Two Cases of Acute Leukemic Transformation with a Chromosome 17 Abnormality and p53 Overexpression Evolving from Essential Thrombocythemia

Essential thrombocythemia (ET) is a clonalmyeloproliferative disorder that can rarely transform into acute leukemia in 1~5% of cases. A recent study has found that a significant proportion of leukemic cases from ET were associated with a cytogenetic abnormality (17p deletion). Herein, we report two cases of acute myeloid leukemic transformations harboring a 17p abnormality from a series of 119 ET patients. The first case, a 48-year-old female, developed acute myeloid leukemia with maturation (AML-M2) accompanying myelodysplasia was diagnosed 6.1 years after the initial diagnosis of ET. She was treated with hydroxyurea. Her karyotype showed a monosomy 17. The second case, a 61-year-old male, developed acute megakaryoblastic leukemia (AML-M7) with a very complex hyperdiploidy including addition of 17p13 that developed 6.5 years after the initial diagnosis. He was treated with hydroxyurea and anagrelide. The immunohistochemistry showed p53 overexpression in both cases. Our cases support the specificity of chromosome 17 abnormality and p53 overexpression in acute leukemic transformation from ET.

A Case of Myelodysplastic Syndrome in a Renal Transplant Recipient / 대한신장학회잡지

A 44-year-old man treated with azathioprine, cyclosporine and prednisolone for 7.5 years after allogeneic renal transplantation was admitted because of exertional dyspnea, fatigue and pancytopenia which were found 3 months ago. He had been on hemodialysis for renal failure of unknown cause for 8 months before the renal transplantation. Bone marrow examination showed hypercellularity, erythroid hyperplasia and 7% of myeloblast, consistent with the diagnosis of myelodysplastic syndrome. Cytogenetic study showed chromosomal abnormalities:deletion of chromosome 5, monosomy 7, trisomy 8, monosomy 14 and deletion of chromosome 17. Immunosuppressive agents were discontinued and he was treated with transfusion, G-CSF, and combination chemotherapy including topotecan and Ara-C. Graft kidney function was normal before and after the treatment, but the clinical course was fatal because of leukemic transformation and eventually sepsis. Although therapy induced myelodysplastic syndrome was rare in renal allograft recipients, thorough evaluations including bone marrow biopsy and cytogenetic study are recommended in patients with anemia of unknown etiology.

A Clinical Observation of Childhood Myelodysplastic Syndrome / 대한소아혈액종양학회지

BACKGROUND: Childhood myelodysplastic syndrome(MDS) is a heterogenous disease complex which has characteristics of cytopenia in one or more hemopoietic cell lines in peripheral blood and of dysmorphisms of hemopoietic precursors in bone marrow, but quite different from adult one. We experienced 22 patients with childhood myelodysplastic syndrome during 9 years from 1987 to 1995 in the Department of Pediatrics, Inje University College of Medicine, Pusan Paik Hospital, Pusan, Korea and performed a clinical study about them to analyze the clinical and hematological features and treatment outcome retrospectively. METHOD: We analyzed their clinical features including age and sex distribution, chief complaints and physical findings on first admission, distribution of subtypes, hematologic features including initial hemoglobin, total WBC and platelet count, and treatment outcome including leukmic transformation and prognostic scores. RESULTS: 1) Of the total 22 patients, 10 were in 0-4 years of age on first admission, 8 in 5-9, and 4 above 10 years of age. The male : female sex ratio was 2.1 : 1. 2) Of the 22 patients, chief complaints on first admission were bleeding tendency in 9 patients(40.9%), pallor in 8(36.4%) and fever in 3(13.6%), in order, and physical findings on first admission were purpura or ecchymoses in 17(77.3%), anemia in 15(68.2%) and hepatosplenomegaly in 8(36.4%), in order. 3) Hematologic findings on first admission were as follows : hemoglobin levels were below 3 g/dl in 1 patient(4.5%), 3-6 g/dl in 10(45.5%), and 6-9 g/dl in 11(50.0%). Initial WBC counts were below 5,000/mm3 in 13 patients(59.1%), 5,000-10,000/mm3 in 5(22.7%) and above 10,000/mm3 in 4(18.2%). Initial platelet counts were below 20,000/mm3 in 10(45.5%), 20,000-50,000/mm3 in 5(22.7%), 50,000-100,000/mm3 in 5(22.7%) and above 100,000/mm3 in 2(9.1%). 4) Of the 22 patients, 12 patients(54.6%) were RA type, 1(4.6%) RAS, and 3(13.6%) RAEB, RAEB-T and JCML types, respectively. 5) According to prognostic scores by Mufti et al(1986), none were in 'good' group, 17 patients(89.5%) in 'intermediate' group with 39.5 months of mean duration of survival(range 4-95 months) and 2(10.5%) in 'poor' group with 18 months of mean duration of surviral(range 17-19) until the last follow-up. However, the subtypes and clinical status seemed not to be related to the prognostic scores. 6) Sixteen patients were treated with low dose cytosine arabinoside(10 mg/m2/12hrs), of whom 7 patients gained long-standing event-free survival, whose treatment regimen was changed to oral 6-TG about 2 years later. All 3 of JCML were treated with A-Triple-V regimen, one of whom was died of sepsis, one was transformed into AML and died of sepsis, while the remained one gained long-standig event-free survival (62 months). 7) Leukemic transformation into AML occured in 7 patients(RA 1, RAEB 2, RAEB-T 3, JCML 1), 6 of whom were dead, while one gained long-standing event-free survival of 34 months. CONCLUSION: We concluded that RA was the most dominant type among our patients, and the frequency to transform into AML was 31,8%, and 31.9% of the patients had long-term survival, and that reliability of prognostic scoring system by Mufti et al(1986) was not high.

A Case of Leukemic Transformation in Essential Thrombocythemia Treated with Hydroxyurea / 대한혈액학회지

Essential thrombocythemia is a myeloproliferative disorder, characterized by marked thrombocytosis and marrow megakaryocytic hyperplasia. Although the major causes of morbidity and mortality are bleeding and thromboembolic events, the long-term prognosis is favorable and leukemic transformation is rare. We report a case of acute leukemia following treatment of Philadelphia chromosome-negative essential thrombocythemia with hydroxyurea for 4 years with a brief review of literature.

Testicular Leukemia

Leukemic infiltration of the testes has been relatively rare disease. But increased survival due to advance in the treatment of childhood leukemia has been associated with an increase in incidence of leukemic infiltration of the tests. Six of 66 male children with acute lymphocytic leukemia and 2 of 2 male children with leukemic transformation on non-Hodgkin's lymphoma, who have been admitted to our pediatric department during past 7.5 years period, from January, 1974 to June, 1981 developed testicular leukemia. This represents an incidence of 11.8% and the median age was 6.6 years(9 mo. to 14 yrs). All patients were symptom free despite testicular enlargement. Testicular enlargement was initial presenting manifestation in two patients. The enlargement was unilateral in 5 and bilateral in 3. Initial white blood cell count was greater than 100,000/mm3 in five patients and was less than 10,000/3 in other three. Microscopic findings on specimens were leukemic infiltration mainly in the interstitial spaces and atrophy of spermatogenic cells. Four patients developed testicular relapse during bone marrow remission. Hepatosplenomegaly and lymphadenopathy were present in 5 and 6, and these appeared to imply an increased risk of testicular relapse. The median duration from diagnosis to testicular relapse was 33.5 months(2 mo. to 93 mo.). Three patients developed subsequent relapses(CNS; 2, BM; 1) 1.5 to 26 months after the testicular relapse, the median interval being 14.5 months. Radiotherapy with chemotherapy has resulted clinical improvement, but only one patient showed long survival without relapse.