Pharmacodynamic effects of adjunctive high dose atorvastatin on double dose clopidogrel in patients with high on-treatment platelet reactivity depending on diabetes mellitus status

Diabetes mellitus (DM) is associated with impaired platelet response to clopidogrel. In patients with high on-treatment platelet reactivity (HTPR) while on standard-dose clopidogrel, high-dose atorvastatin enhances the pharmacodynamic (PD) effects of double-dose clopidogrel. It is unknown if similar effects are achieved in patients with DM. This study compare the PD effects of high-dose atorvastatin associated with double dose clopidogrel in HTPR patients with and without DM undergoing elective percutaneous coronary intervention (PCI). This is a post hoc analysis of a prospective randomized PD study that compared double-dose (150 mg) clopidogrel associated with high-dose (80 mg) atorvastatin to double-dose clopidogrel alone in statin naïve patients with HTPR undergoing elective PCI. In this analysis, patients were divided in two groups according to DM (n = 27) and non-DM (n = 49) status. Platelet reactivity was evaluated immediately before PCI and at 30 days using the VerifyNow P2Y12 assay. HTPR was defined as P2Y12 reaction units (PRU) ≥235. Administering high-dose atorvastatin in addition to high-dose clipodogrel, the 30 days absolute PRU changes (106 ± 75 vs 100 ± 42, p = 0.7) and optimal response rates (83 vs 84 %; p = 0.9) were similar in DM and non-DM patients. The baseline variables significantly associated with 30-day optimal response to high-dose clopidogrel were: atorvastatin treatment (OR = 7.5 [95 % CI 1.19–47]; p = 0.032) in DM patients; PRU values (OR = 0.9 [95 % CI 0.95–0.99]; p = 0.031) and creatinine clearance (OR = 1.07 [95 % CI 1.008–1.13]; p = 0.025) in non-DM patients. High-dose atorvastatin significantly improved the PD effects of double-dose clopidogrel in DM patients with HTPR undergoing elective PCI.     

High-dose chemotherapy and autologous stem-cell transplantation in Korean patients with relapsed or refractory Hodgkin lymphoma

High-dose chemotherapy and autologous stem-cell transplantation (HDCT–ASCT) is a standard therapy for patients with relapsed or refractory Hodgkin lymphoma (HL). However, its efficacy in Asian patients has not been well investigated. A retrospective analysis of outcomes in 10 consecutive patients who underwent ASCT for HL in a single Korean centre from August 2005 to September 2010 was conducted. The median age was 34.5 years (range 17–64 years) and seven patients were male. Six patients were of stage III–IV at presentation. B symptoms were present in six patients. International Prognostic Score (IPS) was as follows: IPS = 1 (n = 5), IPS = 2 (n = 1), IPS = 4 (n = 2), and IPS = 5 (n = 2). The analysis included nine patients with relapsed HL and one primary refractory case. Four patients were in second complete response and the others were in partial response after salvage chemotherapy. With a median follow-up duration of 58.0 months, 3-year progression-free survival rate and overall survival rate from ASCT were 40 and 76 %, respectively. The results suggest that the efficacy of high-dose chemotherapy followed by ASCT in Korean patients with refractory or relapsed HL is comparable to that in Western patients.     

Successful mobilization of peripheral blood stem cells in heavily pretreated myeloma patients with G-CSF alone

 We investigated the feasibility of mobilizing peripheral blood stem cells (PBSC) with G-CSF alone in 24 patients with multiple myeloma. The median age was 53 years (range 33–62). All patients had stage II/III disease and responded to standard first-line (n=6) or salvage chemotherapy (n=18). The median number of previous chemotherapy cycles was 7 (4–18) and the median number of prior melphalan-cycles was 6 (0–14). Nine (35%) patients had experienced prior radiation therapy. The patients received either 10 μg/kg G-CSF (n=18) or 24 μg/kg G-CSF (n=7, including one patient with previous 10 μg/kg G-CSF stimulation) daily s.c. for 5 or more consecutive days until completion of harvesting, starting apheresis on the fifth day. G-CSF treatment was well tolerated, with only slight bone pain in half of the patients (51%). After a median of three (range 1–7) apheresis procedures, medians of 3.8 (0.3–17)×10⁶ CD34+ cells/kg, 8.5 (4.5–24)×10⁸ MNC/kg, 2.9 (0.6–39.4)×10⁴ CFU-GM/kg, and 5.6 (0.9–49)×10⁴ BFU-E/kg were harvested. Three patients (12%) with extensive melphalan pretreatment failed the target collection of at least 2.0×10⁶ CD34+ cell/kg. Pretreatment with six or more cycles of melphalan yielded a smaller number of CD34+ cells than pretreatment with fewer than six cycles (2.5 vs 5.3×10⁶/kg;p=0.001). Nineteen patients underwent high-dose chemotherapy consisting of either total marrow irradiation (9 Gy)/busulfan (12 mg/kg) and cyclophosphamide (120 mg/kg) (n=10), or busulfan (14 mg/kg)/cyclophosphamide (120 mg/kg) (n=5), or tandem melphalan (200 mg/m²). The median time for granulocyte (>1.0/nl) and platelet (>50/nl) recovery was 10 and 14 days (ranges 7–12 and 8–40), respectively. G-CSF alone is a safe, alternative approach to mobilizing sufficient PBSC in patients with multiple myeloma and allows an exact prediction of harvest time. G-CSF-mobilized PBSCs ensure rapid engraftment after myeloablative therapy. Melphalan treatment should be avoided in patients who are candidates for high-dose chemotherapy. Received: February 5, 1998 / Accepted: April 14, 1998     

Efficacy and safety of autologous hematopoietic cell transplantation in elderly patients with multiple myeloma: a retrospective national multi-site cohort study

We aimed to test the efficacy and toxicity of autologous hematopoietic cell transplant (HCT) in Multiple Myeloma (MM) patients aged ≥65 years compared to patients aged 60–64. Two hundred twenty consecutive patients (age ≥65, n = 87) with MM aged 60 and above, who underwent HCT as part of an upfront MM treatment, at four Israeli centers between 2000 and 2014 were included. A melphalan dose of 200 mg/m² was more frequent in the 60–64 age group vs. the ≥65 age group (77 vs. 57%, p = 0.002). There were no differences between groups in median day of neutrophil engraftment, incidence of infections, grades 3–4 mucositis, cardiovascular events, or non-relapse mortality at 100 days post HCT (4.7, vs. 5%, p = 0.9). A similar rate of improvement in response level was observed (36, vs. 35%, p = 0.87). At 3 years post HCT progression-free survival (PFS) was higher in the 60–64 age group (42 vs. 29%, p = 0.04); however, it was no longer so after adjustment for disease status prior to HCT (p = 0.49). In a Multivariate analysis, melphalan doses and age did not predict PFS. There was no difference in overall survival (OS) between age groups (p = 0.2). We conclude that toxicity profile, response, PFS, and OS of HCT in aged ≥65 patients with myeloma is similar to patients aged 60–64.     

Salvage treatment with upfront melphalan 100 mg/m2 and consolidation with novel drugs for fulminant progression of multiple myeloma

Patients (pts) with fulminant progression (FPG) of multiple myeloma (MM) after autologous stem cell transplantation (ASCT) have poor prognosis. Pancytopenia, extramedullary disease, and/or renal impairment are often present, and treatment options are limited. We have retrospectively evaluated 31 pts with FPG of MM after ASCT who were treated upfront salvage therapy with melphalan 100 mg/m² (MEL 100) followed by PBSC support and consolidation therapy using regimens containing thalidomide (n?=?16) or bortezomib (n?=?15). The overall response rate (ORR) was 58% (18/31). After MEL 100, one patient achieved complete remission (3%), 26% of pts very good partial remission, 29% of pts partial remission, and 42% of pts stable disease. Progression within 3 months after MEL 100 occurred in 35% of pts. The median follow-up from MEL 100 was 8 months. The median TTP was 5 months (range, 2–15 months), and the median OS was 8 months (range, 3–23 months). There were no treatment-related deaths. In fulminant progression of MM, upfront MEL 100 is a safe salvage regimen with good response rate (ORR, 58%). Treatment with upfront MEL 100 followed by a thalidomide- or bortezomib-based regimen can prolong overall survival to more than 12 months in 33% of pts with fulminant progression of MM.     

Clinical significance of the appearance of abnormal protein band in patients with multiple myeloma

Multiple myeloma (MM) is characterized by clonal expansion of malignant bone marrow cells producing a unique monoclonal immunoglobulin. The appearance of abnormal protein band (APB) in MM has been reported during follow-up. We aimed to evaluate the clinical characteristics and outcomes of patients with APB in a single center cohort. A total of 377 consecutive MM patients were treated at the Asan Medical Center between January 2002 and December 2012. We compared clinical characteristics and survival outcome between those with and without APB. Of the 377 patients, 34 (9 %) experienced APB. They comprised 18.2 % (27/148) of patients treated with autologous stem cell transplantation (ASCT) and 3.1 % (7/229) of those not receiving ASCT. APB occurred after a median of 7.9 months (range, 2.2–95.7 months) from diagnosis. Immunoglobulin isotypes at diagnosis were as follows: IgG (n?=?10), IgA (n?=?8), IgD (n?=?5), free κ (n?=?4), and free λ (n?=?7). Nine patients experienced a second APB. With a median follow-up of 54.1 months, the median overall survival (OS) has not been reached in patients with APB and was 38.3 months in patients without (P?<?0.001). Multivariate analysis indicated that the development of APB was a significant favorable prognostic factor for OS (hazard ratio 0.21; 95 % confidence interval 0.08–0.52). Serum β₂-microglobulin, albumin, creatinine, and ASCT were also independent prognostic factors for OS. Further investigation is required to establish the mechanisms underlying APB in MM.     

Peripheral blood stem cell collection in elderly patients

Intensive treatments like autologous blood stem cell transplantations are standard consolidation treatments for lymphoma and myeloma in young people. The upper age limit for these procedures is constantly increasing. Instead of studying the impact of aging on harvesting peripheral blood stem cells (PBSC), we performed a retrospective study to explore the feasibility of collecting stem cells from patients older than 65 years and compared the efficacy to harvest in younger patients. During a period of 7 years, we identified 108 patients with myeloma or lymphoma who were older than 65 years who underwent PBSC collection. Only eight patients failed to produce a successful harvest. The majority of patients only needed one apheresis (71%). There was a median number of 5.3?×?10⁶ CD34+ cells/kg. Our study demonstrated that older patients can also undergo PBSC harvests similar to younger patients.     

Epidemiology and treatment outcome of invasive fungal infections in patients with hematological malignancies

Invasive fungal infection (IFI) causes morbidity and mortality among patients with hematological malignancies who receive cytotoxic chemotherapy or hematopoietic stem cell transplantation (HSCT). We evaluated the incidence and treatment outcomes of proven and probable IFI in 22 institutions between 2006 and 2008 following the recent European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) consensus criteria. We analyzed 2,821 patients with hematological malignancies, including 597 who had undergone HSCT; these included patients with acute leukemia (n = 697), myelodysplastic syndrome (n = 284), lymphoma (n = 1465), or multiple myeloma (n = 375). IFIs were diagnosed in 38 (1.3%) patients (18 proven and 20 probable), including 20 patients who underwent HSCT and 18 who received chemotherapy alone; these included patients with aspergillosis (n = 23), candidiasis (n = 6), mucormycosis (n = 6), trichosporonosis (n = 2), and geotrichosis (n = 1). The incidence of IFI was 5.4 % in allogeneic HSCT patients, 0.4 % in autologous HSCT patients, and 0.8 % in patients receiving chemotherapy alone. Eighteen patients with aspergillosis were diagnosed with probable pulmonary IFI as determined by computed tomography scan and positive galactomannan assay. Overall, antifungal targeted therapies resulted in successful outcomes in 60.0 % of patients. IFI-attributable mortality rate was higher in HSCT patients than in those receiving chemotherapy alone, but the difference was not statistically significant.     

Bendamustine in combination with thalidomide and dexamethasone is a viable salvage option in myeloma relapsed and/or refractory to bortezomib and lenalidomide

Treatment options are limited in myeloma relapsed or refractory to both bortezomib and lenalidomide (double-relapsed/refractory multiple myeloma; DRMM). Bendamustine is an antitumour agent that has efficacy in relapsed myeloma. We retrospectively analysed data from 30 DRMM patients who received a combination of bendamustine, thalidomide and dexamethasone (BTD) in 28-day treatment cycles. Bendamustine was administered with a cumulative dose of up to 200 mg/m². Thalidomide (50–150 mg) was given daily as tolerated, and dexamethasone was given at an equivalent dose of up to 160 mg per cycle. A median of 5 (2–9) treatment cycles were administered per patient. Twenty-six patients (87 %) achieved stable disease or better. At a median follow-up time of 12.1 (2.3–21.5) months, median (95 % CI) progression-free survival and overall survival were 4.0 (2.6–5.3) months and 7.2 (5.2–9.2) months, respectively. The most common grade 3–4 adverse events were haematological: anaemia (n?=?8, 34.8 %), neutropenia (n?=?16, 69.6 %) and thrombocytopenia (n?=?10, 43.5 %). Non-haematological toxicities included pain (n?=?3, 13.0 %), infection (n?=?7, 30.4 %) and sensory neuropathy (n?=?1, 4.3 %). We propose that BTD is a viable salvage treatment option for DRMM patients.     

Similar survival outcomes in patients with biclonal versus monoclonal myeloma: a multi-institutional matched case-control study

Multiple myeloma is a plasma cell malignancy characterized by clonal proliferation of plasma cells in the bone marrow and associated organ damage. Usually, patients with myeloma present with a single monoclonal protein in serum and/or urine constituted by one heavy chain and one light chain. In less than 5% of the patients, more than one monoclonal protein can be identified. The aim of our retrospective multicenter matched case-control study was to describe the characteristics of cases with biclonal myeloma and compare them against a control group of monoclonal myeloma patients matched by age, sex, and year of diagnosis. A total of 50 previously untreated cases with biclonal myeloma and 50 matched controls with monoclonal myeloma were included in this study. The controls were matched (1:1) for age, sex, year of diagnosis, and participating center. There were no differences in the rates of anemia (52 vs. 59%; p = 0.52), renal dysfunction (36 vs. 34%; p = 0.83), hypercalcemia (9 vs. 16%; p = 0.28), or presence of lytic lesions (23 vs. 16%; p = 0.38) between groups. Similarly, there was no difference in the rates of overall response to therapy (85 vs. 90%; p = 0.88) or survival rates of cases with biclonal myeloma and controls with monoclonal myeloma (4-year survival 72 vs. 76%; p = 0.23). Results of our study suggest that patients with biclonal myeloma have similar response and survival rates than patients with monoclonal myeloma.     

Efficacy and toxicity of Trastuzumab and Paclitaxel plus Capecitabine in the first-line treatment of HER2-positive metastatic breast cancer

Purpose

Combinations of trastuzumab with paclitaxel or capecitabine are effective therapies in human epidermal growth factor 2 (HER2)-positive metastatic breast cancer (MBC). This retrospective study evaluated the efficacy and toxicity of trastuzumab and paclitaxel plus capecitabine in the first-line therapy for patients with HER2-positive MBC.

Methods

A total of 40 patients with HER2-positive MBC treated between January 2008 and January 2011 were evaluated retrospectively in 6 institutions. Three patients with performance score of 3 who died before response assessment were excluded from the study. The patients were given trastuzumab 8 mg/kg loading dose followed by then 6 mg/kg dose on day 1 and paclitaxel 175 mg/m² on day 1 plus capecitabine 825 mg/m² twice daily on days 1–14 every 3 weeks.

Results

A total of 287 cycles of chemotherapy were administered with a median of 8 treatment cycles per patient (range 3–12). Median follow-up period was 24.7 months (range 4.7–51). There were 9 patients (24.3 %) with complete responses, 21 (56.8 %) with partial responses, 4 (10.8 %) with stable disease and 3 (8.1 %) with progressive disease resulting in an overall response rate (ORR) of 81.1 %. Median progression-free survival and overall survival were 14 and 38.4 months, respectively. Rates of grade 3 adverse events were neutropenia (n = 4, 10.8 %), cardiac dysfunction (n = 1, 2.7 %), hand-foot syndrome (n = 2, 5.4 %), nausea (n = 2, 5.4 %), vomiting (n = 2, 5.4 %), fatigue (n = 1, 2.7 %), diarrhea (n = 1, 2.7 %), neuropathy (n = 1, 2.7 %) and alopecia (n = 1, 2.7 %).

Conclusions

Combination of trastuzumab and paclitaxel plus capecitabine is an effective and well-tolerated regimen in the first-line therapy for women with HER2-positive MBC.     

Efficacy of stem cell mobilization in patients with newly diagnosed multiple myeloma after a CTD (cyclophosphamide, thalidomide, and dexamethasone) regimen

The CTD (cyclophosphamide, thalidomide, and dexamethasone) regimen is known to be an effective primary therapy in patients with newly diagnosed multiple myeloma (MM). However, stem cell yields after CTD remain inconsistent. The aim of the present study is to identify the influence of the CTD regimen on the outcome of peripheral blood stem cell (PBSC) collection. Fifty-four patients received four cycles of CTD, and PBSCs were mobilized with cyclophosphamide and G-CSF or with G-CSF alone. Each patient from whom ≤4.0 × 10⁶ CD34⁺ cells/kg were collected received a second mobilization course. The median duration from the start of a CTD regimen to the first collection was 4.3 months. Forty-eight patients were mobilized with cyclophosphamide followed by G-CSF, and six patients were mobilized with G-CSF alone. The median day of apheresis was day 3 (range day 2–day 5). The overall response rate at mobilization was 96.3 %, including 11.1 % complete response, 22.2 % very good partial response, and 63.0 % partial response. The median number of harvested CD34⁺ cells was 12.8 × 10⁶ cells/kg. At the second mobilization, 88.9 % of patients reached the minimal stem cell collection target of ≥2.0 × 10⁶ cells/kg, and 75.9 % of patients achieved the collection target of ≥4.0 × 10⁶ cells/kg. CTD within four cycles is an effective primary therapy in patients with newly diagnosed MM and only minimally affects subsequent PBSC collection.     

Therapeutic Plasma Exchange in Patients with Neurologic Disorders: Review of 63 Cases

Therapeutic plasma exchange (TPE) is a procedure that reduces circulating autoantibodies of the patients. TPE is commonly used in neurological disorders where autoimmunity plays a major role. We report our experience with regard to the indications, adverse events and outcomes of plasma exchange in neurological disorders. Sixty-three patients were included to this retrospective study. Median age was 48 years (range 1–85), there was a predominance of males. Neurological indications included Guillain-Barrè syndrome (n = 22), myasthenia gravis (n = 21), chronic inflammatory demyelinating polyneuropathy (n = 7), polymyositis (n = 3), multifocal motor neuropathy (n = 2), acute disseminated encephalomyelitis (n = 2), neuromyelitis optica (n = 2), multiple sclerosis (n = 2), limbic encephalitis (n = 1) and transverse myelitis (n = 1). TPE was frontline therapy in 57 % of the patients (n = 36). Total number of TPE sessions was 517; median number of sessions per patient was 8 (range 1–66). TPE was done through a central venous access in 97 % and through a peripheral venous access in 3 % of the patients. Human albumin was used as replacement fluid in 49 %, hydroxyethyl starch (HES) in 49 % and fresh frozen plasma in 2 % of the cases. Adverse reactions were recorded in 60 % of the patients. Total ratio of complications in 517 TPE procedures was 10.8 % and these were mild and manageable such as allergic reactions and hypotension. Overall response rate was 81 %. Interestingly, complication and response rates were similar in both HES and human albumin groups. We conclude that TPE is an effective treatment in neurologic diseases in which autoimmunity plays an important role in the pathogenesis and HES can be used instead of albumin as replacement fluid in these disorders, since it is cost-effective, has similar efficacy and complication rates.     

Imatinib in myeloid/lymphoid neoplasms with eosinophilia and rearrangement of <Emphasis Type="Italic">PDGFRB</Emphasis> in chronic or blast phase

We evaluated clinical characteristics and outcome on imatinib of 22 patients with myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRB. Median age was 49 years (range 20–80), 91% were male. Fifteen different PDGFRB fusion genes were identified. Eosinophilia was absent in 4/19 (21%) cases and only 11/19 (58%) cases had eosinophils ≥1.5×10⁹/L. On imatinib, 17/17 (100%) patients in chronic phase achieved complete hematologic remission after median 2 months (range 0–13)?. Complete cytogenetic remission and/or complete molecular remission by RT-PCR were achieved in 12/13 (92%) and 12/14 patients (86%) after median 10 (range 3–34) and 19 months (range 7–110), respectively. In patients with blast phase (myeloid, n = 2; lymphoid, n = 3), treatment included combinations of imatinib (n = 5), intensive chemotherapy (n = 3), and/or allogeneic stem cell transplantation (n = 3). All 3 transplanted patients (complex karyotype, n = 2) experienced early relapse. Initially, patients were treated with imatinib 400 mg/day (n = 15) or 100 mg/day (n = 7), the dose was reduced from 400 mg/day to 100 mg/day during follow-up in 9 patients. After a median treatment of 71 months (range 1–135), the 5-year survival rate was 83%; 4/22 (18%) patients died (chronic phase; n = 2; blast phase, n = 2) due to progression (n = 3) or comorbidity while in remission (n = 1). Of note, 3/4 patients had a complex karyotype. In summary, the most important characteristics of myeloid/lymphoid neoplasms with rearrangement of PDGFRB include (a) male predominance, (b) frequent lack of hypereosinophilia, (c) presentation in chronic or blast phase, (d) rapid responses and long-term remission on low-dose imatinib, and (e) possible adverse prognostic impact of a complex karyotype.     

Bevacizumab plus irinotecan in recurrent or progressive malign glioma: a multicenter study of the Anatolian Society of Medical Oncology (ASMO)

Purposes

The overall prognosis for recurrent malignant glioma (MG) is extremely poor, and treatment options are limited. We evaluated our multicenter retrospective experience for patients with recurrent MG administering bevacizumab and irinotecan in combination therapy.

Methods

A total of 115 patients with grade IV glial tumor (n = 93) and grade III glial tumor (n = 22) were retrospectively evaluated at 14 centers in Turkey. Primary objectives of the study were to evaluate the efficacy and toxicity of the bevacizumab and irinotecan as salvage treatment based on response to therapy, progression-free survival (PFS), 6 months of PFS, overall survival (OS), and 6 months of OS (OS6).

Results

Bevacizumab and irinotecan were performed as second line (79.1 %) and third line treatment (20.9 %). Median chemotherapy cycle was 6 (range 1–37), and median follow-up was 6 months (range 1–36 months). Objective response rate was 39.1 %. Six-month PFS and OS6 were 46.3 % and 67.5 %, respectively. Median PFS was 6 months (95 % CI 2.5–9.5) and 6 months (95 % CI 4.9–7.1) in the grade III and IV groups, respectively (p = 0.773). Median OS was 9 months (95 % CI 7.1–10.9) and 8 months (95 % CI 6.6–9.4) in the grade III and IV groups, respectively (p = 0.450). Serious toxicities were observed in 7.8 % of patients. Treatment-related toxic death was observed in 3 patients. There was no treatment related to central nervous system hemorrhage or other serious hemorrhages.

Conclusions

Present study results were consistent with previous studies. In addition, we detected similar outcomes in grade III and IV glial tumors.     

Immunoglobulin subtypes predict therapy response to the biologics in patients with rheumatoid arthritis

To analyze the effectiveness of rituximab (RTX) versus alternative TNF antagonists (aTNFs) on rheumatoid arthritis (RA) disease activity in different subgroups of patients and relation with extraarticular manifestations of RA and to assess that RF-subsets have potential as predictors of clinical response to RTX. Patients with RA (n = 40, M/F: 3/37) who received aTNFs at least 6 months with good response (group I; n = 20) or discontinued at least one aTNFs because of the ineffectiveness and subsequently received RTX at least one course (group II; n = 20) were retrospectively evaluated. IgM-, IgA-, IgG-rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) levels were measured by ELISA technique. Extraarticular manifestations and radiological scores were also recorded. The mean (SD) age was 51.7 ± 6.5 years in group I and 52.1 ± 6.1 years in group II patients (p > 0.05). The median disease durations were higher in group II than group I [8.0 (2–30) vs. 13 (3–35) years, respectively, p = 0.04]. Presence of RF [13(61.9 %) vs. 20(100 %) p = 0.001] and extraarticular involvement [5(25 %) vs. 13(65 %) p = 0.01] were higher in group II patients. When Ig-RF subgroups analyzed, all subgroup (IgA, IgM, IgG) levels were higher in group II (p = 0.001, p = 0.05, p = 0.001). IgA-RF levels were significantly high in patients with extraarticular involvement (p = 0.04). Association between high RF levels and having extraarticular manifestations in RA patients may largely be attributed to the IgA isotype.     

High-dose imatinib versus high-dose imatinib in combination with intermediate-dose cytarabine in patients with first chronic phase myeloid leukemia: a randomized phase III trial of the Dutch-Belgian HOVON study group

Despite the revolutionary change in the prognosis of chronic myeloid leukemia (CML) patients with the introduction of imatinib, patients with resistant disease still pose a considerable problem. In this multicenter, randomized phase III trial, we investigate whether the combination of high-dose imatinib and intermediate-dose cytarabine compared to high-dose imatinib alone, improves the rate of major molecular response (MMR) in newly diagnosed CML patients. This study was closed prematurely because of declining inclusion due to the introduction of second generation tyrosine kinase inhibitors and only one third of the initially required patients were accrued. One hundred nine patients aged 18–65 years were randomly assigned to either imatinib 800 mg (n?=?55) or to imatinib 800 mg in combination with two successive cycles of cytarabine 200 mg/m² for 7 days (n?=?54). After a median follow-up of 41 months, 67 % of patients were still on protocol treatment. The MMR rate at 12 months was 56 % in the imatinib arm and 48 % in the combination arm (p?=?0.39). Progression-free survival was 96 % after 1 year and 89 % after 4 years. Four-year overall survival was 97 %. Adverse events grades 3 and 4 were more common in the combination arm. The addition of intermediate-dose of cytarabine to imatinib did not improve the MMR rate at 12 months. However, the underpowering of the study precludes any definitive conclusions. This trial is registered at www.trialregister.nl (NTR674).     

Efficacy of preoperative endoscopic nasobiliary drainage for hilar cholangiocarcinoma

Background/Purpose

Although percutaneous transhepatic biliary drainage has previously been recommended as a primary preoperative step, endoscopic nasobiliary drainage (ENBD) is prevalent as an alternative procedure. Few reports assess the efficacy and safety of ENBD in a substantial patient cohort.

Methods

Of 116 patients with hilar cholangiocarcinoma who underwent surgery, 62 (43 men and 19 women, median age 69 years) underwent preoperative ENBD. After classification of lesions according to Bismuth–Corlette (B–C) criteria, we evaluated efficacy and safety with respect to B–C type.

Results

Patients were classified as B–C types I (n = 5), II (n = 21), IIIa (n = 23), IIIb (n = 5), and IV (n = 8). Preoperative single ENBD was effective in 46/62 patients (74%) including 5/5 (100%) B–C type I, 20/21 (94%) type II, 16/23 (70%) type IIIa, 4/5 (80%) type IIIb, and 1/8 (13%) type IV. Sixteen cases (26%) required additional drainages with ENBD or endoscopic biliary stenting (EBS) in 8/16 (50%), and with PTBD in 8/16 (50%). Mild acute pancreatitis (n = 1, 2%), segmental cholangitis (n = 2, 3%), and acute cholangitis with catheter obstruction (n = 7, 11%) occurred with ENBD.

Conclusions

Preoperative single ENBD in the future remnant lobe is effective treatment for B–C type I–III hilar cholangiocarcimona. Preoperative ENBD was rarely complicated with segmental cholangitis.     

Favorable outcomes of intravenous busulfan, fludarabine, and 400 cGy total body irradiation-based reduced-intensity conditioning allogeneic stem cell transplantation for acute myelogenous leukemia with old age and/or co-morbidities

Traditional transplant conditioning regimens have a limiting factor regarding co-morbidities or old age. Therefore, reduced-intensity conditioning (RIC) regimens have been increasingly used. To define the role of RIC in AML with old age (≥55 years) and/or co-morbidities (HCT-CI scores ≥2), we analyzed patients who received allogeneic stem cell transplantation (SCT) with Flu/Bu/TBI 400 cGy/±antithymocyte globulin (ATG) conditioning regimen. Seventeen men and 15 women were enrolled. The median age was 45 years (range 17–65 years). All patients were in first (n = 25) or second (n = 7) complete remission before undergoing allogeneic SCT. Patients were transplanted from HLA-mismatched unrelated donors (n = 5), matched unrelated donors (n = 10), and matched sibling (n = 17). Calcineurin inhibitor and a short course of standard dose methotrexate were used to prevent graft-versus-host disease (GVHD). All patients achieved engraftment. At a median follow-up of 18 months (range 4–40) for survivors, the estimated 2-year rates of overall survival, event-free survival, transplantation-related mortality, and relapse were 66, 63, 26, and 16%, respectively. The incidence of acute (grades II–IV) and chronic GVHD by NIH consensus criteria was 34.4 and 62.5%. This study suggests that the Flu/Bu/TBI 400 cGy or Flu/Bu/TBI 400 cGy/ATG-based conditioning regimens maybe a feasible therapeutic approach for AML with old age and/or co-morbidities.     

Changes in treatment of rectal cancer: increased use of low anterior resection

Purpose

The most common surgical procedures for patients with rectal cancer are low anterior resection (LAR) or abdominoperineal excision (APE). The aim of the present study is to evaluate and report the changes in the incidence of LAR and APE in the surgical treatment of rectal cancer over the last 15 years in a single surgical department.

Methods

The patient sample consisted of 251 consecutive patients (mean age 65.17; age range 22–87) that underwent surgical treatment for rectal cancer in a single center from 1996 to 2010. This time frame was divided into three 5-year periods (1996–2000, 2001–2005 and 2006–2010). Patients were classified into one of the aforementioned groups, depending on the date of their treatment.

Results

In the first period (1996–2000), 71 patients were treated for rectal cancer. Among them, 32.4% (n = 23) underwent an abdominoperineal excision (APE) while 56.3% (n = 40) were treated with LAR. In the second period (2001–2005), included 102 patients, from which 29.4% (n = 30) received an APE and 60.8% (n = 62) underwent a LAR for their disease. In the final period (2006–2010), from the 78 patients, only 12.8% (n = 10) of them underwent APE, while 74.3% (n = 58) were treated with LAR. There was a statistically significant (chi-square test, P = 0.005) difference between the 3 periods of time concerning the performance of LAR and APE.

Conclusions

According to the results of the present study, the rates of APE seem to decrease during the last 15 years, while LAR is more widely used in the surgical treatment of rectal cancer.