Edmond Chiu

Reactivation of hepatitis B virus replication in patients receiving cytotoxic therapy: Report of a prospective study

One hundred Chinese patients who received induction cytotoxic therapy for malignant lymphoma were prospectively studied to determine the incidence, morbidity, mortality, and predisposing factors for reactivation of hepatitis B virus replication during cytotoxic therapy. In 18 (67%) hepatitis B surface antigen-positive and 10 (14%) hepatitis B surface antigen-negative patients, hepatitis developed during cytotoxic therapy (P less than 0.0001). Hepatitis could be attributed to exacerbation or reactivation of chronic hepatitis B in 13 (72%) hepatitis B surface antigen-positive patients but in only 2 (20%) hepatitis B surface antigen-negative patients (P less than 0.0001). Sudden increase or reactivation of hepatitis B virus replication gave rise to icteric hepatitis, nonfatal hepatic failure, and death in 22.3%, 3.7%, and 3.7% of patients who were positive for hepatitis B surface antigen; in 2%, 2%, and 0% of those positive for hepatitis B antibodies; and in none of those who were seronegative. Among the hepatitis B surface antigen-positive patients, male sex was the only factor that was associated with an increased risk of reactivation of hepatitis B virus replication. We recommend that hepatitis B surface antigen-positive patients with malignancies receiving cytotoxic therapy be closely monitored.

Hepatic events after bone marrow transplantation in patients with hepatitis B infection: a case controlled study

Hepatitis B reactivation following chemotherapy withdrawal may result in hepatitis, hepatic failure and death. We studied the clinical outcome and the causes of hepatic events of hepatitis B surface antigen positive recipients undergoing bone marrow transplantation. Twenty-four hepatitis B surface antigen patients were matched with 24 hepatitis B surface antigen negative patients for age, sex, CMV positive serology, underlying hematological disease and type of bone marrow transplantation. Post-BMT, there were 18 patients in the hepatitis B surface antigen positive group and four patients in the hepatitis B surface antigen negative group who suffered from hepatitis (P < 0.05). thirteen of the 18 hepatitis were related to hbv reactivation in the hepatitis b surface antigen positive group and none of the four hepatitis in the hepatitis b surface antigen negative group (P = 0.01). The hepatitis B surface antigen positive group also had an increased incidence of acute graft-versus-host disease of liver (6 vs 1, P = 0.03). However, there was no significant increase in the incidence of veno-occlusive disease (10 vs 7, P = 0.40) and persistent hepatitis (3 vs 0, P = 0.07) in the hepatitis B surface antigen positive group. Using the log-rank test, there was no significant difference in survival between the hepatitis B surface antigen positive and negative recipients.

Ceftazidime versus imipenem-cilastatin as initial monotherapy for febrile neutropenic patients.

One hundred febrile episodes in 89 neutropenic patients after cytotoxic chemotherapy were randomized to be treated with either ceftazidime or imipenem as initial monotherapy. The clinical characteristics of the two groups of patients were comparable. The response of the fever in patients who received imipenem was significantly better than that in those who received ceftazidime (77 versus 56%, respectively; P = 0.04), especially in those with microbiologically documented infection (81 versus 33%, respectively; P = 0.02). The in vitro susceptibilities and the clinical responses suggested that, with the possible exception of Pseudomonas spp., imipenem was more effective than ceftazidime in treating neutropenic infections caused by both gram-positive and -negative organisms. An additional 23 and 21% of the patients in the ceftazidime and imipenem groups, respectively, responded to the addition of cloxacillin and amikacin following failure of monotherapy. The majority of the treatment failures, relapses, and superinfections were related to resistant infective organisms such as methicillin-resistant Staphylococcus spp. and Pseudomonas spp. or disseminated fungal infections.

Autologous bone marrow transplantation for primary nasal T/NK cell lymphoma

Primary nasal T or NK cell lymphoma is rarely seen in the Western population but is more common in the Orientals. Although it often presents with localized disease, the prognosis is generally poor. Long-term remission is seen in only 50% of patients with stage I disease despite aggressive treatment with chemotherapy and radiotherapy, and is invariably fatal if disseminated. Conventional chemotherapy for relapsed disease is usually not successful. Since 1992, three patients with relapsed primary nasal T/NK cell lymphoma have received high-dose chemotherapy with autologous bone marrow rescue at Queen Mary Hospital, Hong Kong. High-dose cyclophosphamide, BCNU and etoposide were used for conditioning. Two of them had a favourable response and remained in complete remission at 12 and 44 months post-transplant. The third patient unfortunately had a systemic relapse 6 months after the transplant. It appears from this experience that, like other aggressive non-Hodgkin’s lymphomas, high-dose chemotherapy and autologous bone marrow rescue is an effective treatment for relapsed primary nasal lymphoma following failure of conventional chemotherapy and radiotherapy.

Nasal lymphoma: A retrospective analysis of 60 cases

Sixty cases of nasal lymphomas were reviewed. There were 42 men and 18 women. the median age was 49 years. the histologic types were low grade in four cases, intermediate grade in 33, high grade in seven, and unclassifiable in 16. Thirteen cases had features of polymorphic reticulosis. the immunophenotype was available in 18 cases and a majority of 67% of them were T‐cell. Forty‐one of them (68%) had clinically localized (Stage I and II) disease which often spread locally to neighboring tissues and they presented predominantly with nasal symptoms. Nasal lymphoma appeared to carry a poor prognosis. Although our patients with clinically localized disease had significantly better prognosis than those with advanced disease, the 5‐year survival of Stage I and II patients was only 55%. Chemotherapy did not appear to be more effective than radiotherapy alone in preventing relapses but the patient number was too small to allow a firm conclusion to be made. Patients with advanced disease had even poorer prognosis with a 5‐year survival of only 17%. Innovative therapy has to be developed for these patients.

Association between polyomaviruria and microscopic haematuria in bone marrow transplant recipients

The association of polyomaviruria and microscopic haematuria was studied by the use of electron microscopy (EM) and the polymerase chain reaction (PCR) in bone marrow transplant (BMT) recipients. The incidence of BK virus (BKV) and JC virus (JCV) excretion was further elucidated by means of restriction enzyme analysis of the PCR products. Polyomaviruses were detected in 43 (51.2%) of the 84 samples, 13 (30.2%) of which had a virus concentration detectable by EM. By typing with BamHI cleavage, 29 (67.4%) of the 43 positive patients were found to be excreting only BKV and the remaining 14% (32.6%) were excreting both BKV and JCV. Microscopic haematuria was present in 17 (20.2%) of 84 urine samples collected from different patients within 4 months post-transplant. The incidence of microscopic haematuria was significantly higher, 34.9% (P < 0.01), in patients with polyomaviruria than in those without (4.9%) but no difference was observed between the BKV-excreting and BKV/JCV-co-excreting patients. Microscopic haematuria was not present, however, in 53.8 and 65.2% of polyomavirus-excreting patients when virus was detected by EM and PCR respectively. While most episodes of microscopic haematuria observed were self-limiting and asymptomatic, three patients excreting polyomavirus had symptoms of cystitis and one of them had renal impairment that was otherwise unexplained. We thus conclude that polyomaviruses probably contribute to damage of urinary tract tissue in some BMT recipients.

Essential thrombocythemia with BCR/ABL rearrangement

Essential thrombocythemia (ET) was diagnosed clinically in three patients Karyotypic analysis and reverse transcription polymerase chain reaction for the bcr-abl chimeric transcript showed that two were Philadelphia chromosome (Ph) positive, bcr-abl positive, whereas the third was Ph negative, bcr-abl positive. The first patient received an allogeneic bone marrow transplantation but relapsed as localized blastic transformation, thus behaving similarly to chronic myeloid leukemia (CML). However, the other patients showed clinical courses more in keeping with ET. Essential thrombocythemia with BCR rearrangements may resemble CML but there are clinical differences. These may be due to genetic changes in addition to the BCR rearrangement.

The Spectrum of Chronic Lymphoproliferative Disorders in Chinese People

Background. Chronic lymphoproliferative disorders are considered rare in Oriental patients and are thought to constitute only 2% of all leukemias in these patients, compared to 20‐30% in Western patients. We conducted a retrospective analysis of Chinese patients with chronic lymphoproliferative disorders to define the frequency and spectrum of these disorders.

Rearrangement of immunoglobulin, T-cell receptor, and bcl-2 genes in malignant lymphomas in Hong Kong.

The pattern of malignant lymphomas in the Hong Kong Chinese population is characterized by a low incidence of Hodgkins disease and follicular lymphomas. The authors studied the immunoglobulin (Ig), T‐cell receptor (TCR), and bcl‐2 gene rearrangement in 62 cases of malignant lymphoma in this population by Southern blot hybridization. Two cases of Hodgkins disease showed no rearrangement of the Ig and TCR genes. All 42 cases of B‐cell lymphoma had Ig heavy chain (JH) rearrangement with or without additional rearrangement of the light chains (Ck and Cλ). One case of diffuse B‐cell lymphoma had additional T‐cell receptor β‐chain (Cβ) rearrangement. Sixteen of 18 cases of T‐cell lymphoma had Cβ rearrangement, and one case of T‐lymphoblastic lymphoma had additional JH rearrangement. Two of eight (25%) cases of follicular lymphoma but only one of the 34 (2.9%) cases of diffuse B‐cell lymphoma had bcl‐2 rearrangement that was detected by pFL‐1 probe. None of the 62 cases showed bcl‐2 rearrangement using the pFL‐2 probe. In conclusion, the Ig and TCR gene rearrangement pattern of the lymphomas found in Hong Kong correlates well with the T‐cell and B‐cell lineage, which is similar to reports in the white population. However, the incidence of bcl‐2 gene rearrangement in follicular B‐cell lymphoma is lower than that reported in the US but comparable with that in Japan.

Rearrangement of Immunoglobulin and T Cell Receptor Genes in Acute and Chronic Leukaemias

The pattern of immunoglobulin (Ig) and T cell receptor (TCR) gene rearrangements was determined in 87 patients with acute and chronic leukaemias and myelodysplastic syndromes by Southern blot hybridisation. All 31 cases of common, B cell and null cell acute lymphoblastic leukaemia, and B cell chronic lymphocytic leukaemia showed Ig heavy chain (JH) rearrangement, and TCR (beta-chain) rearrangement was seen in all 5 cases of T cell acute lymphoblastic leukaemia. Inappropriate JH and TCR (beta) rearrangements were present in some cases of T-ALL (60%) and common acute lymphoblastic leukaemia (18%), respectively. For the 19 patients with acute leukaemias following chronic myeloid leukaemia, blastic transformation, all 4 with lymphoid transformation and 3 of the 15 with myeloid transformation had JH rearrangement, and 3 CD10-positive lymphoid transformation and 2 myeloid transformation had their TCR (beta) genes rearranged. In conclusion, the pattern of Ig and TCR gene rearrangements correlated well with the cell lineage. However, cross-lineage rearrangements were more commonly seen in patients with acute leukaemias following chronic myeloid leukaemia blastic transformation, as compared to the de novo cases.