Journal of Hematology & Oncology - Latest Articles

Analysis of Ggamma-158(C->T) polymorphism in hemoglobin E/beta-thalassemia major in Southern China

Rong Liu — 2010-09-07T00:00:00Z

Background: The Ggamma-158(C->T) polymorphism plays an important role in the clinical variability of HbE/beta-thalassemia. There is little known about Ggamma-158(C->T) polymorphism in HbE/beta-thalassemia major in southern China. This study aimed to explore the association between HbE/beta-thalassemia major and this polymorphism in southern China.Methods and ResultsThe frequency of the Ggamma-158(C->T) polymorphism has been evaluated in 32 patients with HbE/beta-thalassemia major from southern China. Further analysis of the Ggamma-158(C->T) polymorphism revealed the prominent frequency of this polymorphic pattern among HbE/beta-thalassemia major patients (65.63%). The presence of this polymorphism was strongly correlated with the increase of HbF synthesis. Conclusions: The frequency of the Ggamma-158(C->T) polymorphism was relatively high in southern Chinese patients with HbE/beta-thalassemia major, often accompanying high production of HbF. This feature appears to be different with reports in other races and regions.

Basic Mechanisms of Arsenic Trioxide (ATO)-Induced Apoptosis in Human Leukemia (HL-60) Cells

Clement Yedjou — 2010-08-26T00:00:00Z

Background: Acute promyelocytic leukemia (APL) is a blood cancer that affects people of all ages and strikes about 1,500 patients in the United States each year. The standard treatment of APL has been based on the combined administration of all-trans retinoic acid and chemotherapy including anthracyclins and cytarabine. However, 10-20% of patients relapse, with their disease becoming resistant to conventional treatment. Recently the Food and Drug Administration has approved the use of arsenic trioxide (ATO) or Trisenox for the treatment of APL, based on clinical studies showing a complete remission, especially in relapsed patients. In a recently published study we demonstrated that ATO pharmacology as an anti-cancer drug is associated with its cytotoxic and genotoxic effects in human leukemia cells. Methods: In the present study, we further investigated the apoptotic mechanisms of ATO toxicity using the HL60 cell line as a test model. Apoptosis was measured by flow cytometry analysis of phosphatidylserine externalization and caspase 3 activity, and by DNA laddering assay. Results: Flow cytometry data showed a strong dose-response relationship between ATO exposure and Annexin-V positive HL-60 cells. Similarly, a statistically significant and dose-dependent increase (p<0.05) was recorded with regard to caspase 3 activity in HL-60 cells undergoing late apoptosis. These results were confirmed by data of DNA laddering assay showing a clear evidence of nucleosomal DNA fragmentation in ATO-treated cells. Conclusion: Taken together, our research demonstrated that ATO represents an apoptosis-inducing agent and its apoptotic mechanisms involve phosphatidylserine externalization, caspase 3 activation and nucleosomal DNA fragmentation.

Hodgkin lymphoma treatment with ABVD in the US and the EU: neutropenia occurrence and impaired chemotherapy delivery

Matthias Schwenkglenks — 2010-08-19T00:00:00Z

Background: In newly diagnosed patients with Hodgkin lymphoma (HL) the effect of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD)-related neutropenia on chemotherapy delivery is poorly documented. The aim of this analysis was to assess the impact of chemotherapy-induced neutropenia (CIN) on ABVD chemotherapy delivery in HL patients.Study designData from two similarly designed, prospective, observational studies conducted in the US and the EU were analysed. One hundred and fifteen HL patients who started a new course of ABVD during 2002-2005 were included. The primary objective was to document the effect of neutropenic complications on delivery of ABVD chemotherapy in HL patients. Secondary objectives were to investigate the incidence of CIN and febrile neutropenia (FN) and to compare US and EU practice with ABVD therapy in HL. Pooled data were analysed to explore univariate associations with neutropenic events. Results: Chemotherapy delivery was suboptimal (with a relative dose intensity ≤ 85%) in 18-22% of patients. The incidence of grade 4 CIN in cycles 1-4 was lower in US patients (US 24% vs. EU 32%). Patients in both the US and the EU experienced similar rates of FN across cycles 1-4 (US 12% vs. EU 11%). Use of primary colony-stimulating factor (CSF) prophylaxis and of any CSF was more common in the US than the EU (37% vs. 4% and 78% vs. 38%, respectively). The relative risk (RR) of dose delays was 1.54 (95% confidence interval [CI] 1.08-2.23, p = 0.036) for patients with vs. without grade 4 CIN and the RR of grade 4 CIN was 0.35 (95% CI 0.12-1.06, p = 0.046) for patients with vs. without primary CSF prophylaxis. Conclusions: In this population of HL patients, CIN was frequent and FN occurrence clinically relevant. Chemotherapy delivery was suboptimal. CSF prophylaxis appeared to reduce CIN rates.

Angiogenesis inhibitors in the treatment of prostate cancer

Clara Hwang — 2010-08-02T00:00:00Z

Prostate cancer remains a significant public health problem, with limited therapeutic options in the setting of castrate-resistant metastatic disease. Angiogenesis inhibition is a relatively novel antineoplastic approach, which targets the reliance of tumor growth on the formation of new blood vessels. This strategy has been used successfully in other solid tumor types, with the FDA approval of anti-angiogenic agents in breast, lung, colon, brain, and kidney cancer. The application of anti-angiogenic therapy to prostate cancer is reviewed in this article, with attention to efficacy and toxicity results from several classes of anti-angiogenic agents. Ultimately, the fate of anti-angiogenic agents in prostate cancer rests on the eagerly anticipated results of several key phase III studies.

Ring chromosome 18 abnormality in acute myelogenous leukemia: the clinical dilemma

Shanthi Sivendran — 2010-07-22T00:00:00Z

The ring chromosome is a circular, structural abnormality composed of either multiple chromosomes or a single chromosome with loss of genetic material at one or both ends. This chromosomal rearrangement is often unstable with frequent recombinations and may be accompanied by either loss or amplification of genetic material 1 . Considering that ring chromosomes are rare in acute myelogenous leukemia (AML), it is difficult to risk stratify patient prognosis, particularly when the ring chromosome occurs as the sole abnormality. Here we report a case of a ring chromosome 18 abnormality in a patient with newly diagnosed AML with monocytic differentiation. Cytogenetic analysis demonstrated 46, XY, r(18)(p11q21) karyotype in 19 of 34 evaluated metaphase cells. The patient received induction chemotherapy and subsequent allogeneic cord blood transplant from a sex-matched donor, and remained in hematologic and cytogenetic remission for 120 days post transplant. Soon after, he developed post transplant lymphoproliferative disorder and died of multi-organ failure. Although r(18) chromosomal abnormalities were not classified in the recent updated evidence-and expert opinion-based recommendations for the diagnosis and management of AML (likely due to the small number of reported cases), the patient was treated as high risk with stem cell transplantation. This was based on the unstable nature of the ring chromosome and the poor outcomes described in the literature of patients with sole ring 18 abnormalities.

Pancytopenia associated with clonazepam

Marnelli Bautista-Quach — 2010-07-14T00:00:00Z

We report a case of a 48-year-old Chinese female with end-stage renal disease and chronic anemia on hemodialysis. Clonazepam was prescribed for myoclonus disorder two weeks prior to her hospitalization. Subsequently, she was hospitalized for neutropenic fever with thrombocytopenia and worsening anemia. Bone marrow examination demonstrated a markedly hypocellular marrow (10-20% total cellularity). Clonazepam was discontinued, with gradual improvement of thrombocytopenia, and neutropenia in 1-2 weeks. To our knowledge, this is the first reported case of pancytopenia associated with clonazepam. We recommend patients taking clonazepam to be monitored with regular complete blood count to check for clinically significant pancytopenia or thrombocytopenia.

Management of stage one and two-E gastric large B-cell lymphoma: chemotherapy alone or surgery followed by chemotherapy?

Yassir Sbitti — 2010-06-22T00:00:00Z

Management of localized primary gastric B lymphoma (PGL) remains controversial. The aim of this study is to compare two treatments: chemotherapy alone and surgery plus chemotherapy.MaterialsRecords of all patients with a diagnosis of gastric lymphoma and which were treated in the National Institute of Oncology, between 1999 and 2006, were reviewed and patients fulfilling the following criteria were included in this study: histologically proven large-cell B lymphoma of the stomach; complete clinical information stage I/II disease according to the Musshoff staging; patients who received surgery followed by chemotherapy (group I) or chemotherapy alone (group II). Results: This study included 82 patients who were treated for cancer in our Institute. All clinical and pathological features were similar between the two groups, except that patients of group-I had significantly more stage II disease (P = 0.023) than that of group II. Among the 52 patients who could be evaluated for response to chemotherapy, there were 45 who had complete response to treatment, 3 had partial response to the treatment and 4 had progressive disease. The projected 5-year relapse-free survival (RFS) and overall survival (OS) of group I were 86.69% (95% CI, 57.9 - 97.7%) and 90.0% (95% CI, 58.0 - 97.8%), respectively. And the projected 5-year relapse-free survival RFS and OS of group II were 86.67% (95% CI, 57.0 - 88.2%) and 93.33% (95% CI, 73.3 - 98.7%) respectively. There were no statistically significant differences in RFS (P = 0.485) and OS (P = 0.551) between the two groups. Conclusion: Our data suggest that chemotherapy alone may be a reasonable alternative treatment for stage I/II gastric large-cell lymphoma but this result must be confirmed by prospective randomized clinical trials.

CyberKnife enhanced conventionally fractionated chemoradiation for high grade glioma in close proximity to critical structures

Eric Oermann — 2010-06-09T00:00:00Z

IntroductionWith conventional radiation technique alone, it is difficult to deliver radical treatment (≥ 60 Gy) to gliomas that are close to critical structures without incurring the risk of late radiation induced complications. Temozolomide-related improvements in high-grade glioma survival have placed a higher premium on optimal radiation therapy delivery. We investigated the safety and efficacy of utilizing highly conformal and precise CyberKnife radiotherapy to enhance conventional radiotherapy in the treatment of high grade glioma. Methods: Between January 2002 and January 2009, 24 patients with good performance status and high-grade gliomas in close proximity to critical structures (i.e. eyes, optic nerves, optic chiasm and brainstem) were treated with the CyberKnife. All patients received conventional radiation therapy following tumor resection, with a median dose of 50 Gy (range: 40 - 50.4 Gy). Subsequently, an additional dose of 10 Gy was delivered in 5 successive 2 Gy daily fractions utilizing the CyberKnife® image-guided radiosurgical system. The majority of patients (88%) received concurrent and/or adjuvant Temozolmide. Results: During CyberKnife treatments, the mean number of radiation beams utilized was 173 and the mean number of verification images was 58. Among the 24 patients, the mean clinical treatment volume was 174 cc, the mean prescription isodose line was 73% and the mean percent target coverage was 94%. At a median follow-up of 23 months for the glioblastoma multiforme cohort, the median survival was 18 months and the two-year survival rate was 37%. At a median follow-up of 63 months for the anaplastic glioma cohort, the median survival has not been reached and the 4-year survival rate was 71%. There have been no severe late complications referable to this radiation regimen in these patients. Conclusion: We utilized fractionated CyberKnife radiotherapy as an adjunct to conventional radiation to improve the targeting accuracy of high-grade glioma radiation treatment. This technique was safe, effective and allowed for optimal dose-delivery in our patients. The value of image-guided radiation therapy for the treatment of high-grade gliomas deserves further study.

An epidemiological investigation of leukemia incidence between 2003 and 2007 in Nanjing, China

Bao-An Chen — 2010-06-02T00:00:00Z

Background: There has been little literature about leukemia epidemiology in Nanjing in recent years. We aimed to explore the incidence rate, gender and age distribution of leukemia in Nanjing using the leukemia database of the city. Results: The average yearly incidence rate of leukemia was 3.68/105 during 2003 - 2007 in Nanjing. There were no significant difference in gender (x 2 = 3.266, p > 0.05) or seasons (x 2 = 11.36, p > 0.05). The incidence rate was the highest in group aged 80~ years (18.64/105). AML accounted for approximately 36.8% of all leukemias. Conclusions: The incidence rate of leukemia, especially in the aged population, was relatively high in Nanjing. Leukemia is the major malignant tumor in children. Therefore, more attention should be paid to leukemia in children and the aged people.

Lenalidomide induced good clinical response in a patient with multiple relapsed and refractory Hodgkin's lymphoma

Inga Mandac — 2010-05-28T00:00:00Z

Background: A 24-year-old female patient was diagnosed with classic Hodgkin's lymphoma in clinical stage II, and combination chemotherapy followed by radiotherapy was initiated. During the following 5 years, the disease progressed despite several standard therapeutic approaches, including autologous and allogeneic stem cell transplantation. Methods: Lenalidomide (25 mg daily) treatment was then initiated in a continuous dosing schedule. Positron emission tomography scans were performed before and during lenalidomide treatment. Hematologic and laboratory values, as well as physical condition were also assessed before and during lenalidomide treatment. Results: Four months after continuous lenalidomide treatment, tumor load was significantly reduced, B symptoms had resolved, and the patient's physical condition had improved, allowing her to resume normal daily-living activities. Evaluations after 15 months of lenalidomide treatment indicated limited disease progression. Nevertheless, the patient was feeling well and maintaining a normal active life. Treatment was well tolerated, allowing the patient to remain on continuous dosing, which has now been maintained for 18 months. Conclusion: Daily, long-term lenalidomide treatment provided clinical benefit and was well tolerated in a patient with relapsed, advanced classic Hodgkin's lymphoma.