Entezam Sahovic

Activity of azacitidine in chronic myelomonocytic leukemia

Hypomethylating drugs are useful in the management of myelodysplastic syndrome (MDS). Two of these drugs, azacitidine and decitabine, have received FDA approval for the treatment of MDS and chronic myelomonocytic leukemia (CMML). However, phase 2 and 3 studies that assessed these agents in MDS included only a small number of patients with CMML. The objective of this study was to evaluate the efficacy and safety of azacitidine in the treatment of CMML.

Bortezomib, dexamethasone, cyclophosphamide and lenalidomide combination for newly diagnosed multiple myeloma: phase 1 results from the multicenter EVOLUTION study

This phase 1 study (Clinicaltrials.gov: NCT00507442) was conducted to determine the maximum tolerated dose (MTD) of cyclophosphamide in combination with bortezomib, dexamethasone and lenalidomide (VDCR) and to assess the safety and efficacy of this combination in untreated multiple myeloma patients. Cohorts of three to six patients received a cyclophosphamide dosage of 100, 200, 300, 400 or 500 mg/m2 (on days 1 and 8) plus bortezomib 1.3 mg/m2 (on days 1, 4, 8 and 11), dexamethasone 40 mg (on days 1, 8 and 15) and lenalidomide 15 mg (on days 1–14), for eight 21-day induction cycles, followed by four 42-day maintenance cycles (bortezomib 1.3 mg/m2, on days 1, 8, 15 and 22). The MTD was the cyclophosphamide dose below which more than one of six patients experienced a dose-limiting toxicity (DLT). Twenty-five patients were treated. Two DLTs were seen, of grade 4 febrile neutropenia (cyclophosphamide 400 mg/m2) and grade 4 herpes zoster despite anti-viral prophylaxis (cyclophosphamide 500 mg/m2). No cumulative hematological toxicity or thromboembolic episodes were reported. The overall response rate was 96%, including 20% stringent complete response (CR), 40% CR/near-complete response and 68% ⩾very good partial response. VDCR is well tolerated and highly active in this population. No MTD was reached; the recommended phase 2 cyclophosphamide dose in VDCR is 500 mg/m2, which was the highest dose tested.

Allogeneic stem cell transplantation for acute myeloid leukemia with del(7q) following untreated chronic lymphocytic leukemia

The development of hematologic malignancy in the presence of chronic lymphocytic leukemia (CLL) is rare. We present a case of acute myeloid leukemia (AML) with del(7q) occurring in a patient with a 4-year history of untreated CLL. Application of flow cytometry and immunohistochemistry allowed for characterization of two distinct coexisting malignant cell populations. After undergoing induction and consolidation chemotherapy, the patient achieved complete remission of AML with the persistence of CLL. Allogeneic transplantation was pursued given his unfavorable cytogenetics. Subsequent matched unrelated donor allogeneic stem cell transplantation resulted in full engraftment and complete remission, with no evidence of AML or CLL. Due to a scarcity of reported cases, insight into treatment and prognosis in cases of concurrent AML and CLL is limited. However, prognosis seems dependent on the chemosensitivity of AML. CLL did not have a detrimental effect on treatment or transplant outcome in our case. This is the first reported case of concomitant de novo AML and CLL to undergo allogeneic transplantation. The patient remained in complete hematologic and cytogenetic remission of both malignancies over a year after transplantation.

Viability and Potency of Hematopoietic Progenitor Cells after Prolonged Cryopreservation at –80°C

Peripheral blood HPC were collected from 28 donors at our institution between April 1994 and June 2002 using the Baxter CS-3000 blood cell separator. Patient characteristics are shown in table 1 . Only 3 donors of the HPC products were alive at the time of analysis of the products (UPN 947, UPN 1,000 and the normal unrelated donor); the recipient of the unrelated-donor HPC product was deceased at the time of analysis. On the day of the third transplant, the UPN 947 sample was taken directly from the HPC product infused at the bedside. The UPN 1,000 sample was obtained from a remaining unit stored in the same cassette as the infused product and analyzed 231 days after the third transplant. Patients provided inPeripheral blood hematopoietic progenitor cells (HPC) collected by apheresis and cryopreserved constitute the major source of stem cells for autologous transplantation, which is widely used to treat hematological malignancy [1, 2] . Controlled-rate freezing, using dimethyl sulfoxide (DMSO), with or without hydroxyethyl starch (HES) as cryoprotectant, and storage of products in liquid nitrogen (LN) is the most widely used method of cryopreservation and storage of HPC [3, 4] . The method requires specialized equipment, a constant supply of LN and carries the risk of cryogenic injury to laboratory personnel. An alternative method of cryopreservation with 5% DMSO, 6% HES and 4% human serum albumin (HSA) was described by Stiff et al. [5] , utilizing non-controlledrate freezing and storage in a mechanical freezer at –80 ° C. HPC cryopreserved by this method provided sustained engraftment in 68 of 72 patients after high-dose chemotherapy [6] . However, the effect of storage on HPC activity for 1 5 years under these conditions has not been examined. We examined the viability and hematopoietic colony-forming activity of HPC products stored in DMSO/HES/HSA at –80 ° C between 7.1 and 14.9 years. The mean number of days of storage of the HPC product at –80 ° C was 4,254 (range 2,582–5,433, standard deviation 563). Received: November 25, 2010 Accepted after revision: March 10, 2011 Published online: May 17, 2011

Use of octreotide for relief of gastro-intestinal (GI) symptoms in systemic mastocytosis.

e present the case of an 82-year-old Caucasian female who was evaluated by hematology oncology for further work up and management of her chronic but progressive anemia. She reported weight loss, poor appetite, fatigue, nausea, several episodes of non-bloody diarrhea and increased abdominal girth over the past 3 months. On admission, her hemoglobin was 8.9 gm/dL, platelets were 43 k/mcl, WBC was 5.49 K/mcl with absolute neutrophil count of 3.73 k/mcl and 0% peripheral blasts. Her metabolic panel was abnormal for elevated LDH (245 U/L) and alkaline phosphatase (207 U/L). Her liver function tests were normal except for albumin of 2.5 g/dl. Computed tomography (CT) of the abdomen/pelvis showed splenomegaly, ascites, and retroperitoneal lymphadenopathy, a concern for a lymphoproliferative or metastatic disease. A bone marrow biopsy and aspirate performed to determine the cause of her progressive anemia and thrombocytopenia revealed hypercellularity (90%) and increased blasts (35% on the touch preparation). The blasts had scant cytoplasm and fine chromatin (blue arrows in Figure 1). In addition, there were paratrabecular infiltrates of round to spindled mast cells (red arrow in Figure 1), which by immunohistochemistry were strongly positive for tryptase (shown in Figure 2), CD117, CD68 and CD25. The blasts were weakly positive for CD117 and strongly positive for myeloperoxidase, CD56, Bcl-2, and CD43 (not shown). The aspirate was severely hemodiluted, likely due to the reticulin fibrosis observed in the biopsy. Flow cytometry specimen was also hemodiluted (9% blasts) with the following myeloid immunophenotype: CD33 positive CD13 positive CD56 positive CD117 partially positive CD34 negative HLA-DR negative. Based on these findings the patient was diagnosed with AML and SM, a subset of systemic mastocytosis with associated clonal hematologic non-mast cell lineage disease (SM-AHNMD). The patient’s diarrhea responded briefly to antimotility agent loperamide, but while awaiting definitive treatment plan, her symptoms worsened rapidly and required admission for severe, profuse non-bloody diarrhea, dehydration and abdominal distension. Splenomegaly and ascites were noted on clinical exam. Labs continued to show anemia and thrombocytopenia. Initial test was positive for clostridium difficile (C. diff). This was successfully treated with metronidazole and then with oral vancomycin. Subsequent tests for C. diff, other infectious agents and transglutaminase IgA antibody were negative. However, the patient continued to have multiple episodes of diarrhea with little relief from antimotility agents. Diarrhea was deemed secondary to SM. Extensive work up for portal hypertension was non-diagnostic. She could not undergo colonoscopy and liver biopsy due to thrombocytopenia. As a consideration for treatment with imatinib she was tested for BCR/ABL and PDGFRA fusion genes which were negative. KIT mutation analysis could not be performed due to lack of tissue sample. After a lengthy discussion with the patient regarding various options of treatment, she chose palliative care and hospice. However, severe diarrhea limited her transition to hospice; she was then started on a trial of octreotide every 8 h for her diarrhea. She had a rapid response with dra-

A247 Bortezomib, Dexamethasone, Cyclophosphamide, Lenalidomide (VDCR) Has High Efficacy in First-Line MM

A246 VMP Results in Fewer Bone Events and Greater ALP Increases Versus MP in the VISTA Study in Front-Line MM M Delforge,1 M Kropff,1 I Spicka,2 M Petrucci,3 PG Richardson,4 R Schlag,5 N Khuageva,6 MA Dimopoulos,7 O Shpilberg,8 O Samoilova,9 MV Mateos,10 K Liu,11 W Deraedt,12 H van de Velde,13 J San Miguel14 1University of Munster, Germany; 2University Hospital, Prague, Czech Republic; 3University La Sapienza, Rome, Italy; 4Dana-Farber Cancer Institute, Boston, MA; 5Praxisklinik Dr. Schlag, Wurzburg, Germany; 6SP Botkin Moscow City Clinical Hospital, Russian Federation; 7University of Athens, School of Medicine, Athens, Greece; 8Rabin Medical Center, Petah-Tiqva, Israel; 9Nizhnii Novgorod Region Clinical Hospital, Russian Federation; 10Hospital Universitario Salamanca, CIC, IBMCC (USAL-CSIC), Spain; 11Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Raritan; 12Johnson & Johnson Pharmaceutical Research & Development, Beerse, Belgium; 13Johnson & Johnson Pharmaceutical Research & Development, Beerse, Belgium; 14Hospital Universitario Salamanca. CIC, IBMCC (USAL-CSIC), Salamanca, Spain