Y. M. Yeung

Organ-specific hemosiderosis and functional correlation in Chinese patients with thalassemia intermedia and hemoglobin H disease

We performed MRI assessment in 37 adult Chinese patients with thalassemia intermedia and hemoglobin H disease. Despite abnormal ferritin and liver T2*, only 5% of patients had cardiac hemosiderosis. The two patients with reduced ejection fraction had normal cardiac T2*. Half of the cases showed pituitary and pancreatic iron loading. Subclinical endocrine abnormalities (HOMA, insulin growth factor) showed correlation with pancreatic, pituitary, and cardiac MRI values. Prospective data with serial functional and imaging monitoring is needed to verify the utility for chelation to improve cardiac and endocrine function in this group of patients.

Cytomegalovirus infection associated with clonal proliferation of T-cell large granular lymphocytes: causal or casual?

Clonal proliferation of T-cell large granular lymphocytes (LGL) is an indolent disorder characterized by splenomegaly, lymphocytosis and frequent manifestations of immune disturbances. The LGL are CD3(+) CD4(-) CD8(+) CD56(-). The clonality of the tumor cell population is often only demonstrable by T-cell receptor (TCR) gene rearrangement study because chromosomal abnormality is distinctly rare. We describe a case of T-cell LGL leukemia that presented initially as cytomegalovirus infection. The leukemic LGL are shown to be clonal by both TCR gene rearrangement and chromosomal studies. They persist after subsidence of the cytomegalovirus infection.

Molecular Characterization of der(15)t(11;15) as a Secondary Cytogenetic Abnormality in Acute Promyelocytic Leukemia with Cryptic PML-RARα Fusion on 17q

A case of acute promyelocytic leukemia (APL) with cryptic PML-RAR alpha fusion on 17q and add(15p) as a secondary abnormality was characterized using molecular cytogenetic techniques. Spectral karyotyping (SKY) showed that chromosome 11 material was added to 15p, forming a der(15)t(11;15), which was refined to der(15)t(11;15)(q13.2;p13) with information obtained by comparative genomic hybridization (CGH). Interstitial insertion of chromosome 15 material into chromosome 17q was found by fluorescence in situ hybridization (FISH) with whole chromosome painting (WCP) probes. This study illustrates the necessity of a combination of molecular cytogenetics to decipher complex karyotypic abnormalities and cryptic translocations in leukemia.

Fatal diffuse alveolar damage complicating acute myeloid leukemia with abnormal eosinophils and trisomy X.

Abstract. We describe a case of acute myeloid leukemia (AML) with abnormal eosinophils in a 44-year-old Chinese woman that was complicated by diffuse alveolar damage (DAD) and pulmonary hemorrhage (PH) shortly after induction chemotherapy. Cytogenetic study of bone marrow cells at diagnosis showed a rare aberration of trisomy X (+X) as the sole acquired karyotypic abnormality. We speculate that tissue damage by cellular constituents of the abnormal eosinophils that were released on cell lysis after chemotherapy might be etiologically linked to the occurrence of fatal pulmonary complications.

Treatment of CD33 positive refractory acute lymphoblastic leukemia with Mylotarg.

Acute lymphoblastic leukemia (ALL) accounts for approximately 15 – 20% of all adult acute leukemias, and the incidence increases with age. ALL is a heterogeneous disorder, and response to therapy can vary dramatically, depending on the clinical features present during diagnosis. More than 70% of afflicted children achieve long-term disease-free survival, while only 20 – 38% of adults do so. The study of Kantarjian et al. compared patients treated with hyper-CVAD with those treated with vincristine, doxorubicin and dexamethasone regimens; it showed a better CR rate (91% vs. 75%, P5 0.01) and CR rate after one course (74% vs. 55%, P5 0.01) and better survival (P5 0.01); a smaller percentage had more than 5% blasts at day 14 (34% vs. 48%, P5 0.01) [1]. Calicheamicin, a highly potent antitumour antibiotic that cleaves double-stranded DNA at specific sequences, was conjugated to a humanized anti-CD33 monoclonal antibody to produce Mylotarg (gemtuzumab ozogamicin; CMA-676; Wyeth Laboratories, Philadelphia, PA). Mylotarg was evaluated in a dose-escalation trial with relapsed or refractory CD33-positive AML patients. Thirty percent of patients treated with Mylotarg obtained remission as characterized by 5% or less blasts in the marrow, recovery of neutrophils to at least 1500/mL, and RBC and platelet transfusion independence [2]. Twenty percent of ALL is also CD33 positive. In vitro and in vivo experiments have shown that Mylotarg is active against CD33-postitive ALL [3]. Several case reports suggested that Mylotarg is able to induce remission in paediatric CD33-positive ALL [4 – 6]. We reported a 20-year-old male with newly diagnosed precursor B lymphoblastic leukemia. On presentation, he complained of generalized joint pain with symptom of anaemia. Complete blood picture showed leucoerythroblastic blood with 15% blasts in peripheral blood (complete blood picture: Hgb 8.4 d/dL, WBC 4.556 10/L, PLT 1866 10/L, absolute neutrophil count 0.866 10/L). The marrow is heavily infiltrated by blasts constituting 95% of the cells. On examination, analysis of the blood and marrow by flow cytometry showed that the blasts are positive for CD19, CD22, cytCD79a, CD10, HLADR, CD34, CD13, CD33 (98.7%) and negative for CD117, cytMPO, CD14, CD3, CD7, CD56. Cytogenetic study showed complex karyotype with multiple structural changes such as 46, XY, add(1)(q43), add(9)(q34), add(21)(q22)[2]/92, XXYY[1]/46 and XY[15]. Interphase fluorescence in-situ hybridization (FISH) showed no evidence of BCR/ABL fusion. He was given hyperfractionated cyclophosphamide therapy and high-dose cytarabine (ara-C) and methotrexate treatment. It showed refractory disease in re-staging bone marrow biopsy with 25% blasts. We treated him with ICE protocol for the refractory leukemia [7,8]. However, he was complicated by neutropenic sepsis from oro-dental infection which was subsequently controlled by antibiotic and G-CSF support. Repeated bone marrow biopsy showed 19% blasts. Flow cytometry showed that the blast cells are homogeneously strongly positive for CD33 (97.24%) (Figure 1). We decided to try Mylotarg (anti-CD33) based on the ground that the blasts are strongly positive for

Two balanced and novel chromosomal translocations in myeloid malignancies: characterization by multiplex fluorescence in situ hybridization

We describe two novel chromosomal translocations in two cases of leukemia in which these translocations were further characterized as the sole acquired karyotypic abnormality by mutliplex fluorescence in situ hybridization (M-FISH). They comprised a case of acute myeloid leukemia with t(6;10)(q21;p12) and a case of chronic myelomonocytic leukemia with t(5;12)(q34;q24). To the best of our knowledge, these two balanced translocations are novel and are hitherto unrecognized in hematologic malignancies. While the clinical and pathogenic significance of these translocations remains to be defined, the present report illustrates that M-FISH technology contributes to the exclusion of subtle or cryptic translocations in sole karyotypic aberrations and the confirmation of novel chromosomal arrangements in neoplastic disorders.