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2.
Ann Hematol ; 97(9): 1671-1682, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29756171

ABSTRACT

We evaluated progression-free survival (PFS) rate of patients treated with lenalidomide/dexamethasone (Len/Dex), the efficacy of the combination, and the prognostic significance of treatment at biochemical vs. clinical relapse on PFS in 207 consecutive myeloma patients treated with Len/Dex in second line, according to routine clinical practice in Greece. First-line treatment included bortezomib-based (63.3%) or immunomodulatory drug-based (34.8%) therapies; 25% of patients underwent autologous stem cell transplantation. Overall response rate was 73.4% (17.8% complete response and 23.7% very good partial response); median time to best response was 6.7 months. Overall, median PFS and 12-month PFS rate was 19.2 months and 67.6%, respectively. 67.5% of patients had biochemical relapse and 32.5% had clinical relapse prior to initiation of Len/Dex. Median PFS was 24 months for patients treated at biochemical relapse vs. 13.2 months for those treated at clinical relapse (HR:0.63, p = 0.006) and the difference remained significant after adjustment for other prognostic factors. Type of relapse was the strongest prognostic factor for PFS in multivariate analysis. These real-world data confirm the efficacy of Len/Dex combination at first relapse; more importantly, it is demonstrated for the first time outside a clinical trial setting that starting therapy with Len/Dex at biochemical, rather than at clinical relapse, is a significant prognostic factor for PFS, inducing a 37% reduction of the probability of disease progression or death.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Dexamethasone/administration & dosage , Multiple Myeloma/drug therapy , Multiple Myeloma/pathology , Thalidomide/analogs & derivatives , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , Chemotherapy, Adjuvant , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Lenalidomide , Male , Middle Aged , Multiple Myeloma/diagnosis , Multiple Myeloma/epidemiology , Practice Patterns, Physicians'/statistics & numerical data , Prognosis , Recurrence , Retrospective Studies , Survival Analysis , Thalidomide/administration & dosage
3.
Ann Hematol ; 94(12): 2033-42, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26420061

ABSTRACT

Involvement of the central nervous system (CNS) is a rare complication of multiple myeloma (MM). Herein, we have described the incidence, characteristics, prognostic factors for post CNS-MM survival, and outcome of CNS-MM and explored the efficacy of novel agents (NA) (thalidomide, bortezomib, lenalidomide) in this setting. Between 2000 and 2013, 31 (0.9 %) out of 3408 newly diagnosed symptomatic MM patients, consecutively diagnosed and treated during the same period in 12 Greek centers, developed CNS-MM (M/F 15/16, median age 59 years, range 20-96 years; newly diagnosed/relapsed-refractory 2/29; median time to CNS-MM diagnosis 29 months). Clinical and laboratory characteristics were retrospectively recorded. Twenty-six percent of patients had circulating plasma cells (PCs) or plasma cell leukemia (PCL) at CNS-MM and 39 % had skull-derived plasmacytomas, suggesting hematological and contiguous spread. Treatment for CNS-MM was offered in 29/31 patients and 11/29 responded (NA 18/29, additional radiotherapy 9/28, intrathecal chemotherapy 13/29). The median post CNS-MM survival was 3 months (95 % CI 1.9-4.1) and did not differ between patients treated with NA and/or radiotherapy vs. others. In the multivariate analysis, prior treatment of MM with NA, extramedullary disease (EMD) during MM course (i.e., plasmacytomas, circulating PCs, or documented PCL) and abnormally high LDH at MM diagnosis were independent prognostic factors, whereas treatment of CNS-MM with NA did not predict for post CNS-MM survival. Despite the relatively limited number of patients due to the rarity of CNS-MM, our results suggest that NA do not seem to improve post CNS-MM survival. Patients with EMD display shortened post CNS-MM survival and should be followed thoroughly.


Subject(s)
Central Nervous System Neoplasms/mortality , Central Nervous System Neoplasms/therapy , Multiple Myeloma/mortality , Multiple Myeloma/therapy , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Greece/epidemiology , Humans , Male , Middle Aged , Survival Rate
4.
Med Mycol ; 46(3): 259-63, 2008 May.
Article in English | MEDLINE | ID: mdl-17885950

ABSTRACT

In this report we describe a patient suffering from chronic myeloid leukemia (CML), who was treated for 4.5 years with imatinib and developed pneumonia caused by two Candida species, i.e., C. krusei and C. glabrata. The patient was in complete hematologic remission and molecular analyses did not display the presence of TLR2-R752Q, TLR4-D299G and TLR4-T399I polymorphisms that may predispose individuals to fungal infections. This case report indicates that in some patients, as previously observed, the long-term administration of targeted therapy might affect immunity and predispose patients to opportunistic and life-threatening fungal infections.


Subject(s)
Candida/isolation & purification , Candidiasis/microbiology , Leukemia, Myeloid/complications , Leukemia, Myeloid/drug therapy , Piperazines/adverse effects , Pneumonia/microbiology , Pyrimidines/adverse effects , Aged , Benzamides , Candidiasis/genetics , Humans , Imatinib Mesylate , Leukemia, Myeloid/genetics , Lung/diagnostic imaging , Male , Opportunistic Infections/genetics , Opportunistic Infections/microbiology , Piperazines/therapeutic use , Pneumonia/genetics , Polymorphism, Genetic , Pyrimidines/therapeutic use , Radiography , Toll-Like Receptor 2/genetics , Toll-Like Receptor 4/genetics
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