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Multiple myeloma (MM) is incurable and the second most common hematologic malignancy in plasma cells. Multiple myeloma stem cell-like cells (MMSCs), a rare population of MM cells, are believed to be the major cause of drug resistance and high recurrence rates in patients with MM. Therefore, developing novel strategies to eradicate MMSCs may favor myeloma treatment. In this study, based on the drug repositioning strategy, we found that albendazole (ABZ), a broad-spectrum antiparasitic drug, selectively suppresses the proliferation of multiple myeloma cells in vitro and in vivo and decreases number of aldehyde dehydrogenase (ALDH)-positive MMSCs in MM. Furthermore, RNA-seq of MM cells after ABZ treatment revealed that inhibition of the nuclear factor kappa-B (NF-κB) pathway is a key mediator of ABZ against MM. Moreover, we demonstrated that ABZ can resensitize cells resistant to bortezomib and overcome MMSCs-induced bortezomib resistance by decreasing ALDH1+ MMSCs numbers. Our findings provide preclinical evidence for utilizing the previously known pharmacologically active drug albendazole for the treatment of multiple myeloma.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by microvascular platelet deposition and thrombus formation with resulting microangiopathic hemolytic anemia. Deficiency of the von Willebrand factor cleavage protease, also known as ADAMTS 13, has been implicated as an important etiological factor in TTP. Little studies were obtained on Chinese patients with TTP until now. Our aim was to analyze the clinical features, outcome and laboratory characteristics of Chinese TTP patients, and determine whether plasma ADAMTS 13 activity is decreased in TTP and its diagnostic value for TTP. Forty-two TTP patients (29 females; 13 males) admitted to our hospital from 1998 to 2010 were analyzed. There were 34 patients (81%) with the triad of TTP, including hemolytic anemia, thrombocytopenia and neurologic abnormalities; 7 (16.7%) had the classical pentad of TTP. Major etiologic factors were acquired autoimmunological abnormalities (31%); no familial TTP was identified in this series. The schistocytes of peripheral blood smears were present in all cases with a mean frequency of 4.6% (range from 0.3% to 13.4%). Plasma ADAMTS 13 activity was determined in 22 patients with the FRET-vWF86 assay. Only 4 idiopathic TTP patients (18.2%) had severe ADAMTS 13 deficiency (activity10%); 9 (40.9%) had moderate decrease of ADAMTS 13 activity (activity: 10-40%); another 9 (40.91%) had normal ADAMTS 13 activity (40%). T lymphocyte subpopulation was measured in 23 TTP patients with FACS Calibur; 14 of the 23 (60.9%) had significantly decreased CD4 cells count and CD4/CD8 ratio, suggesting cellular immune dysfunction may be involved in the pathogenesis of TTP. In the studies, plasmapheresis is the main therapeutic method. 26 of 31 patients (83.9%) accepting plasmapheresis achieved complete remission; those patients who only underwent plasma infusion had low remission rate (18.2%) and high mortality (9/11; 81.8%). Four patients with packed RBC infusion manifested transient exacerbation of neurologic or psychiatric symptoms. In conclusion, the diagnosis of TTP in China is still based on clinical features including evidence of microangiopathic hemolysis. Severe ADAMTS 13 activity deficiency might be a valuable indicator for idiopathic TTP diagnosis. Further studies are needed to determine the real value of ADAMTS 13 activity for TTP diagnosis and whether T lymphocytes subset dysregulation plays important role in TTP pathogenesis.

Objective To evaluate the clinical efficacy and safety of arsenic trioxide, retinoic acid and thalidomide combination therapy in higher risk MDS. Methods Twenty-one patients diagnosed with higher risk MDS were administered 10 mg/day arsenic trioxide intravenously for 10 days, 40 mg/day retinoic acid orally for 2 weeks and 100 mg/day thalidomide orally for 4 weeks per cycle. Results After at least two treatment cycles, 10 patients showed hematologic responses. One achieved CR, one achieved PR, three patients achieved major hematological improvements. The efficacy rate was 24% (5/21), and the response rate was 48% (10/21). The schedule was tolerated well by all patients and toxicities were moderate and reversible. Conclusion The combination of arsenic trioxide, retinoic acid and thalidomide could have therapeutic benefit in higher risk MDS with safety.

A rare case of a 46-year-old man who underwent myelodysplastic syndrome, acute monocytic leukemia with FLT3-ITD mutation and splenic disruption following orthotopic liver transplantation is reported. The study of this case may be helpful to understand both the pathogenesis of acute leukemia and new complication of liver transplantation.

Characterization of an acquired factor VIII inhibitor and plasmapheresis therapy in a patient with bullous pemphigoid

Chemotherapy resistance is still the main clinical limitation to the successful treatment of leukemia. The underlying mechanisms of drug resistance are not fully understood. Recently, research on m...

In the present study, 90 patients with newly diagnosed acute promyelocytic leukemia (APL) were studied for all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3) combination treatment in remission induction and postremission therapy. In addition, 20 APL patients who had achieved complete remission (CR) with an ATRA-based regimen received ATRA/As2O3 combination for consolidation and maintenance were also enrolled. The results showed that ATRA/As2O3 combination therapy yielded a high CR rate of 93.3% and a significantly shorter time to enter CR (median: 31 days; range: 18–59 days) compared to the ATRA-based regimen (n = 72; median: 39 days; range: 25–62 days). With the ATRA/As2O3 combination for CR maintaining, regardless of the way by which CR was attained, the relapse-free survival was significantly better than with an ATRA plus cytotoxic chemotherapy regimen (92.9 ± 3.2% vs. 72.4 ± 7.6%, for the 3-year Kaplan-Meier estimate of relapse-free survival). The drug toxicity profile showed that with the use of As2O3, the incidence of hepatotoxicity was obviously high during remission induction but decreased significantly during postremission treatment. We conclude that APL patients may benefit from the early use of the combination of ATRA and As2O3, in either remission induction or consolidation/maintenance.

Dear Editor, We present here a case of thyroid diffuse large B cell lymphoma (DLBCL) arising on the background of thyroid medullary cancer, which was treated with thyroid lobectomy 10 years ago, and highlight its excellent response to treatment with rituximab-based CHOP chemotherapy (RCHOP). To our knowledge, this is the first case of primary thyroid lymphoma following thyroid medullary cancer. A 63-year-old Chinese womanwas admitted to our hospital with the complaints of neck mass, slight cough and dyspnea for 2 weeks in Aug 2005. She had a previous history of thyroid mass in the right lobe and received lobectomy 10 years ago. At that time, histopathological examination of the biopsy specimen from the thyroid mass was reported as thyroid medullary cancer (Fig. 1a). Immunohistochemical and special stainings displayed Cal (+), CK (+), Syn (+), TG (−), EMA (−), Congo red (+) and NSE (+) (Fig. 1b), which were consistent with the diagnostic features of thyroid medullary cancer. She had not undergone any chemotherapy or radiotherapy, and kept in a good condition after the surgical operation. Regular examinations including thyroid function tests and ultrasonic scan for thyroid showed no abnormality. Two weeks before admission, she found a mass up to 6 cm in diameter in the thyroid, with slight cough and dyspnea. Physical examination showed III grade enlargement in thyroid with deviation of trachea. No lymphadenopathy and hepatosplenomegaly was found. Laboratory examinations revealed that, blood cell counts, urine routine, stool routine, serum electrolytes, liver function, and renal function were within normal limits; serum lactate dehydrogenase (LDH) was 360 u/L, serum β2-microglobulin (BMG), immunoglobulin, and calcitonin were normal. Thyroid functional profile included a T3 of 0.89 nmol/L (0.7–2.7), T4 of 73.6 nmol/L (58.1–164.8), FT3 of 1.80 pmol/L (2.1– 6.2), FrT4 of 13.7 pmol/L (9.0–23.9), TSH of 3.8 mIU/L (0.35–5.5). The anti-microsomal antibody (MCA) and thyroglobulin antibody (TGA) were detected as negative titers with a radio-immunity (RI) method. Bone marrow smear showed normal cellular morphology and cellular ratio. A computerized tomography (CT) scan of the neck showed a mass in thyroid with trachea compressed. Chest and abdomen CT showed no lymph node or organ involvement. With the dyspnea progressed, a tracheal intubation subsequently a surgical operation was performed. The surgery was palliative just for relieving the airway obstruction and mass biopsy. Histopathological examination from thyroid mass biopsy showed diffuse proliferation of lymphoma cells with large nuclei (Fig. 2a). Immunohistochemically staining indicated MUM1(−), CD45R0(−), EMA(−), LCK(−), CaL(−), TG(−), LCA(++), Bcl-6(+), CD10 (+), and CD20(++) (Fig. 2b). A diagnosis of diffuse large B cell lymphoma (DLBCL), stage IE, was made. The international prognostic index (IPI) portrayed a lowintermediate risk. The patient was treated with CHOP (cyclophosphamide, doxorubicin, vincristin, and prednisolone) combined with rituximab (MabThera). After six courses of R-CHOP regimen, the mass in thyroid completely disappeared and she is still in complete remission after a 34 month follow-up. Non-Hodgkin’s lymphoma (NHL) of the thyroid gland is uncommon, accounting for only 1–5% of all thyroid malignancies, and classified as non-epithelial thyroid tumors [1–3]. In this report, we present the case that developed a DLBCL in the thyroid site where a thyroid Ann Hematol (2009) 88:701–702 DOI 10.1007/s00277-008-0639-9