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Biomedical subjects

C S Chim

Publications and source records attributed to C S Chim.

At least 55 records · Page 3Linked to original sources
PubMed2003

Arsenic trioxide in comparison with chemotherapy and bone marrow transplantation for the treatment of relapsed acute promyelocytic leukaemia.

BACKGROUND: The best overall treatment strategy for patients with acute promyelocytic leukaemia (APL) in relapse with chemotherapy, bone marrow transplantation (BMT) or arsenic trioxide (As(2)O(3)) based therapy remains undefined. PATIENTS AND METHODS: We reviewed the clinical course and treatment outcome of 143 APL cases seen in four major hospitals in Hong Kong over a 10-year period. RESULTS: Complete remission (CR) was attained in 113 cases (79%) with all-trans retinoic acid (ATRA) and chemotherapy. Relapse occurred at a median of 16 months in 54 cases, with a 3-year disease free survival of 56%. Post-relapse treatment was successful in 41 cases (76%), giving an actuarial 3-year overall survival (OS) of 81% from CR1. Three different protocols were used: chemotherapy alone (n = 19), allogeneic BMT (n = 14) and an As(2)O(3)-based regimen (n = 21). Chemotherapy was associated with the highest treatment-related mortality (TRM) at 53%, giving a CR2 rate of 47%. TRM was 36% for BMT. The CR2 rate for the As(2)O(3)-based regimen was 100%, with no TRM. However, 38% of As(2)O(3) treated patients had subsequent relapses, which were further salvaged in 75% by combined As(2)O(3) plus ATRA. The actuarial OS for the three protocols leveled off by 2 years at 82% for As(2)O(3), 43% for BMT and 23% for chemotherapy (P = 0.0004). CONCLUSIONS: Our results suggest that As(2)O(3) may be superior to chemotherapy and BMT for the treatment of APL in relapse.

Adolescent↗
PubMed2002

Two cases of therapy-related acute promyelocytic leukemia (t-APL) after mantle cell lymphoma and gestational trophoblastic disease.

We report two cases of secondary acute promyelocytic leukemia (APL). One patient presented with concurrent APL and missed abortion 1 year after etoposide-based chemotherapy for gestational trophoblastic disease. A prolonged complete remission was achieved with standard chemotherapy. An elderly man developed APL 1 year after alkylator-based chemotherapy for mantle cell lymphoma (MCL). A complete clinical and molecular remission was obtained with chemotherapy and all- trans retinoic acid, followed by arsenic consolidation. Concomitant molecular relapse of APL and MCL clones was detected at 1 year, both of which responded to oral arsenic therapy. High-dose epipodophyllin is a dose risk for secondary APL, but alkylating agents may also be implicated. For patients with a history of active malignancy and heavy previous chemotherapy exposure, the use of nontoxic arsenic therapy appeared to be effective and prudent.

Adult↗
PubMed2002

Hypermethylation of gene promoters in hematological neoplasia.

Cancer cells are associated with global hypomethylation but with focal hypermethylation of specific gene promoters organized as CpG island. DNA methyltransferases, DNMT1 and 3 (3a and 3b), have been implicated in mediating maintenance and de novo methylation. Hypermethylation of gene promoters results in the inactivation of the corresponding genes, by preclusion of the formation of the transcription complex, due to the recruitment of MBP, MeCPs and histone deacetylase. This results in the deacetylation of histone and thus a compact chromatin complex unfavourable for the initiation of transcription. This methylation-associated gene silencing has been demonstrated in various genes including tumour suppressor genes (p15, p16, p73, VHL). Therefore, gene promoter hypermethylation collaborates with other mechanisms of gene inactivation such as deletion and intragenic mutations to fulfil Knudson's hypothesis. Hypermethylation may serve as a molecular disease marker for the detection of minimal residual disease. Emerging evidence suggests a possible prognostic value of gene promoter hypermethylation. Moreover, gene hypermethylation may also serve as a target for therapeutic invention by hypomethylating agents.

Animals↗
PubMed2002

Combined arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia recurring from previous relapses successfully treated using arsenic trioxide.

The optimal treatment of acute promyelocytic leukaemia (APL) recurring from relapses successfully treated using arsenic trioxide (As2O3) is undefined. Three APL patients relapsing from As2O3-induced remission were studied. Re-treatment with As2O3 failed in one patient in third relapse, and resulted in morphological but not molecular remission in another patient. Combination therapy with As2O3 and all-trans retinoic acid (ATRA), however, resulted in morphological and molecular remission in all three cases, with a follow-up time ranging from 6 to 16 months. Our results suggest a synergistic therapeutic effect between As2O3 and ATRA in APL in advanced relapse.

Adult↗
PubMed2002

Infrequent hypermethylation of CEBPA promotor in acute myeloid leukaemia.

The gene CEBPA, encoding the transcription factor C/EBPalpha, is crucial for granulocyte differentiation. We investigated the frequency of aberrant CEBPA promotor methylation with the methylation-specific polymerase chain reaction in 70 patients with acute myeloid leukaemia (AML). Two patients, both with M2 morphology, were found to have methylated CEBPA. In one of them, the fusion gene AML1/ETO, reported to cause transcription repression of CEBPA, was also present, suggesting that more than one mechanism might collaborate to suppress CEBPA gene expression. Aberrant CEBPA methylation is infrequent in AML, but may occur preferentially in the M2 phenotype.

Acute Disease↗
PubMed2002

Atypical blasts and bone marrow necrosis associated with near-triploid relapse of acute promyelocytic leukemia after arsenic trioxide treatment.

The pathologic features of acute promyelocytic leukemia (APL) with t(15;17)(q22;q21) are highly characteristic, which with few exceptions enable a firm diagnosis to be made on morphologic grounds. An APL patient in first relapse presented with large, bizarre circulating blasts and bone marrow necrosis 2 weeks after chemotherapy consolidation for an arsenic trioxide-induced remission. Although a morphologic diagnosis could not be reached, cytogenetic investigations showed a near-triploid clone with t(15;17), confirming APL in second relapse. This case showed that clonal evolution with additional karyotypic aberrations might alter the blast morphology and pathologic features in APL.

Adult↗
PubMed2002

Candida tropicalis fungaemia in adult patients with haematological malignancies: clinical features and risk factors.

Candida tropicalis fungaemia is a serious opportunistic infection. Eighteen consecutive patients with C. tropicalis fungaemia diagnosed within a five-year period were studied retrospectively. All patients had haematological malignancies treated by chemotherapy or bone marrow transplantation (BMT). Antifungal prophylaxis included nystatin (20 mg daily) for patients receiving chemotherapy, and fluconazole (200 mg daily) for patients undergoing BMT. Sixteen patients had refractory and advanced haematological malignancies. All patients were neutropenic, had central venous catheters, and were receiving treatment with broad-spectrum antibiotics at the time of fungaemia. Septic shock with skin emboli were the most common presenting features. In seven cases, fungaemia was preceded by a positive culture of C. tropicalis in the urine. Concomitant bacteraemia was found in 11 cases, of which six cases were due to Staphylococcus aureus. The overall mortality rate was 56%. The predominance of chemotherapy-treated patients developing fungaemia in this series might be attributable to the omission of fluconazole prophylaxis. The clinicopathologic features and risk factors identified in this study may help design better treatment strategies for this often-lethal complication.

Adolescent↗
PubMed2002

Analysis of Clonality in Kimura's Disease.

Kimura's disease is a chronic inflammatory disorder of unknown etiology. A 62-year-old man presented with asymptomatic cervical lymphadenopathy associated with eosinophilia and increased serum immunoglobulin E. Excision biopsy showed Kimura's disease. Three years later another groin lymph node appeared and showed similar pathologic features. Polymerase chain reaction for Ig heavy chain and T-cell receptor (TCR) genes on DNA extracted from the cervical lymph node showed smear patterns. However, polymerase chain reaction for TCRdelta gene showed a clonal rearrangement. Sequencing showed a complete VDJ rearrangement (Vdelta1-N-Ddelta2-N-Jdelta), confirming the presence of a clonal T cell population. The same clonal TCRdelta rearrangement was amplified by polymerase chain reaction from the groin lymph node biopsied 3 years later. These results showed that the primary and recurrent lesions were biologically related. Furthermore, the presence of identical T cell clones in different sites and at different times suggested that a clonal T cell population might have contributed to the pathogenesis in this case of Kimura's disease.

Angiolymphoid Hyperplasia with Eosinophilia↗