Kooperativer Bibliotheksverbund

In: Hematological Oncology, Wiley, Vol. 35, No. 4 ( 2017-12), p. 804-809

Abstract: The prognostic role of CD15 in acute myeloid leukemia (AML) has been tested in different studies with conflicting results. To address this issue, we retrospectively evaluated a cohort of 460 AML patients of all ages with the exclusion of acute promyelocytic leukemia (M/F 243/217, median age 50.6 years [range 0.9‐81.2] ) intensively treated at our institute between January 1999 and December 2010. CD15 positivity was found in 171 of 406 evaluable patients (42.1%). Complete remission (CR) was achieved by 334 patients (72.6%), while 82 (17.8%) were resistant and 44 (9.6%) died during induction: the median CR duration was 15.5 months (range 0.6‐176.0), with 2‐year disease‐free survival rate of 45.1% (95% confidence interval 39.6‐50.6). The median overall survival was 14.4 months (range 0.3‐177.0), with 2‐year overall survival rate of 42.2% (95% confidence interval 37.5‐46.9). At univariate analysis for CR achievement, age  〈  60 years ( P   〈  .001), World Health Organization classification ( P  = .045), low‐risk karyotype ( P   〈  .001), no high‐risk karyotype ( P  = .006), positivity for AML‐ETO ( P  = .004)/CBFβ‐MYH11 ( P  = .003)/CD15 ( P  = .006)/CD11b ( P  = .013), negativity for FLT3‐ITD ( P  = .001), Hb  〉  8 g/dL ( P  = .020), and white blood cell  〈  50 × 10 9 /L ( P  = .034) had a favorable impact. At a multivariate logistic regression model, CD15 positivity ( P  = .002), age  〈  60 years ( P  = .008), white blood cell  〈  50 × 10 9 /L ( P  = .017), and low‐risk/no high‐risk karyotype ( P  = .026/ P  = .025) retained an independent prognostic role on CR achievement . The baseline assessment of CD15 positivity appears to have a role in the risk evaluation for CR achievement in AML patients undergoing intensive chemotherapy and should be assessed in prospective studies together with other clinical and biologic features already reported.

Type of Medium: Online Resource

ISSN: 0278-0232 , 1099-1069

URL: Issue

URL: Article

DOI: 10.1002/hon.v35.4

DOI: 10.1002/hon.2331

Language: English

Publisher: Wiley

Publication Date: 2017

detail.hit.zdb_id: 2001443-0

In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 4740-4740

Abstract: Background: Several biological parameters define patients with multiple myeloma (MM) at high-risk of progression or death. The well-known International Staging System (ISS), as well as age per se, are insufficient to explain differences of overall survival (OS) in patients over 65 years, who are 2/3 of newly diagnosed (ND) MM patients. We have recently showed that a frailty score combining age, functional status (Activity of Daily Living and Instrumental Activity of Daily living scores) and comorbidities (Charlson index) defines 3 categories of patients - fit, intermediate-fitness, frail - with significantly differences in OS and progression-free survival (Larocca A, et al. Blood 2013 122:687). Here we assess the causes of the different mortality in intermediate-fitness and frail groups compared to fit ones and present a final prognostic score based on the combination of ISS and frailty scores. Methods: NDMM patients over 65 years enrolled in 3 clinical trials, receiving either lenalidomide, bortezomib or carfilzomib were included in the analysis. Details on treatment regimens and results of these studies have previously been reported (Palumbo A, et al. Blood 2013 122:536; Larocca A, et al. Blood 2013 122:539, Bringhen S et al. Blood 2014 Jul 3;124(1):63-9). The cumulative incidences of discontinuation and toxicities were calculated using the Fine & Gray model. The frailty score was combined with ISS with the CHi-squared Automatic Interaction Detector method used as an iterative decision tree. Results: 869 patients (median age 74 years) were included in the analysis; 260 (30%) were frail, 269 (31%) intermediated-fitness and 340 (39%) fit. The 3-year OS was 57% in frail, 76% in intermediated-fitness and 84% in fit patients. Overall, 143 patients (16%) died, 70 (27%) frail, 39 (14%) intermediate-fitness and 34 (10%) fit. The causes of death were: disease progression [35 (13%) in frail, 22 (8%) in intermediate-fitness and 18 (5%) in fit patients] and toxicity [21 (8%), 10 (4%) and 11 (3%), respectively] . The higher risk of death for progression was related with the lower dose-intensity due to the higher rate of drug discontinuation and/or dose reduction. The average dose intensity was lower in frail (74%, p=0.0006) and intermediate-fitness patients (80%, p=0.07) compared with fit patients (85%). The cumulative incidence of drug discontinuation for any cause, excluding progression and death, was higher in frail (25%; HR 2.21, p 〈 0.001) and intermediate-fitness (22%; HR: 1.41, p=0.052) patients compared with fit ones (17%). The most frequent reasons for toxicity-related death were cardiac events [11 (4%) in frail patients, 2 (1%) in intermediate-fitness, 3 (1%) in fit] and infections [8 (3%), 2 (1%) and 2 (1%), respectively] . When we combined the frailty score with the ISS, 6 groups of patients and 4 risk categories were identified: fit patients with ISS I at low risk (15%; 3-year OS: 94%), fit patients with ISS stage II or III and intermediate-fitness patients with ISS I, II or III at intermediate risk (55%; 3-year OS: 75-77%.), frail patients with ISS stage I or II at high risk (19%; 3-year OS: 61%) and frail patients with ISS stage III at very-high risk (11%, 3-year OS: 55%) (Figure 1). Conclusion: The inferior survival observed among intermediate-fitness and in frail patients as compared to fit ones, is related to a higher rate of toxic deaths and disease progression, due to a lower dose intensity. The combination of the frailty score, evaluating the patient's status, and the standard ISS, taking into account the biological characteristics of the disease, can predict survival and enhances the single predictive values of the scores, thus representing a valuable tool for treatment-decision in the clinical practice. Figure 1. Overall survival of patients classified into 6 categories according to the recursive partitioning analysis by combining the frailty score and the International Staging System. Figure 1. Overall survival of patients classified into 6 categories according to the recursive partitioning analysis by combining the frailty score and the International Staging System. Disclosures Larocca: Janssen Cilag: Honoraria; Celgene: Honoraria. Off Label Use: Use off-label of lenalidomide (immunomodulatory drug), carfilzomib (proteasome inhibitor), subcutaneous bortezomib (proteasome inhibitor) in terms of schedule used and combination.. Bringhen:Onyx: Consultancy; Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Janssen and Cilag: Honoraria; Celgene: Honoraria. Hajek:Janssen: Honoraria; Celgene: Consultancy, Honoraria; Merck: Consultancy, Honoraria. Offidani:Celgene: Honoraria; Janssen: Honoraria. Maracci:Mundipharma: Honoraria. Gay:Sanofi: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Marasca:Janssen: Honoraria; Celgene: Honoraria. Giuliani:Celgene: Research Funding. Musto:Janssen: Honoraria; Celgene: Honoraria. Boccadoro:Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sonneveld:Millenium: Honoraria, Research Funding; Onyx: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Palumbo:Celgene: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria; Onyx Pharmaceuticals: Consultancy, Honoraria; Array BioPharma: Honoraria; Amgen: Consultancy, Honoraria; Sanofi: Honoraria; Genmab A/S: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V124.21.4740.4740

Language: English

Publisher: American Society of Hematology

Publication Date: 2014

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: British Journal of Haematology, Wiley, Vol. 172, No. 4 ( 2016-02), p. 554-560

Abstract: This study aimed to review the clinical features and outcome of 53 patients with solitary plasmacytoma managed at our Institution between 1976 and 2012. Thirty‐five patients had bone solitary plasmacytoma and 18 extramedullary solitary plasmacytoma. Tumour sizes were larger in patients with bone involvement ( P  = 0·003). Treatment consisted of local radiotherapy ( n  = 26), radiotherapy + chemotherapy ( n  = 15), surgery ( n  = 4) and chemotherapy ( n  = 8); the local control rate was 94·3%. Progression to multiple myeloma was recorded in 20/35 (57·1%) patients with bone involvement and in 1/18 (5·5%) patients with extramedullary disease ( P  = 0·0003). The 5‐year overall survival ( OS ) rate was 78·4%; bone solitary plasmacytoma patients had a significantly worse OS (71·9% vs. 88·2%, respectively; P  = 0·029) and 5‐year progression‐free survival ( PFS ; 53·0% vs. 88·5%; P  = 0·0003) compared to extramedullary solitary plasmacytoma patients. On univariate analysis, bone disease and size (≥5 cm) impacted negatively on PFS ( P  = 0·0027 and P  = 0·04, respectively). Bone disease also affected OS ( P  = 0·04). In multivariate analysis bone location was the only independent prognostic factor for PFS ( P  = 0·0041) and OS ( P  = 0·021). Patients with bone solitary plasmacytoma have a significantly worse prognosis than extramedullary solitary plasmacytoma cases.

Type of Medium: Online Resource

ISSN: 0007-1048 , 1365-2141

URL: Issue

URL: Article

DOI: 10.1111/bjh.2016.172.issue-4

DOI: 10.1111/bjh.13870

Language: English

Publisher: Wiley

Publication Date: 2016

detail.hit.zdb_id: 1475751-5

In: Annals of Hematology, Springer Science and Business Media LLC, Vol. 94, No. 2 ( 2015-2), p. 195-200

Type of Medium: Online Resource

ISSN: 0939-5555 , 1432-0584

URL: Article

DOI: 10.1007/s00277-014-2197-7

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2015

detail.hit.zdb_id: 1458429-3

In: Leukemia & Lymphoma, Informa UK Limited, Vol. 57, No. 7 ( 2016-07-02), p. 1716-1718

Type of Medium: Online Resource

ISSN: 1042-8194 , 1029-2403

URL: Article

DOI: 10.3109/10428194.2015.1106531

Language: English

Publisher: Informa UK Limited

Publication Date: 2016

detail.hit.zdb_id: 2030637-4

In: Leukemia & Lymphoma, Informa UK Limited, Vol. 56, No. 9 ( 2015-09-02), p. 2743-2746

Type of Medium: Online Resource

ISSN: 1042-8194 , 1029-2403

URL: Article

DOI: 10.3109/10428194.2015.1009059

Language: English

Publisher: Informa UK Limited

Publication Date: 2015

detail.hit.zdb_id: 2030637-4

In: European Journal of Haematology, Wiley, Vol. 98, No. 3 ( 2017-03), p. 242-249

Abstract: To report our experience concerning sustained response ( SR ) after TPO ‐ RA discontinuation in adult pITP patients and to identify possible predictive factors for outcome. Methods Thirty‐nine pITP patients who received a TPO ‐ RA were evaluated. Response (R) was defined as a platelet count ≥30 × 10 9 /L and at least a twofold increase in the baseline count and complete response ( CR ) as a platelet count ≥100 × 10 9 /L, in the absence of bleeding. Durable response ( DR ) was defined as a R/ CR persisting ≥4 wk with a stable dose of TPO ‐ RA , and SR as the first assessed platelet count ≥30 × 10 9 /L, available at more than 4 wk after discontinuation of TPO ‐ RA , in the absence of other concomitant or rescue therapies. Results Twenty‐nine/39 (74%) were responders: 18 (46%) reached a CR and 11 (28%) a R. A DR was observed in 16/29 (55%) responders. Seven SR (18%) were reached: five of seven patients achieved a SR from a prior DR . CR was statistically associated with the achievement of a subsequent DR : 13/18 (72%) CR patients obtained a DR , while only three of 11 (27%) R ones did ( P = 0.027). Conclusions CR was a significant prognostic factor for the achievement of a DR . Moreover, we observed a trend for DR patients to obtain a subsequent SR .

Type of Medium: Online Resource

ISSN: 0902-4441 , 1600-0609

URL: Issue

URL: Article

DOI: 10.1111/ejh.2017.98.issue-3

DOI: 10.1111/ejh.12822

Language: English

Publisher: Wiley

Publication Date: 2017

detail.hit.zdb_id: 2027114-1

In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 5753-5753

Abstract: Background: Bendamustine is effective as first-line treatment of multiple myeloma (MM) patients, as well as in heavily pre-treated relapsed/refractory patients. The combination of bendamustine with new drugs has been investigated in patients who have exhausted other treatment options. Aims: This single arm study was conducted, after the approval of our Ethic’s Committee, to assess the activity and safety of bendamustine and dexamethasone in heavily pre-treated relapsed/refractory MM patients in our Home Care Unit program. Patients and Methods: Between May 2012 and March 2013, 8 relapsed/refractory frail MM patients were treated with bendamustine (60 mg/m2 days 1, 8, 15) and dexamethasone (20 mg days 1, 8, 15, 22) for up to nine 28-day cycles. Based on the frailty of our patient’s population, the use of other new agents was avoided. All patients were followed by our Home Care Unit in view of the advanced stage of the disease and of the patients’ inability to attend our day hospital unit. All patients had received a median of 4 (range 2-6) previous lines of therapy including alkylating and new drugs, such as thalidomide (25%), lenalidomide (100%) and bortezomib (100%). One patient received, as salvage treatment, a second autologous stem cell transplant (ASCT) followed by a sibling allogenic transplantation. Six patients (75%) were refractory to bortezomib and 5 (62,5%) to lenalidomide, 4 (50%) were double refractory. Main pre-treatment characteristics were: median time from diagnosis 82.1 months (range 14.2- 255.6), median age 76 years (range 53-83), ECOG performance status 2-3, median Hb level of 10.5 g/dl (range 9.0-13.0), median platelet count of 227.000/mm3 (range 58.000-378.000); all patient had bone lytic lesions and 1 had an extramedullary plasmacytoma of the right thigh; 1 patient had a moderate renal failure (creatinine clearance 44ml/min). Stable disease (SD) was considered a valid therapeutic goal in this advanced cohort of patients. Results: After a median number of 6 cycles administered (range 1-9), among the 7 patients evaluable for response (1 patient was withdrawn early due to death) 75% achieved a clinical benefit (≥ SD) and in particular: 1 very good partial response (VGPR), 3 partial response (PR), 1 minor response (MR) and 1 SD. The patient with extramedullary plasmacytoma had a PR confirmed by the mass reduction. Four patients had an early discontinuation of treatment due to: infections in 3 cases (2 fatal) and a heart failure, not related to treatment, in 1. The median time to best response was 4 months (range 1-6). Median time to progression was 10.8 months (range 5.0-15.2) and the median progression-free survival (PFS) was 9.1 months (range 0.6-15.2). Infectious complication was the primary and major side effect in 6/8 (75%) patients, two of which of grade 5, one grade 3 and three grade 2 according to CTCAE ver. 4. Myelotoxicity was acceptable: only one grade 3-4 anemia, thrombocytopenia and neutropenia. The other non-hematological side effect was nausea in all patients (grade 2), which resolved with antiemetic prophylaxis. Conclusions: Bendamustine and dexamethasone administered at home has proven effective, with a favorable balance in terms of cost/effectiveness, in our cohort of high risk and advanced MM patients in poor clinical conditions. The response rate and PFS are encouraging in this setting of patients and this approach should be considered as a valid option for relapsed/refractory MM, including patients double refractory to lenalidomide and bortezomib. In view of the acceptable and manageable toxicity, this combination is feasible in the framework of a Home Care Unit program. Disclosures Off Label Use: Use off-label of Bendamustine (alkylating). Petrucci:Celgene: Honoraria; Janssen-Cilag: Honoraria; Sanofi: Honoraria; Bristol Meyer-Sqibb: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V124.21.5753.5753

Language: English

Publisher: American Society of Hematology

Publication Date: 2014

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 3455-3455

Abstract: Background: Solitary plasmacytoma (SP) is a rare form of plasma cell dyscrasia that represents 2.8-5% of all plasma cell disorders. It is characterized by a localized accumulation of neoplastic monoclonal plasma cells, without evidence of systemic disease, such as multiple myeloma (MM). It can be classified into two groups according to the localization: SP of the bone (SBP) and extramedullary plasmacytoma (EMP). The common presentation of the SBP is in the axial skeleton, whereas the EMP is usually seen in the head and neck. The clinical course and prognosis are quite different between these two entities. Here we present the clinical features, treatment strategies and relative prognostic factors of a series of SP patients followed at a single center over four decades. Methods: A retrospective study was carried out in 53 patients with SP referred at our Institution between 1976 and 2012. Patients’ characteristics are shown in Table 1. The median follow-up was 8.9 years (range 0.5-38.1). Thirty-five patients had SBP and 18 patients EMP. The median age was 56.8 years (range 27-80). The male to female ratio was 1.18:1 and 2.6:1 in SBP and EMP, respectively. The vertebral column (48% of cases) and the upper respiratory tract (50% of cases) were the most common sites of involvement SBP and EMP, respectively. Serum M-protein was detected in 62.8% and 27.7% of the SBP and EMP cases (P=0.0156). The tumor sizes were larger in the SBP group than in the EMP group (P=0.0039). Treatment consisted of local radiotherapy (n=26), combined radiotherapy + chemotherapy (n=15), surgery alone (n=4) and chemotherapy alone (n=8). The radiation dose was available for 35 patients and the median radiation dose administered was 41 Gy (range 21-88 Gy). Results: All patients were evaluable for treatment response and outcome. We found no differences between treatment approaches in terms of response rate, progression-free survival (PFS) and overall survival (OS). The local control rate was 94.3% and there was no statistically significant difference between the two groups. Progression to MM was recorded in 20/35 (57.1%) patients with SBP and in 1/18 (5.5%) patients with EMP. The median time to progression was 2.5 years (range 0.6-11). The 5-year PFS rate for all patients was 66.3% (95% CI: 53.9-81.4). Patients with SBP showed a worse PFS rate than EMP patients (53.0% vs 88.5%), with a statistically significant difference (P=0.0003). The total 5-year OS rate was 78.4% (95% CI: 67.3-91.3). Patients with SBP had a significantly worse OS rate than patient with EMP (71.9% vs 88.2%, respectively) (P=0.0290). Univariate analysis revealed that SBP and a larger tumor size (≥5 cm) were adverse prognostic factors affecting PFS (P=0.0027 and P=0.0498, respectively). SBP had an adverse effect also on OS (P=0.0405). In multivariate analysis, bone localization was the only independent worse prognostic factor for both PFS (P=0.0041) and OS (P=0.0216). Conclusions: Patients with SBP have a significantly worse prognosis than patients with EMP, underlining that they are indeed two different entities within the spectrum of plasma cells dyscrasias. The use of modern testing is mandatory to better characterize the patients’ risks of progression and to exclude an occult MM, especially in SBP. There is also a need for further prospective studies with large series of patients evaluating SBP and EMP separately, to elucidate the role of prognostic factors and treatment options for these conditions. Table 1 Characteristics Patient (number) Sex, mean (%) Male Female 33 (62.3)20 (37.7) Age (years) Median (range) ≤ 60 years, mean (%) 56.81 (27-80)33 (62.3) Histological type SBP mean, % EMP mean, % 35 (66)18 (34) Tumor size atDiagnosis, number (%) ≤5 cm 〉 5 cm N/A 19 (35.8)20 (37.7)14 (26.5) Serum M protein (%) Positive Negative 27 (50.9)26 (49.1) Urinary B-J protein Positive Negative 6 (11.3)47 (88.7) SBP Anatomic site Vertebral column Long tubal bone Sternum Ribs Craniofacial bone Scapula 17 (48)5 (14)4 (11)3 (8.5)3 (8.5)3 (8.5) EMP Anatomic site Upper respiratory tract Paranasal sinus Lymph nodes GI tract testis 9 (50)4 (22)2 (11)2 (11)1 (6) Disclosures Petrucci: Jansse-Cilag: Honoraria; Celgene: Honoraria; Sanofi: Honoraria; Bristol-Myers Squibb: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V124.21.3455.3455

Language: English

Publisher: American Society of Hematology

Publication Date: 2014

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Cardiovascular & Hematological Agents in Medicinal Chemistry, Bentham Science Publishers Ltd., Vol. 14, No. 1 ( 2016-06-13), p. 68-74

Type of Medium: Online Resource

ISSN: 1871-5257

URL: Article

DOI: 10.2174/1871525714666160405110833

Language: English

Publisher: Bentham Science Publishers Ltd.

Publication Date: 2016

SSG: 15,3