Risk of hepatitis B reactivation and the role of novel agents and stem-cell transplantation in multiple myeloma patients with hepatitis B virus (HBV) infection.

BACKGROUND: The purpose of the study is to analyse the prevalence of hepatitis B virus (HBV) infection and its incidence of reactivation among multiple myeloma (MM) patients treated in the era of novel therapy in an endemic Asian setting. PATIENTS AND METHODS: From 2000 to 2008, 273 patients with newly diagnosed MM were screened for the presence of hepatitis B virus surface antigen and HBV core antibody. HBV-infected patients were prospectively followed for reactivation with serial monitoring of serum alanine transferase and HBV DNA load. The patterns of HBV reactivation in relation to treatment received, exposure to high-dose therapy with autologous stem-cell transplantation (HDT/ASCT) and novel agents were studied. RESULTS: The prevalence of HBV infection was 5.5%. Three cases of HBV reactivation despite lamivudine prophylaxis were reported. Two patients reactivated 3-5 months after HDT/ASCT while receiving thalidomide maintenance and one reactivated 3 years after HDT/ASCT and shortly after bortezomib salvage therapy. Emergence of a mutant HBV strain was documented in one patient. CONCLUSIONS: Use of prophylaxis may reduce but will not preclude HBV reactivation. Highest risk occurs during immune reconstitution phase of HDT/ASCT. The role of immunomodulatory agents in HBV reactivation needs to be further elucidated. Separate HBV prophylaxis and surveillance guidelines ought to be developed for patients with MM.

Characterization of hemopoietic engraftment kinetics and development of secondary cytopenia in AML post auto-SCT and its correlation with survival outcome.

We performed a single center retrospective analysis of 84 autologous hemopoietic stem cell transplants done for AML to characterize the pattern of hemopoietic engraftment, post-transplant cytopenia and their impact on survival outcome. Following autologous transplant and engraftment, 30 patients (35.7%) had a transient secondary decline in their plt counts, which was not associated with graft rejection, relapse or infection. The median time to onset of thrombocytopenia was 59 days post transplant, with spontaneous recovery after a median period of 41 days. A secondary decline in ANC also occurred in eight patients. Patients with secondary plt decline had a significantly earlier primary plt engraftment (median 15 days) and a trend towards earlier neutrophil engraftment compared with patients who maintained steady plt counts (median 21 days). There was a trend towards a lower incidence of secondary plt decline in patients who received BM stem cells compared with those who received PBSC. No cause was evident for the occurrence of a secondary cytopenia, and it did not adversely affect survival. We conclude that secondary cytopenia is a common and harmless occurrence after autologous transplant especially from PBSC graft.

Treatment and outcome of acquired haemophilia A with a standard conventional regimen in a cohort without associated conditions.

Acquired haemophilia A (AH) is a rare bleeding disorder with significant risk of mortality. We conducted a study on the treatment and outcomes of patients with AH diagnosed between 1998 and 2004 in our institution. Fourteen patients (age range 17-89, median 64) were followed-up from between 10-64 months (average 32 months). Inhibitor levels ranged from 5 to 450 BU. Ten patients required either recombinant activated factor VIIa or prothrombin complexes for control of bleeding. All patients received a standard immunosuppressive regimen of prednisolone 1 mg kg day(-1) and oral cyclophosphamide 50-100 mg day(-1). In addition, nine patients received intravenous immunoglobulin. Complete remission (CR) was achieved in 88% (eight of nine evaluable patients) over durations ranging from 5-78 days (average 35 days). There were three mortality; from bleeding, sepsis and cerebral infarct. Two patients were lost to follow-up. There were no relapses among patients achieving CR. Conditions associated with AH were not identified at diagnosis or subsequent follow-up in all patients. This series represent one of the largest aetiologically and treatment-wise, uniformed cohort of AH patients. Despite toxicity concerns, the combination of prednisolone and cyclophosphamide remain an effective regimen and should be among the first line of treatment choices, with careful patient selection.

Fludarabine in comparison to alkylator-based regimen as induction therapy for chronic lymphocytic leukemia: a systematic review and meta-analysis.

The superiority of Fludarabine over conventional therapy as primary induction therapy for patients with chronic lymphocytic leukemia (CLL) has been shown in several studies but no studies have yet reported a pooled estimate of the treatment effect. We performed a systematic review of evidence from 5 randomized controlled trials involving approximately 1300 patients with CLL, comparing Fludarabine with several alkylator-based combination regimens in the primary treatment of CLL. Complete response rate was significantly higher for Fludarabine compared to alkylator-based chemotherapy (RR 1.87, 95% CI 1.10-3.19, P=0.02), while overall response, though superior, did not reach statistical significance (RR 1.22, 95% CI=0.88-1.69, P=0.24). Overall survival was similar for Fludarabine and alkylator-based therapy (the pooled log hazard ratio of death, HR=-0.05, 95% CI=-0.36-0.26, P=0.75). Infection rate was significantly higher (RR 1.58, 95% CI=1.10-2.27, P=0.01), but there was no significant difference in the incidence of thrombocytopenia, neutropenia and anemia. Therefore, this meta-analysis supports the findings that Fludarabine as an induction agent for patients with CLL yields a better clinical response with acceptable toxicity when compared with alkylator-based combination therapy, but without a survival benefit by 5-6 years of follow up.