Advances in the biosynthesis of pentostatin / 生物工程学报

Pentostatin is a nucleoside antibiotics with a strong inhibitory effect on adenosine deaminase, and is widely used in the clinical treatment of malignant tumors. However, the high cost hampers its application. In the past 10 years, the biosynthesis of pentostatin were focused on strain breeding, optimization of medium composition and fermentation process. To date, there are no reviews summarizing the elucidated biosynthetic mechanism of pentostatin. This review starts by introducing the various chemical route for production of pentostatin, followed by summarizing the mechanisms of pentostatin biosynthesis in different microorganisms. Finally, challenges for biosynthesis of pentostatin were discussed, and strategies for regulating and improving the microbial synthesis of pentostatin were proposed.

Fludarabine and Rituximab in Relapsed or Refractory Hairy Cell Leukmia Variant: A Case Report and Review of Literature / 고신대학교의과대학학술지

Hairy cell leukemia (HCL) is a rare chronic B cell leukemia morphologically characterized by cells with an abundant cytoplasm and hair-like projections that can be found in the peripheral blood and bone marrow. The treatment for HCL is splenectomy or chemotherapy with the purine analogs pentostatin and cladribine. However, patients continue to relapse. Retreatment with the same or alternate purine analogs produces lower response rates and a shorter duration of response. Fludarabine is another purine analog widely used in treating indolent lymphoid cancers, often in combination with rituximab. Here, we report a case of HCL variant in a 60-year-old man who experienced multiple relapses after splenectomy and retreatment with cladribine. The patient was then treated with fludarabine and rituximab combination chemotherapy. After the treatment, he achieved complete remission that continued for 35 months.

Chronic Lymphocytic Leukemia-Era of Targeted Therapy / 대한내과학회지

Chronic lymphocytic leukemia (CLL) is a unique indolent B-cell leukemia which is rare in Korea. Many patients with early stage CLL do not require immediate treatment, while those with advanced stage or symptoms need systemic chemotherapy. As our understanding about the pathophysiology of CLL increases, significant advances have been achieved in the treatment of this disease. Modern molecular genetics have been revealing remarkable heterogeneity of various genetic alterations and the corresponding prognostic stratification in CLL. The treatment of CLL had been developed from nitrogen mustard alkylating agent like chlorambucil to combination therapy including purine analogues like pentostatin and fludarabine until early 2000s. Since the introduction of targeted agent like anti-CD20 and anti-CD52 monoclonal antibodies in the treatment of CLL, the treatment outcome of CLL has leaped further. In conclusion, one of the current standard regimens in patients with untreated CLL is the combination of rituximab, cyclophosphamide and fludarabine. We recently passed the entrance for the era of targeted therapy, and are exploring various new agents and their combinations.

A Case of Steroid Refractory Acute GVHD Treated with IL-2 & TNF-alpha Blocker in a Myelodysplastic Syndrome Patient who Underwent Unrelated Allogeneic Stem Cell Transplantation

Hematopoietic stem cell transplantation has evolved as a central treatment modality for the management of various hematologic malignancies. Despite adequate posttransplantation immunosuppressive therapy, acute GVHD remains a major cause of morbidity and mortality, even for the patients who have received HLA identical sibling grafts. Once established, acute GVHD is difficult to treat, and the best primary treatments such as corticosteroid have shown responses of approximately 50%. Once GVHD becomes steroid-refractory, the chances of survival are slim at best, and the possibility of long-term complications from chronic GVHD is almost always the rule. Many agents are currently being evaluated to treat this malady, including ATG, monoclonal antibodies, pentostatin, denileukin diftitox, etc. We reported here on a case of steroid refractory acute GVHD that was treated with IL-2 and TNF-alpha blocker in myelodysplastic syndrome patient who underwent unrelated allogeneic stem cell transplantation.

Report of 3 Cases of Hairy Cell Leukemia Treated with 2-Chlorodeoxyadenosine / 대한혈액학회지

Hairy cell leukemia (HCL) is an uncommon chronic B-cell lymphoproliferative disorder characterized by cytopenia, splenomegaly and mononuclear cells displaying cytoplasmic projections. Diagnosis is based on the distinctive hairy cell morphology and immunological profile. In the last 10 to 15 years the prognosis of patients with HCL has improved considerably following the use of purine analogues such as deoxycoformycin and 2-chlorodeoxyadenosine (2-CdA). We report 3 patients with HCL who were treated with 2-CdA at a daily dosage of 0.1mg/kg by continuous intravenous infusion for 7 days. After 1 or 2 courses of treatment, all patients achieved complete remission and are still alive in disease-free status.