Ying-Chung Hong

Randomized Controlled Trial of Entecavir Prophylaxis for Rituximab-Associated Hepatitis B Virus Reactivation in Patients With Lymphoma and Resolved Hepatitis B

PURPOSE The role of antiviral prophylaxis in preventing hepatitis B virus (HBV) reactivation before rituximab-based chemotherapy in patients with lymphoma and resolved hepatitis B is unclear. PATIENTS AND METHODS Eighty patients with CD20(+) lymphoma and resolved hepatitis B were randomly assigned to receive either prophylactic entecavir (ETV) before chemotherapy to 3 months after completing chemotherapy (ETV prophylactic group, n = 41) or to receive therapeutic ETV at the time of HBV reactivation and hepatitis B surface antigen (HBsAg) reverse seroconversion since chemotherapy (control group, n = 39). RESULTS Fifty-eight patients (72.5%) were positive for hepatitis B surface antibody, and HBV DNA was undetectable in 50 patients (62.5%). During a mean 18-month follow-up period, one patient (2.4%) in the ETV prophylactic group and seven patients (17.9%) in the control group developed HBV reactivation (P = .027). The cumulative HBV reactivation rates at months 6, 12, and 18 after chemotherapy were 8%, 11.2%, and 25.9%, respectively, in the control group, and 0%, 0%, and 4.3% in the ETV prophylactic group (P = .019). Four patients (50%) in the control group had HBsAg reverse seroconversion after HBV reactivation. The cumulative HBsAg reverse seroconversion rates at months 6, 12, and 18 since chemotherapy were 0%, 6.4%, and 16.3% in the control group, respectively, which were significantly higher than those in the ETV prophylactic group (P = .032). Patients with detectable or undetectable viral load could develop HBV reactivation and HBsAg reverse seroconversion. CONCLUSION Undetectable HBV viral load before chemotherapy did not confer reactivation-free status. Antiviral prophylaxis can potentially prevent rituximab-associated HBV reactivation in patients with lymphoma and resolved hepatitis B.

Hair follicle: a reliable source of recipient origin after allogeneic hematopoietic stem cell transplantation.

Blood, buccal swab and hair follicles are among the most commonly used sources for forensic science, parentage testing and personal identification. A total of 29 patients who have had a sustained engraftment from 15 months to 21.5 years after allogeneic hematopoietic stem cell transplantation (HSCT) without rejection, relapse or chronic GVHD involving oral mucosa were enrolled for a chimerism study. PCR-amplified short tandem repeat analyses were conducted per patient every 3 months for at least three consecutive times. The results for blood were all donor type except one who had a mixed chimerism, 14.5 years after receiving a transplant for lymphoma. As for buccal swab, mixed chimerism ranging from 10 to 96% donor origin was noted for 28 recipients except the one who had mixed chimerism of blood and retained total recipient type. In contrast, hair follicles were 100% recipient type for the entire group. It is concluded that the hair follicle is devoid of adult stem cell plasticity and may serve as a reliable source of recipients origin when pre-transplant DNA fingerprinting or reference DNA is not available for people who have successfully received allogeneic HSCT while in need of a personal identification.

Low absolute lymphocyte count and addition of rituximab confer high risk for interstitial pneumonia in patients with diffuse large B-cell lymphoma

Several small-scale studies have reported pulmonary toxicity among patients with diffuse large B-cell lymphoma (DLBCL) receiving rituximab-containing chemotherapy, though whether the use of rituximab predisposes to interstitial pneumonia (IP) remains unclear. This retrospective study was intended to identify the characteristics and risk factors of IP in patients with DLBCL. Between 2000 and 2009, 529 consecutive patients with DLBCL receiving first-line tri-weekly COP- or CHOP-based chemotherapy with or without rituximab were enrolled as subjects. IP was defined as diffuse pulmonary interstitial infiltrates found on computed tomography scans in conjunction with respiratory symptoms. IP was observed in 26 patients (4.9%), six of whom were confirmed with Pneumocystis jirovecii pneumonia. The median number of chemotherapy courses before IP was four cycles. Using multivariate analysis, absolute lymphocyte count less than 1 × 109/l at diagnosis [odds ratio (OR) 2.75, p = 0.014] and the addition of rituximab to chemotherapy (OR 4.56, p = 0.003) were identified as independent risk factors for IP. In conclusion, the incidence of IP is increased in patients with DLBCL receiving rituximab-containing chemotherapy. Specific subgroups with lymphopenia at diagnosis may justify close scrutiny to detect pulmonary complications.

High incidence of oral squamous cell carcinoma independent of HPV infection after allogeneic hematopoietic SCT in Taiwan

Hematopoietic SCT (HSCT) is a well-recognized therapeutic procedure to prolong life and cure patients with life-threatening hematological malignancies; however, the risk of developing secondary carcinoma may increase in long-term survivors. The objective of this study was to determine the incidence and risk factors for secondary squamous carcinoma after HSCT. Between 1984 and 2004, 170 allogeneic HSCT recipients aged >15 years, who had survived for >5 years were enrolled. Demographic data and the characteristics of secondary carcinoma were collected and analyzed for the determination of the incidence and risk of developing secondary carcinoma. Eight patients developed secondary carcinoma, including five oral squamous cell carcinomas, one esophageal, one gastric and one ovarian carcinoma, but no cutaneous carcinomas were detected at a median follow-up of 14.1 years (range, 5.1–23.3 years) after HSCT. The accrual 10-year cumulative incidence of secondary carcinoma was 2.89%. In univariate and multivariate analyses, chronic GVHD and age >40 years at the time of HSCT were both significant risk factors independently associated with the development of secondary carcinoma. Thus, the occurrence of secondary carcinoma is one of the late complications in patients undergoing HSCT. Oral squamous cell carcinoma was more common in our patients after HSCT, indicating the need for lifelong surveillance of the oral cavity. Moreover, because of the relatively long latency in developing secondary carcinoma, extended follow-up is required for a thorough understanding of the incidence and characteristics of secondary carcinoma after HSCT.

Frequency of surveillance computed tomography in non-Hodgkin lymphoma and the risk of secondary primary malignancies: A nationwide population-based study

With increasing usage of computed tomography (CT) for lymphoma patients receiving curative‐intent treatment, development of secondary primary malignancy (SPM) related to radiation from CT scans becomes an emerging issue in these long‐term survivors. We conducted a nationwide population‐based study analyzing non‐Hodgkin lymphoma (NHL) patients receiving curative‐intent treatment between January 1997 and December 2010. Patients were divided into two populations by the medium number of CT performed. The cumulative incidence of SPM in these two groups was compared using the Kaplan–Meier method. Propensity score matching was applied to eliminate potential confounders. Group stratification and multivariate analyses calculated by Cox proportional hazard models using competing risk analyses adjusted for mortality were performed to identify independent predictors for SPM. Patients receiving >8 CT scans had a significantly greater risk for developing SPM (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.61–3.13; p < 0.001) than those with ≤8 scans and this difference remained significant even after correction with propensity score matching. Among the 180 SPM identified, those receiving more CT scans had significantly higher SPM incidence in cancers of the breast (HR 11.22), stomach (HR 5.22) and liver and biliary tract (HR 2.18) in comparison to those with less exposure. The risk of SPM was estimated to increase 3% per one more CT scan performed. Our study demonstrated that after curative‐intent treatment, patients with NHL receiving more frequent surveillance CT scans would have an increased risk of SPM.

Pre-existing diabetes mellitus in patients with multiple myeloma

Type 2 diabetes mellitus is present in approximately 10% of patients at diagnosis of multiple myeloma (MM) and is associated with increased risks of adverse events caused by novel antimyeloma agents. However, the impact of type 2 diabetes on the survival of patients with MM has not been studied.

Clinicopathologic features and outcome of acute erythroid leukemia based on 2008 revised World Health Organization classification

Abstract We report 67 patients with acute erythroid leukemia (erythroleukemia) based on the World Health Organization (WHO) 2008 classification. Reviewing the clinicopathologic features, cytogenetics and outcomes, the characteristics of erythroleukemia resembled myelodysplastic syndromes (MDS). Patients with poor performance status, advanced anemia and poor-risk cytogenetics had significantly inferior outcomes. The International Prognostic Scoring System (IPSS) for MDS is useful to differentiate the prognosis of erythroleukemia.

Clinical features and prognostic factors of angioimmunoblastic T-cell lymphoma in Taiwan: a single-institution experience

Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of peripheral T-cell lymphoma that carries a poor prognosis. This study retrospectively analyzed patients with AITL from a single institution in Taiwan, aiming to define the clinical features and prognostic factors. Patients with AITL treated at our institution from February 1988 through January 2010 were enrolled. Factors associated with overall survival (OS) were determined by statistical methods. A total of 31 Taiwanese patients (21 males) were identified. The median age was 74 years (range, 27–90). Among all patients, 67.7% were Ann Arbor stage III or IV, 58.1% presented with B symptoms, 48.4% had hypoalbuminenia (<35 g/L), and 63.3% had elevated lactate dehydrogenase (LDH) at diagnosis. First-line chemotherapy was mostly CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisolone)-based and complete response (CR) was achieved in 25% of patients. The actuarial 2-year survival rate was 38.7%, and the median OS was 14.9 months. In multivariate analysis, initial presentation with fever (p = 0.035), advanced stage (p = 0.024), and failure to achieve CR (p = 0.029) were independent adverse factors associated with poorer OS. Interestingly, OS did not differ whether chemotherapy regimens contained anthracycline or not. Taiwanese patients with AITL were usually elderly. Despite the prognosis being generally poor, patients with AITL should be treated with the goal of achieving CR, regardless of anthracycline- or non-anthracycline-based chemotherapy.

Severe Extensive Bone Marrow Necrosis From Miliary Tuberculosis Without Granulomas and Pulmonary Presentations

Bone marrow necrosis (BMN) is a rare clinicopathologic entity caused by hypoxemia after failure of the microcirculation, which frequently manifests with bone pain, fever, and peripheral cytopenia. In most reported cases of BMN resulting from miliary tuberculosis (TB), the presence of marrow granulomas, pulmonary infiltrates and/or extrapulmonary involvement is common. We report a female patient with extensive BMN from miliary TB, whose initial presentation was only severe peripheral cytopenia with extensive marrow necrosis, with neither evident pulmonary manifestations nor granulomas in the marrow biopsy. Serial Ziehl-Neelsen stains and Mycobacterium tuberculosis cultures were negative. The diagnosis of suspected miliary TB was made by consecutive positive results from polymerase chain reaction analysis for TB of marrow samples at 2 separate examination time points and a good treatment response to anti-TB therapy. Magnetic resonance imaging showed a geographic pattern of multiple signal abnormalities, indicating bone infarcts over the bilateral iliac bones and T-L-spine vertebral bodies, compatible with extensive BMN. The unusual presentation of extensive BMN with severe peripheral cytopenia in the absence of granulomas or pulmonary presentations should alert clinical physicians in epidemic areas. We discuss the use of polymerase chain reaction analysis for TB and magnetic resonance imaging for diagnosis of these patients.

Leukocytosis in polycythemia vera and splenomegaly in essential thrombocythemia are independent risk factors for hemorrhage

Long‐term outcomes are favorable for patients with polycythemia vera (PV) and for patients with essential thrombocythemia (ET). However, hemorrhage is a significant cause of morbidity and mortality in those patients.