Laboratory Correlates and Prognostic Significance of Granular Acute Lymphoblastic Leukemia in Children: A Pediatric Oncology Group Study

Cerezo, Lizardo; Shuster, Jonathan J.; Pullen, D. Jeannette; Brock, Brenda; Borowitz, Michael J.; Falletta, John M.; Crist, William M.; Head, David R.

doi:10.1093/ajcp/95.4.526

Cited by 31 publications

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“…Also, granules had a greater effect than L2 on event-free survival. Involvement of CNS at diagnosis was not reported by Cerezo et al 15 Both of our patients had CNS disease at diagnosis. It will be interesting to see in larger studies if there is an association between granular ALL and CNS involvement at diagnosis.…”

Section: Discussionsupporting

confidence: 47%

“…The largest group of granular ALL cases was reported by Cerezo et al, 15 who described 56 cases of granular ALL in a review of 1252 children with ALL. Cases were classified as granular ALL if they met the FAB morphologic criteria for ALL and were characterized by the presence of more than 5% marrow blasts, with at least three clearly defined azurophilic cytoplasmic granules.…”

Section: Discussionmentioning

confidence: 99%

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Granular Acute Lymphoblastic Leukemia: Report of Two Cases and Review of the Literature

et al. 1996

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The classification of acute leukemias into lymphoid leukemia (ALL) and nonlymphoid leukemia (ANLL) is of critical therapeutic importance. The differentiation of ALL from ANLL is usually achieved through morphologic, cytochemical and immunophenotypic analysis of leukemic blasts. One of the main morphologic criteria in the differentiation between the two types is the presence of granules in the cytoplasm of ANLL blasts. There have been scattered reports of patients with ALL who have lymphoblasts with azurophilic cytoplasmic granules. We describe two cases of granular ALL with review of the literature. Case Report Case 1A 22-year-old Saudi male was referred to King Khalid University Hospital (KKUH) in April 1995 with a diagnosis of ALL. He presented with malaise and shortness of breath for one month prior to admission. On examination, he was pale with no jaundice or cyanosis. He had generalized lymphadenopathy and hepatosplenomegaly. Chest and central nervous system (CNS) examinations were unremarkable. The diagnosis of ALL was confirmed (see below) and chemotherapy was started using hydroxyurea 2 g, p.o., q.i.d., for three days, followed by mitoxantrone 12 mg/m 2 intravenously (IV) daily for three days, vincristine 1.4 mg/m 2 IV weekly for seven weeks, and methylprednisolone 60 mg/m 2 IV daily for 21 days. Because of CNS involvement, he was started on intrathecal (IT) methotrexate (MTX) 10 mg, cytosine arabinoside (Ara-C) 50 mg and hydrocortisone 50 mg three times a week for a total of 10 doses. Induction was complicated by fever and neutropenia and he was managed with broad spectrum antibiotics and amphotericin-B. He did not achieve complete remission. Reinduction was started, but the patient died of neutropenia and septic shock. Hematological EvaluationOn admission, complete blood count (CBC) revealed a white blood count (WBC) of 23.8xl0 9 /L, hemoglobin (Hb) of 107 g/L, and platelet count of 59xl0 9 /L. The WBC differential count showed 8% neutrophils, 70% lymphocytes and 20% blasts. Bone marrow (BM) aspirate revealed hypercellular marrow with 55% blasts. The blasts were variable in size with some showing high nuclear cytoplasmic (N/C) ratio, while others were larger with low N/C ratio and prominent nucleoli. The morphology was that of L2 by the French American British (FAB) classification of ALL.1 Fifteen percent of the blasts contained cytoplasmic granules that were variable in size and stained purple by May-Giemsa stain. The number of granules was also variable, but most of the blasts contained more than three granules. Occasional hand mirror cells were also present. Auer rods were absent.The blasts were negative for Sudan black (SBB) and chloroacetate esterase (CAE) and positive for periodic acid Schiff (PAS), nonspecific esterase (NSE) without inhibition by sodium fluoride (NaFl), and weakly positive for acid phosphatase (AP). Flow cytometry was performed on the bone marrow aspirate and showed the blasts to be positive for CD10 (CALLA), CD19, CD20, CD22 and HLADR and negative for CD7, CD3, CD13 and CD33. T...

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Section: Discussionsupporting

confidence: 47%

Section: Discussionmentioning

confidence: 99%

Granular Acute Lymphoblastic Leukemia: Report of Two Cases and Review of the Literature

et al. 1996

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“…The frequency of cases showing granules was higher than the rates of granular ALL published by others (>5% of the blasts showing at least three clearly defined fairly large azurophilic granules) (Smith & Collins, 1990;Cerezo et al, 1991;Takemori et al, 1992;Schwarzinger et al, 1993). In a large study by the Pediatric Oncology Group, granular ALL accounted for 4·5% of 2096 cases of ALL (Cerezo et al, 1984), others have reported a frequency of 7% in children (Darbyshire et al, 1987).…”

Section: Discussionmentioning

confidence: 58%

“…, granules (Cantù -Rajnoldi et al, 1989;Smith & Collins, 1990;Cerezo et al, 1991;Grogan et al, 1981;Darbyshire et al, 1987;Hay et al, 1987;Fradera et al, 1986), markedly hyperchromatic convoluted nuclei (McKenna et al, 1979;Kernan et al, 1986), radial segmentation of nuclei (Neftel et al, 1983), or hand-mirror appearance of the blasts (Glassy et al, 1980;Gramatzki et al, 1985;Cerezo et al, 1984). This paper presents a detailed morphological and cytochemical analysis of 150 consecutive cases of T-lineage ALL diagnosed by the central diagnostic review panel of the German Multicentre ALL Study Group (GMALL).…”

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confidence: 99%

Morphological and cytochemical findings in 150 cases of T‐lineage acute lymphoblastic leukaemia in adults

et al. 1997

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Summary.We evaluated the morphological findings in 150 consecutive cases of T-lineage acute lymphocytic leukaemia (T-ALL). Cytochemistry including PAS staining and acid phosphatase reaction proved of limited value for the diagnosis of ALL.The diagnosis of acute leukaemia was easy to establish in most instances. However, in a few cases the leukaemic cells were difficult to recognize as blasts. The nuclei of such cells showed condensed chromatin and nucleoli were lacking, and was encountered particularly in thymic ALL.Basophilic cytoplasm combined with prominent vacuolization suggestive of mature B-ALL (ALL-L3 type), was observed in 16 cases. Other features, however, such as cell size, polymorphism, chromatin structure, sparse cytoplasm or focal positivity for acid phosphatase, excluded a diagnosis of ALL-L3 in those cases.Distinction from hybrid leukaemia was difficult in 20 cases, because of a low percentage of peroxidase-positive blasts or other features which suggested a separate myeloid leukaemia component. In nine of these the hybrid nature of the leukaemia was considered as certain on the basis of morphology. Seven cases had been diagnosed as biphenotypic with coexpression of myeloid and lymphoid markers by immunological techniques.In conclusion, our analysis showed some serious pitfalls of the morphology in T-ALL, clearly indicating the need for immunological analysis of the leukaemic cells. However, morphology remains an essential component of the diagnostic repertoire, especially when the marrow is difficult to aspirate and in cases with equivocal immunological findings. Furthermore, recognition of a separate myeloid leukaemic component in addition to the lymphatic one requires a morphological analysis.

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“…Azurophilic cytoplasmic granules in blasts, usually a feature of acute myeloid leukemia (AML), may uncommonly be seen in acute lymphoblastic leukemia (ALL) [3,7,12]. Another unusual accompaniment of ALL is hypereosinophilic syndrome (HES) [2].…”

Section: Introductionmentioning

confidence: 99%

Granular acute lymphoblastic leukemia with hypereosinophilic syndrome

Jain

Kumar

Gujral

et al. 2000

Annals of Hematology

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A four-year-old boy presented with marked peripheral blood eosinophilia (absolute eosinophil count of 54 x 10(9)/1), features of hypereosinophilic syndrome, and acute lymphoblastic leukemia (ALL-L2), the latter characterized by the presence of granular blasts. Blasts were negative for myeloperoxidase, non-specific esterase, acid phosphatase, periodic-acid Schiff stain, and toluidine blue. They exhibited an early pre-B immunophenotype (TdT, CD19, CD10, CD20 and CD22 positive) and stained negative for T (CD7, CD2, CD5 and CD3) and myeloid markers (MPO, CD33 and CD13). Chromosomal analysis revealed a normal karyotype. To the best of our knowledge, this case represents the first report of the coexistence of granular ALL and hypereosinophilic syndrome.

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Laboratory Correlates and Prognostic Significance of Granular Acute Lymphoblastic Leukemia in Children: A Pediatric Oncology Group Study

Cited by 31 publications

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Granular Acute Lymphoblastic Leukemia: Report of Two Cases and Review of the Literature

Granular Acute Lymphoblastic Leukemia: Report of Two Cases and Review of the Literature

Morphological and cytochemical findings in 150 cases of T‐lineage acute lymphoblastic leukaemia in adults

Granular acute lymphoblastic leukemia with hypereosinophilic syndrome

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