Acute nonlymphocytic leukemia, preleukemia, and acute myeloproliferative syndrome secondary to treatment of other malignant diseases. Clinical and cytogenetic characteristics and results of in vitro culture of bone marrow and HLA typing

Pedersen‐Bjergaard, Jens; Philip, Preben; Mortensen, Børge Thing; Ersbøll, Jens; Jensen, Gunde Egeskov; Panduro, J.; Thomsen, Mögens

doi:10.1182/blood.v57.4.712.712

Cited by 168 publications

(24 citation statements)

References 36 publications

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“…The incidence of HAL in adult patients with acute leukemia in our study was 1 1-6 per cent and is in agreement with that reported in the literature of 7.7 per cent (3) 9.6 per cent (359, 10.7 per cent and 14.9 per cent (38). HAL may become more frequently recognized in the future because of (1) an increasing number of patients with treatment related acute and smoldering leukemias following treatment with cytotoxic chemotherapy alone or in combination with radiotherapy for a variety of malignant diseases (Saarni and Linman, 1973;Greenberg et al, 1976;Pedersen-Bjergaard et al, 1981;Rowley et al, 1981;Anderson et al, 1981), and (2) the increasing frequency of elderly patients being diagnosed as having various dysmyelopoietic syndromes evolving into leukemia (Saarni and Linman, 1973;Greenberg et al, 1976;Pedersen-Bjergaard et al, 1981;Rowley et al, 1981;Anderson et al, 1981, Greenberg, 1983Pierre, 1974). The indidence of hypocellular and normocellular marrows in myelodysplasic syndromes ranges from 8-1 0 per cent in myelodysplasia (44,45), 22-36 per cent in smoldering or subacute myelogenous leukemia (Joseph et al, 1982;Cohen et al, 1979), to 25-50 per cent in pre-leukemia (Saarni and Linman, 1973;Greenberg et al, 1976), particularly in patients with previous leukemogenic exposure.…”

Section: Discussionmentioning

confidence: 97%

Hypoplastic acute leukemia: Review of 70 cases with multivariate regression analysis

Berdeaux¹,

Glasser²,

Serokmann³

et al. 1986

Hematological Oncology

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Between 1971 and 1984, 22 of 190 adult patients (11.6 per cent) with acute leukemia seen at the University of Arizona had hypocellular acute leukemia (HAL), defined as lymphoblasts or myeloblasts (plus atypical promyelocytes) of greater than or equal to 30 per cent, but marrow cellularity of the core biopsy or clot section of less than or equal to 50 per cent based on a 1000 point count. These 22 patients with HAL plus the 48 previously published patients with well documented HAL (combined series of 70 patients) were evaluated in detail with multivariate analysis. The median leukocyte count was 2700/microL, hemoglobin of 8.2 g/dl, and platelet count 63,000/microL. Circulating blasts were noted in 27 of 52 patients (52 per cent). Twenty-seven of 34 patients (79 per cent) had abnormal cytogenetics. The overall median survival was 8 months (range: 0.1-48). The median survival for the 22 patients managed with supportive care alone was 4 months, 6 months for the 16 patients treated with non-aggressive induction therapy, and 13 months for the 32 patients treated with aggressive induction therapy (p less than 0.02 versus other categories). Multivariate analysis confirmed that aggressive induction therapy was a major favourable prognostic factor (p = 0.016). Multivariate analysis of the aggressively induced patients revealed that younger patients (less than or equal to 65; p = 0.04) and patients with no AHD (p = 0.09) lived longer. Thus, aggressive remission induction can be attempted in HAL and appears to contribute to prolonged survival especially under age 65 years.

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Section: Discussionmentioning

confidence: 97%

Hypoplastic acute leukemia: Review of 70 cases with multivariate regression analysis

Berdeaux¹,

Glasser²,

Serokmann³

et al. 1986

Hematological Oncology

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“…In an effort to improve diagnostic and prognostic precision, a considerable number of prognostic factors have, over the years, been identified in AML. These include leucocyte count at presentation (Bell et al, 1982), cytogenetic abnormalities (Yunis et al, 1984;Schiffer et al, 1989), morphology (Mertelsmann et al, 1980;Swirsky et al, 1986), immunological phenotype (IP) Kristensen & Hokland, 1991;Bradstock et al, 1994), and a history of prior myelodysplastic syndrome or chemotherapy for other malignant diseases (Mertelsmann et al, 1980;Pedersen-Bjergaard et al, 1981;Hoyle et al, 1989;Gajewski et al, 1989). Blast Survival and Drug Resistance in AML # 1996 Blackwell Science Ltd, British Journal of Haematology 93: [888][889][890][891][892][893][894][895][896][897] ability to form colonies in vitro (Hunter et al, 1993) are of independent prognostic significance in this disease.…”

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confidence: 99%

Relation of Blast Cell Survival and Proliferation to Chemotherapy Resistance in Aml

et al. 1996

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We have investigated the in vitro blast cell survival (viability) and drug resistance to cytosine arabinoside (Ara-C), daunorubicin (Dau), mitoxantrone (Mitox) and aclarubicin (Acla) of fresh leukaemic blast cells from 80 patients with newly diagnosed acute myeloid leukaemia (AML) employing the semiautomated colourimetric MTT(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide)-assay. In 15 cases we concurrently investigated the relation between in vitro blast cell survival (MTT assay) and blast cell proliferation (3H-thymidine incorporation) in the presence and absence of myeloid growth factors (GFs) G-CSF, GM-CSF and IL-3 (individually and in combination). A highly significant correlation was found between blast cell survival and blast cell proliferation (r = 0.87, P < 1 x 10(-4). Furthermore, in 40 evaluable adult patients who completed intravenous induction chemotherapy and were evaluable for response to chemotherapy we found a positive correlation between in vitro blast survival (MTT assay) and response to chemotherapy with high blast survival being associated with poor response to chemotherapy (P = 0.05). Moreover, in a multivariate analysis, high blast cell survival was significantly associated with high CD13 expression and monocytic phenotype (P = 0.0003 and P = 0.02, respectively). Furthermore, we found an inverse relationship between the baseline proliferation of the blasts and the magnitude of response to the GFs (P < 0.02), indicating that cells with low baseline proliferation were more readily stimulated by growth factors. Finally, we found a significant correlation between leukaemic cell survival and cellular drug resistance towards Dau (P = 0.001) and Mitox (P = 0.03), but not towards Ara-C (P = 0.68) and Acla (P = 0.13). We conclude that high in vitro leukaemic cell survival is associated with drug resistance in vivo and in vitro, and furthermore is correlated with high blast cell proliferation and some adverse prognostic factors previously identified in AML.

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“…An i(2 lq) was observed in two patients, a -2 1 in four patients Cytogenetic studies of bone marrow cells of patients suspected of therapy-related or secondary acute nonlymphocytic leukaemia (t-ANLL) or preleukaemia following treatment of other diseases with chemotherapy or radiotherapy or both have become of significant importance during the last few years, mainly for three reasons. Firstly, because the exact diagnosis of the early preleukaemic stages with refractory cytopenia relies in some cases on the demonstration of characteristic clonal chromosome abnormalities in the bone marrow of the same type as observed in patients with overt t-ANLL (Rowley et al, 1977(Rowley et al, , 1981Pedersen-Bjergaard et al, 1981: Sandberg et al, 1982: Arthur & Bloomfield, 1984 Le Beau et al, 1986). Secondly, because cytogenetic characteristics have been suggested as a prognostic factor (Pedersen-Bjergaard et d, 1984).…”

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confidence: 99%

Cytogenetic characteristics of therapy‐related acute nonlymphocytic leukaemia, preleukaemia and acute myeloproliferative syndrome: correlation with clinical data for 61 consecutive cases

Pedersen‐Bjergaard

Philip

1987

Br J Haematol

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Cytogenetic studies were performed on a new series of 23 patients with therapy-related acute non-lymphocytic leukaemia, preleukaemia or an acute myeloproliferative syndrome. In our total series of now 61 cases studied by chromosome banding techniques, at least one of the abnormalities -7, 5q-, 7q- or -5 or some related unbalanced translocations, primarily -7, +t(1q7p), was observed in 40 patients. The critical region for the deletions of chromosome no. 5 comprises bands 5q22 to 5q33 and of chromosome no. 7 bands distal to 7q22. The third most frequently involved chromosome was no. 21, rearranged at band 21q22 in the three patients with 21q+ and in one patient with 21q-. An i(21q) was observed in two patients, a -21 in four patients and a -22, +t(21q22q) and a -5, -21, +t(5p21q) in one patient each. Other characteristic abnormalities included total loss or rearrangements of the short arm of chromosome no. 17, observed in nine patients. One patient had a -12, three others had rearrangements resulting in a partial or total loss of the short arm of chromosome no. 12. A 19q+ with translocation to band 19q13 was observed in three cases, a -18 in three cases and a 3p- in four cases. Thirty-one patients with multiple chromosome aberrations experienced a significantly shorter survival as compared to 13 patients with a normal karyotype (P = 0.02) and 17 patients with one single chromosome aberration (P less than 0.01).

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Acute nonlymphocytic leukemia, preleukemia, and acute myeloproliferative syndrome secondary to treatment of other malignant diseases. Clinical and cytogenetic characteristics and results of in vitro culture of bone marrow and HLA typing

Cited by 168 publications

References 36 publications

Hypoplastic acute leukemia: Review of 70 cases with multivariate regression analysis

Hypoplastic acute leukemia: Review of 70 cases with multivariate regression analysis

Relation of Blast Cell Survival and Proliferation to Chemotherapy Resistance in Aml

Cytogenetic characteristics of therapy‐related acute nonlymphocytic leukaemia, preleukaemia and acute myeloproliferative syndrome: correlation with clinical data for 61 consecutive cases

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