Baijun Fang

Favorable Response of Chronic Refractory Immune Thrombocytopenic Purpura to Mesenchymal Stem Cells

Seven patients with chronic refractory immune thrombocytopenic purpura (ITP) received adipose tissue-derived mesenchymal stem cells (AMSC) from haplo-identical family donors. The AMSC dose was 2.0×10(6)/kg. No side effects were noted after the AMSC infusions. Overall responses were reached in all patients and sustained response rate was 57.1% (4/7). The serum levels of transforming growth factor β1 (TGF-β1), interleukin (IL)-4, and IL-10 were significantly elevated, whereas those of interferon-γ (IFN-γ) and IL-2 were significantly decreased after AMSC administration, compared with those in the patients with active ITP. During follow-up, the cytokine profiles in patients maintaining sustained response remained stable compared with the post-treatment level, but IFN-γ and IL-2 levels were significantly increased, and those of TGF-β1, IL-4, and IL-10 were significantly reduced again in relapsed patients. AMSC therapy seems to represent reasonable salvage treatment in severe, chronic refractory ITP by causing a shift in the Th1/Th2 cytokine balance to the same levels as normal controls.

Improved outcome of adults with aplastic anaemia treated with arsenic trioxide plus ciclosporin.

ECOG/MRC Intergroup Study E2993. Leukemia, 11, 1887–1890. Pardee, T.S., Zuber, J. & Lowe, S.W. (2011) Flt3ITD alters chemotherapy response in vitro and in vivo in a p53-dependent manner. Experimental Hematology, 39, 473–485. Patel, J.P., Gönen, M., Figueroa, M.E., Fernandez, H., Sun, Z., Racevskis, J., Van Vlierberghe, P., Dolgalev, I., Thomas, S., Aminova, O., Huberman, K., Cheng, J., Viale, A., Socci, N.D., Heguy, A., Cherry, A., Vance, G., Higgins, R.R., Ketterling, R.P., Gallagher, R.E., Litzow, M., van den Brink, M.R., Lazarus, H.M., Rowe, J.M., Luger, S., Ferrando, A., Paietta, E., Tallman, M.S., Melnick, A., AbdelWahab, O., & Levine, R.L. (2012) Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. The New England Journal of Medicine, 366, 1–11. Ramanathan, M., Zhou, Z., Cerny, J., Raffel, G. D., Petrillo-Deluca, L., Walsh, W.V., Bathini, V., Vail, M., Smethers, K., Woda, B., Miron, P., Rosmarin, A.G. & Nath, R. (2010) High Complete Remission (CR) Rates and Reduced Early Mortality with High Dose Ara-c (HiDAC) and Mitoxantrone (MITO) Induction Chemotherapy for Older (age>60) High Risk Patients with Acute Myeloid Leukemia (AML). Blood (ASH Annual Meeting Abstracts), 116, 3290. Saito, Y., Kitamura, H., Hijikata, A., TomizawaMurasawa, M., Tanaka, S., Takagi, S., Uchida, N., Suzuki, N., Sone, A., Najima, Y., Ozawa, H., Wake, A., Taniguchi, S., Shultz, L.D., Ohara, O. & Ishikawa, F. (2010) Identification of therapeutic targets for quiescent, chemotherapy-resistant human leukemia stem cells. Science translational medicine, 2, 17ra9. Terwijn, M., Feller, N., Van Rhenen, A., Kelder, A., Westra, G., Zweegman, S., Ossenkoppele, G. & Schuurhuis, G.J. (2009) Interleukin-2 receptor alpha-chain (CD25) expression on leukaemic blasts is predictive for outcome and level of residual disease in AML. European Journal of Cancer, 45, 1692–1699.

Arsenic trioxide improves hematopoiesis in refractory severe aplastic anemia

We investigated the efficacy of arsenic trioxide (ATO) in patients with refractory severe aplastic anemia (SAA). A total of 5 consecutive adults were enrolled. The patients received ATO at a dose of 0.15 mg/kg intravenously daily for 5 days every week for 8 weeks. If necessary, a second course was performed after an interval of one week. All patients achieved clinically significant responses to ATO. The overall complete response rate and overall response rate at 17 weeks were 60% (3/5) and 100%(5/5), respectively. So treatment with ATO may be a feasible approach in patients with refractory SAA.

Arsenic trioxide for refractory aplastic anemia.

Dear Editor, In October 2011, a 23-year-old man was referred to our department. The patient was diagnosed with aplastic anemia in May 2007 due to absolute neutrophil count (ANC) of 0.7 ×10/L, absolute reticulocyte count (ARC) of 21×10/L, hemoglobin of 76 g/L, platelets of 15×10/L, negative Ham test, normal karyotype, and a hypocellular marrow with no excess blasts. On admission, his blood count showed the following values: ANC 0.18×10/L, ARC 13×10/L, hemoglobin 46 g/L, and platelets 5×10/L. Coombs and Ham tests were both negative. Fanconi anemia was also excluded by the chromosomal fragility test. Bone marrow aspirate and biopsy showed hypocellular with no blasts or dysplastic cells. The karyotype was normal. A diagnosis of severe aplastic anemia (SAA) was made. Since 2007, two courses of anti-thymocyte globulin (ATG)/cyclosporine-based regimens were given. He failed the first immunosuppression course (horse ATG + cyclosporine) but showed a satisfied response to the second immunosuppression course (rabbit ATG + cyclosporine). After that, he was transfusion-independent and in good condition for more than 3 years. On readmission in October 2011, the patient was started on cyclosporine (3 mg/kg/day; serum trough level 130–200 ng/mL). No response was observed 2 months later. Afterward, he refused further medications. In May 2012, after informed consent, he was administered with arsenic trioxide (ATO) at a dose of 0.15 mg/kg intravenously daily for 5 days every week. The time to initial response was 38 days. Ten weeks after ATO, his blood count had normalized, and he had remained transfusion-independent. Serial bone marrow biopsies showed hematopoietic recovery accompanied by a decrease in adipocyte number in bone marrow (Fig. 1). The ATO was given for a total of 14 weeks. No obvious ATO-related toxicities were observed. The fact that immunotherapy proves effective in the majority of SAA patients supports the assumption that patients with SAA must have residual hematopoietic progenitors in their bone marrow. SAA is characterized by a reduced number of hematopoietic cells and adipocyte replacement in the bone marrow. Studies suggest that bone marrow adipocytes are predominantly negative regulators of the bone marrow microenvironment [1]. In addition, the data show that ablation of the bone marrow adipocyte compartment can induce osteogenesis [1], which promotes a more supportive environment for hematopoietic reconstitution [1, 2]. This is in accordance with the data that surgical removal of the adipocyte-rich marrow induces hematopoietic infiltration and new osteoid and trabecular bone formation in rabbit tibias [3]. Considering that adipocytes and osteoblasts originate from the common precursors, termed Quande Lin and Yongping Song are equal contributors.

Imatinib plus Granulocyte Colony-Stimulating Factor in Chronic Myeloid Leukemia Patients Who Have Achieved Partial or Complete Cytogenetic Response while on Imatinib

Background: The BCR/ABL tyrosine kinase inhibitor imatinib is highly effective in the treatment of chronic myeloid leukemia (CML) but fails to eliminate all leukemia cells. In this study, we investigated whether the addition of granulocyte colony-stimulating factor (G-CSF) could reduce the level of residual disease in patients with Ph-positive CML who appeared to have achieved a suboptimal response to imatinib alone. Methods: Eleven patients with CML who had achieved ≧35% Ph-negativity on imatinib were enrolled. The starting dose of imatinib was 400 mg or 600 mg orally daily, and of G-CSF 5 µg/kg s.c. daily. The administration of G-CSF was postponed or interrupted in the event of leukocytosis (≧30 ×109 leukocytes/l) until the white blood cell count fell below 20 × 109/l. Efficacy was assessed by serial monitoring of blood levels of BCR-ABL transcripts. Results: Of 11 evaluable patients, 9 had an appreciable decline in BCR-ABL transcript levels; in 7 cases the reduction was greater than 1 log. Conclusions: We conclude that the addition of G-CSF should be considered for patients on imatinib who fail to obtain optimal response to imatinib alone and that this approach deserves further evaluation as frontline therapy for newly diagnosed CML.Baijun Fang and Ling Mai are equal contributors.

Clinical observation of recombinant human endostatin in treating relapsed refractory multiple myeloma

Recombinant human endostatin (rhES) can inhibit multiple myeloma, while its clinical efficacy in treating relapsed refractory multiple myeloma (RRMM) has not been assessed. One hundred and eleven RRMM patients were treated with four different regimens: combination of VD (velcade+dexamethasone) and rhES (n = 25), Thalidomide (Tha) and VD (VTD, n = 22) combination, rhES and conventional chemotherapy combination (n = 32), and combination of conventional chemotherapy and Tha (n = 32). Significant differences were found in progression‐free survival (PFS) between rhES combination groups and conventional chemotherapy combination groups. No statistical difference was found in overall response rate, overall survival or incidences of adverse effects. The combination of rhES with VD or conventional chemotherapy is active in patients with RRMM and prolongs the PFS to improve the quality of life.

Efficacy and safety of G-CSF, low-dose cytarabine and aclarubicin in combination with l -asparaginase, prednisone in the treatment of refractory or relapsed acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) patients who fail to acquire complete remission (CR) or who relapse after initial response have poor prognosis. At present there is no consensus as to the standard salvage therapy for these patients. In this study, we retrospectively evaluate safety and efficacy of a salvage regimen (CAGLP) consisting of G-CSF, low-dose cytarabine, aclarubicin, l-asparaginase and prednisone. Thirty-six patients were included with primary refractory (n=13) or relapse (n=23). The overall response rate (ORR) and CR rate were 86.1% and 63.9%, respectively. With a median follow-up of 34 months, the probability of overall survival (OS) at 2 years was 30%±10% and the disease-free survival (DFS) rate was 15%±8%. Treatment-related mortality was 5.6%. Our preliminary results indicated that CAGLP was feasible, safe and effective as a salvage reinduction chemotherapy for primary refractory and relapsed ALL patients.