Morphological diagnoses of the Japan Adult Leukemia Study Group acute myeloid leukemia protocols: Central review

Abstract

A morphological review system of the Japan Adult Leukemia Study Group has developed from the AML-87 through the AML-92 experience. We reviewed 1427 (90%) of 1592 cases enrolled in the AML-87, -89, or -92 protocols for morphology; 1408 (88%) were eligible. The rate of diagnostic concordance between each institute and the Committee on Morphological Diagnosis ranged from 76% to 80%. Acute myeloid leukemia (AML) subtypes were as follows: AML M0, 27 (2%); M1, 179 (13%); M2, 472 (34%); M3, 358 (25%); M4, 265 (19%); M5, 57 (4%); M6, 39 (3%); and M7, 11 (1%). The reason for the high number of patients with AML M3 is that many M3 patients were enrolled in the AML-92 protocol, which contained all-trans-retinoic acid. AML M0, M6 and M7 belonged to the poor prognostic groups. Auer bodies were found in 284 (53%) of 538 patients who survived significantly longer than those without Auer bodies in AML-87/-89. In AML-92 except for AML M3, 259 (43%) of 602 cases were Auer+ and also showed better survival rates. The survival of patients with >50% myeloperoxidase (MPO)-positive blast cells was better than those with < or =50% MPO+ blast cells in AML-87/-89. This trend was also seen in AML-92 excluding M3. AML with trilineage dysplasia (AML/TLD) is characterized as a subtype of de novo AML that shows morphological dysplasia of mature hematopoietic cells on a background of leukemic blast cells The number of patients with AML/TLD was 89 (16.5%) of 545 patients reviewed in AML-87/-89. AML-92, except for M3, showed a higher rate of patients with TLD (161 cases; 27.6%) because there were no patients with TLD in the AML M3 group. Survival rates for AML/TLD were worse than those for AML/non-TLD in both the AML-87/-89 and -92 protocols. Eighty percent of all cases (793/986) entered in AML-92 were analyzed cytogenetically. Fifty-one cases were not available for karyotyping because of a lack of mitoses or inappropriate preparations. The most frequent karyotype was normal, which accounted for 34.2%. The t(15;17), t(8;21), and inv(16) karyotypes, which are regarded as good risk factors, were 23.8%, 9.2%, and 1.6%, respectively. Abnormal chromosomes 5, 7, t(9;22), and t(6;9) were considered to be poor or intermediate risk factors As a new system of karyotyping begins in the ongoing AML protocol, useful chromosomal data will be obtained in the near future.

Clinical and Hematological Profile of Acute Myeloid Leukemia (AML) Patients of Sindh

“…Table 2 shows comparison of AML subtypes with our study. As we look into the frequency of FAB types in different age groups, it was noted that AML-M3 subtype though common below 50 years of age, not a single case of M3 was seen in patients older than 50 years, the finding comparable with a study done in Japan on elderly patients of Acute Myeloid Leukemia [18]. In Acute myeloid leukemia extramedullary infiltration by leukemic cells may cause lymphadenopathy, splenomegaly or hepatomegaly.…”

“…The FAB classification has been the major system used by hematologists for more than 20 years. This classification is best suited for places where sophisticated investigations like cytogenetic studies and molecular studies are not available [18]. In our study most common subtype was AML-M1 followed by equal number of M3 and M4.…”

Expression of myeloperoxidase enhances the chemosensitivity of leukemia cells through the generation of reactive oxygen species and the nitration of protein

“…It is very interesting that AML cases with favorable karyotypes such as t(15;17), t(8;21) and inv (16) usually have a high percentage of MPO-positive blasts. 20,21 Recently, a polymorphism in the promoter region of the MPO gene was shown to relate to survival of breast cancer patients after chemotherapy: 22 patients having lower transcriptional activity of MPO (G to A conversion at the À463 nucleotide of the MPO gene) showed significantly worse prognosis. The authors of this report concluded, in concordance with our current observation, that the oxidative stress would modify prognosis after chemotherapy for breast cancer.…”

The percentage of myeloperoxidase-positive blast cells is a strong independent prognostic factor in acute myeloid leukemia, even in the patients with normal karyotype

“…[10][11][12][13] The ECOG study showed that patients with less than Blast MPO Positivity Predicts AML Prognosis T Matsuo et al 50% MPO-positive blasts showed a low CR rate (52.6%), while patients with more than 50% MPO-positive blasts had a significantly better CR rate (85.3%) in the AML M1 subtype (P ¼ 0.003).…”

“…[4][5][6][7][8][9] Thus, the percentage of MPO-positive blast cells has generally been considered to be very important for the diagnosis but not for the prognosis of AML, although a few studies have previously shown the prognostic significance of MPO in AML. [10][11][12][13] Other than the clinical features such as age or performance status, karyotypes of leukemia cells are considered as the most important and independent prognostic factor for AML. The importance of cytogenetics was clearly shown in a previous MRC report, 14 indicating that t(8;21), t (15;17), and inv(16) predicted a favorable outcome and complex karyotype, À5, del(5q), À7, and abnormalities of 3q defined an adverse group with poor prognosis.…”