patients with AML. (Cancer Sci 2012; 103: 1513-1517 G ranulocytic sarcoma (GS), a rare extramedullary tumor composed of malignant granulocytic precursor cells that affects 3-9% of patients diagnosed with acute myeloid leukemia (AML), (1)(2)(3) occurs concomitantly with or after a diagnosis of AML. Granulocytic sarcoma can occur in any organ and common sites are bones, lymph nodes, soft tissues and skin. (4) Other organs, including the brain, (5,6) orbit (7,8) and genitourinary system, (9,10) are infrequently affected by GS. Such variation in its site of occurrence complicates accurate diagnosis of GS, and, moreover, the low incidence of GS has impeded establishment of the clinical characteristics of patients with GS. Several studies have reported that specific factors, including French-American-British (FAB) M4 and M5 classification (11,12) and the expression of CD56 (13,14) or T-cell antigens (CD2, CD4 and CD7) (15,16) on leukemia cells, are associated with GS, while others have identified an association between GS and t(8;21) (17,18) or inv(16). (19,20) Establishment of the clinical characteristics of GS has been further impeded by the mixed results obtained by several studies that investigated the prognosis of GS in limited subpopulations of AML patients. Byrd et al. (21) found that GS was associated with unfavorable outcomes and a shorter survival time (median 5.4 months with GS vs 59.5 months without GS) among AML patients carrying t(8;21), whereas Felice et al. (22) argued that GS had no adverse prognostic impact on AML patients carrying t(8;21). In light of these discrepant findings, this study aimed to clarify the clinical significance of GS...

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“…unlike alveolar macrophages and interstitial mucosal mononuclear cells, leukocytes in the CNS show complete donor typing in the early phase when complete donor type hematopoiesis is observed; 12 (2) although leukocytes in the CSF are minimal, and turnover is very slow under normal conditions, they increase after TBI because of damage to the blood-brain barrier. 13,14 These previous reports may help to confirm the existence of a GVL effect in the CNS.…”

Section: Discussionmentioning

confidence: 99%

“…Some AML patients, particularly those with CD56-positive cells, develop GS in the brain. 2 Although a treatment approach for GS has not been fully established, it has been shown that local treatments such as radiotherapy and intrathecal therapy are ineffective even when there is no evidence of bone marrow disease. 3 The main reason for this is that most patients suffer a bone mar- row relapse after local therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Some patients, however, do experience a greater incidence of GS, including AML M2 with t(8;21)(q22;q22), 1 and AML with CD56-positive leukemia cells. 2 In many cases, GS appears adjacent to the bony or neural structures, and it can develop either before or after the onset of leukemia, and at any time during the clinical course. 4,5 Meningeal leukemia is common while intracerebral GS is rare.…”

Section: Discussionmentioning

confidence: 99%

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Three AML patients with existing or pre-existing intracerebral granulocytic sarcomas who were successfully treated with allogeneic bone marrow transplantations

Takada

Ito

Sakura

et al. 1999

Bone Marrow Transplant

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Summary:We report three acute myelogenous leukemia (AML) patients who developed intracerebral granulocytic sarcomas (GS) and were successfully treated with allogeneic BMT (allo-BMT). The diagnosis of one patient was AML M2 with myelofibrosis, and the other two patients were AML M4 with eosinophilia (AML M4 Eo), according to the FAB classification. Two patients first experienced a relapse in the brain that resulted in the formation of GS, followed by a relapse in the bone marrow. The remaining patient developed an optic nerve GS after suffering a bone marrow relapse. All three patients received irradiation for the GS and systemic chemotherapy before the allo-BMT. TBI was used for conditioning, and GVHD prophylaxis was with cyclosporine (CsA) and short-term MTX in all three cases. These patients are currently 9 to 37 months post-BMT without relapse. Thus, our experience suggests that allo-BMT is an effective treatment for AML patients with existing or pre-existing intracerebral GS. Keywords: AML; intracerebral granulocytic sarcoma; allogeneic BMT Granulocytic sarcoma (GS) is a rare extramedullary tumor composed of myeloblasts and other granulocytic precursors. The subgroups of AML, AML M2 with t(8;21)(q22;q22) 1 and AML with CD56-positive leukemic cells 2 tend to develop GS. Granulocytic sarcoma can occur at any location in the body in patients with adult AML, but it rarely does in the CNS. 3 Although such patients receive intracerebral treatment, whole brain irradiation, and/or systemic chemotherapy, they have low complete remission (CR) rates and short overall survivals. Hence, in some cases, aggressive therapy such as bone marrow transplantation is recommended. This report documents three AML patients with existing or pre-existing intracerebral GS who were successfully treated with allo-BMT. Case reports Case 1A 46-year-old male was diagnosed with AML M2, with myelofibrosis. At diagnosis, cytogenetic analysis showed 46, XY, 9q−. Flow cytometric analysis was compatible with AML, but CD56 was not examined. He achieved CR with enocitabine (BHAC) 2200 mg/m 2 i.v., daunorubicin (DNR) 240 mg/m 2 i.v. and mercaptopurine (6-MP) 700 mg/m 2 p.o. (total dose). Eleven months later, however, he complained of nausea, vomiting, and headache. A brain CT revealed the presence of enhanced multiple mass lesions. There was no indication of a bone marrow relapse, and a brain biopsy was not performed. A CNS relapse was diagnosed resulting in the formation of GS, and whole brain irradiation was given to 40 Gy. A brain CT subsequently detected no mass lesion. Notwithstanding, this patient suffered a bone marrow relapse 6 months later. He then received induction therapy with mitoxantrone (MIT) 30 mg/m 2 i.v., cytosine arabinoside (ara-C) 700 mg/m 2 i.v. and etoposide (VP-16) 560 mg/m 2 i.v., and the myeloblasts decreased to 7% of the bone marrow nucleated cells. Following this chemotherapy, he complained of a gait disturbance, and a brain MRI revealed mass lesions in the right frontal and left occipital lobes. Whole brain irradiation (...

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Myeloblastoma formation in acute myeloid leukemia

Cited by 59 publications

References 19 publications

All-trans retinoic acid in acute promyelocytic leukemia: long-term outcome and prognostic factor analysis from the North American Intergroup protocol

All-trans retinoic acid in acute promyelocytic leukemia: long-term outcome and prognostic factor analysis from the North American Intergroup protocol

Clinical significance of granulocytic sarcoma in adult patients with acute myeloid leukemia

Three AML patients with existing or pre-existing intracerebral granulocytic sarcomas who were successfully treated with allogeneic bone marrow transplantations

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