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  • 1
    In: Annals of Hematology, Springer Science and Business Media LLC, Vol. 91, No. 9 ( 2012-9), p. 1451-1458
    Type of Medium: Online Resource
    ISSN: 0939-5555 , 1432-0584
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2012
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  • 2
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 4825-4825
    Abstract: The FCR combination in a phase III study (Blood 102, abstract #373, p110a,2003) has shown promising results in the treatment of chronic lymphocytic leukemia (CLL) patients leading in increase of proportion of complete remissions and improved survival. Based on these encouraging results we tried to study the efficacy and safety of the FCR combination in patients of our Haematologic Unit. Seventeen patients, 8 males and 9 females with a median age of 69,5 years old, with relapsed/refractory or de novo CLPD ( 9 CLL and 8 NHL patients) were enrolled in this study between February 2002 and August 2004. Fifty percent of CLL patients had Rai stage I/II and the rest 50% had Rai stage III/IV disease. Four NHL patients had also Ann Arbor stage I/II and the rest four Ann Arbor stage III/IV disease. They were treated with Rituximab 375 mg/m2 on day1 in combination with Fludarabine and Cyclophosphamide ( 25 mg/m2 and 250 mg/m2 respectively) for days 2 to 4, every 4 weeks, for 6 consecutive cycles. Nine patients had a history of a prior unsuccessful treatment. Overall, 14 out of 17 evaluable patients were responsive to the treatment [12 patients complete response (CR) and 2 patients partial response (PR), overall response rate (ORR) 82%]. The remaining 3 patients did not show any response (NR), 2 progressive and 1 stable disease. Hematological toxicity was acceptable ( grade 2–3 neutropenia in 6/17 patients, grade 2–3 anemia and thrombocytopenia in 2/17 patients). There were no septic episodes except one case with neutropenic fever. There were no adverse events like nausea or vomiting except one patient with a serious anaphylactic reaction due to Rituximab administration. Three CLL patients died because of stable or progressive disease. In conclusion, this preliminary report suggests that the FCR regimen is an effective and safe treatment for CLPD patients, achieving higher CR rates than previous treatments. A longer follow up of a larger number of patients is required to confirm an improved survival in these patients.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
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  • 3
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 4740-4740
    Abstract: Background: The treatment of patients with chronic lymphocytic leukemia (CLL) with Rituximab in combination with fludarabine and cyclophosphamide was reported to be more efficacious, in terms of complete and molecular remission compared with historical data for fludarabine plus cyclophosphamide (S.O’Brien, Haematologica2002; 87:50–53). Aims: Evaluation of the clinical efficacy and toxicity of the FCR combination in patients of our Haematologic Centre. Methods: Seventeen patients, 8 males and 9 females with a median age of 69,5 years, with relapsed/refractory or de novo CLPD (9 CLL and 8 NHL patients) were enrolled in this study between February 2002 and August 2004. Fifty percent of CLL patients had Rai stage I/II and the rest 50% had Rai stage III/IV disease. Four NHL patients had an International Prognostic Index (IPI) 2, one patient IPI 3 and three patients IPI 4. All patients were treated with Rituximab 375 mg/m2 on day1 in combination with Fludarabine and Cyclophosphamide (25 mg/m2 and 250 mg/m2 respectively) for days 2 to 4, every 4 weeks, for 6 consecutive cycles. Nine patients had a history of a prior unsuccessful treatment. Results: Overall, 14 out of 17 evaluable patients (82%) were responsive to the treatment [12 patients (70%) complete response (CR) and 2 patients (12%) partial response (PR)]. The remaining 3 patients had progressive disease (NR). Hematological toxicity was acceptable (grade 2–3 neutropenia in 6/17 patients, grade 2–3 anemia and thrombocytopenia in 2/17 patients). There were no septic episodes except one case with neutropenic fever. There were no adverse events like nausea or vomiting except one patient with a serious anaphylactic reaction due to Rituximab administration. Three CLL patients died because of progressive disease. Summary/conclusions: this preliminary report suggests that the FCR regimen is an effective and safe treatment for CLPD patients, achieving higher CR rates than previous treatments. A longer follow up of a larger number of patients is required to confirm an improved survival in these patients.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
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  • 4
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 4907-4907
    Abstract: Background: The deletion of genomic sites harboring TSGs is known to be a powerful prognostic indicator in various chronic hematologic malignancies. However, the clinical significance of TSGs loss in MDS has not been thoroughly investigated. Aims: To summarize our experience on the incidence and essential clinical correlates of TSGs deletions in MDS, providing preliminary results from the study of 27 patients. Methods: The study included 17 men and 10 women (median age 74; range 38–84 years) with a documented diagnosis of MDS. The distribution of FAB subtypes was RA in 13, RARS in 3, RAEB in 6, RAEB-T in 4 and CMML in 1 case. According to the IPSS stratification, 5 patients were characterized as “low-risk”, 16 as “intermediate-risk” (11 as INT-1 and 5 as INT-2) and 6 as “high-risk” patients. The diagnostic bone marrow smears were studied with fluorescence in-situ hybridization (FISH) for deletions of chromosome regions 9p21 (p16/p14 and p15 genes), 9q34, 12p13 (TEL gene), 13q14 (RB1 gene D13S319 locus) and 17p13 (p53 gene). Results: A deletion in at least one of the chromosome regions or loci studied was detected in 10 patients (37%). In 6 of them, more than one region locus was lost, making up a total of 20 deletions. The commonest finding was loss of the 17p13 region (5 cases; two of them homozygous), followed by 9p21 loss (5 cases; one of them homozygous). Overall, the presence of TSGs deletions was associated with complex karyotype, high IPSS score and risk of death (regardless of leukemic progression). Interestingly, deletion in at least one of the TSGs studied was found in 5 of the 17 patients presenting with normal karyotype. In 3 of these patients, the MDS progressed to acute leukemia. Two of the 5 patients died at one and six months from diagnosis of the MDS, without leukemic conversion. Summary/Conclusions: Deletions of TSGs are not uncommon in MDS. Interestingly, we have found that certain TSGs, such as the p16/p14 and p15 genes at 9p21, the loss of which is mostly involved in the initiation or progression of lymploid neoplasms, are also frequently deleted in MDS. Overall, TSGs deletion in this small group of patients is apparently associated with other adverse biological and clinical features and poor outcome. Therefore, these preliminary observations justify the expansion of the study in a larger patient cohort, in order to clarify if the loss of certain TSGs is an independent prognostic factor in MDS and, thus, may be of help in the initial diagnostic approach and risk stratification of the patients.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
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  • 5
    In: Journal of Research and Practice on the Musculoskeletal System, Hylonome Publications, Vol. 02, No. 01 ( 2018-03-01), p. 31-38
    Type of Medium: Online Resource
    ISSN: 2585-2787
    Language: Unknown
    Publisher: Hylonome Publications
    Publication Date: 2018
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  • 6
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 4617-4617
    Abstract: APL represents a particular subtype of acute myeloid leukemia with characteristic clinical features, as well as specific immunophenotypic, cytogenetic and molecular findings owing to the chromosomal translocation t(15;17). Anthracycline-based chemotherapy and All-Trans Retinoid Acid (ATRA) became the cornerstone of APL treatment by improving significantly the long term outcome of patients, even though there is some controversy regarding the impact of this combination on the mortality of the induction phase. Herein, we analysed retrospectively the outcome of 16 consecutive adult APL patients who were diagnosed and treated in our Unit from 12/1998 to 10/2004. The analysis focuses more on the parameters of treatment-related mortality, cause of death and disease-free survival post AIDA chemotherapy. All patients were suffering from the classical form of APL and were homogeneously treated as follows: induction consisted of ATRA p.o. and idarubicin i.v. at conventional doses of 45mg/m2/d, from D1 to CR and 12mg/m2/d, D2,4,6,8 (total of 4 infusions), respectively. Dose modifications for elderly individuals were not allowed. Complete remitters were consolidated with 3 courses of chemotherapy without ATRA, where as non-remitters were taken off protocol and received other therapy. Patients in continuing hematological and molecular remission at the end of consolidation were administered maintenance therapy for 2 years with oral 6-MP at 90mg/m2/d, oral MTX weekly at 15mg/m2 and ATRA for 15 days every 3 months. In all cases, the morphological diagnosis of APL was confirmed by chromosome and immunophenotypic analysis of blasts in addition to molecular studies. The median age of our cohort was 55 years (range 31–78) and the male/female ratio was 12/4. Three patients (3/16, 19%) were ≥ 65 years at diagnosis. Two cases (2/16, 12%) presented with a leukocyte count of ≥10 x 103/mm3 while the median Wbc at presentation was 6.5 x 103/mm3. All cases had either clinical (haemorrhagic) or laboratory evidence of disseminated intravascular coagulation. Six patients (6/16, 37%) deceased during the induction phase from pulmonary bleeding (2 cases,days 8 and 13 respectively), intracerebral bleeding (1 case,day 6), myocardial infarction-cardiac arrest (1 case,day 5), respiratory distress syndrome secondary to ATRA syndrome (1 case, day 17), and sepsis-induced hemophagocytosis syndrome (1 case, day 38). All ten out of the 16 (63%) surviving patients achieved hematological and molecular CR and remain to date relapse-free in excellent clinical condition. The median overall survival and disease-free survival for the whole group is 25 months but the same parameters for the surviving patients is better at 42 months. Our results corroborate that in APL the AIDA protocol together with maintenance treatment is highly effective in producing sustained haematological and molecular remission. Despite this excellent antileukaemic activity, early mortality (37% in our cohort) caused chiefly by fatal bleeding and thrombotic events (four patients) limits considerably patient survival and deserves further research in order to improve long-term outcome.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
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  • 7
    In: Journal of Frailty, Sarcopenia and Falls, Hylonome Publications, Vol. 01, No. 04 ( 2016-12), p. 58-72
    Type of Medium: Online Resource
    ISSN: 2459-4148
    Language: Unknown
    Publisher: Hylonome Publications
    Publication Date: 2016
    detail.hit.zdb_id: 3024255-1
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  • 8
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 4372-4372
    Abstract: The value and exact type of intensive chemotherapy of unselected elderly AML patients in terms of overall survival (OS) and quality of life remains controversial. Despite recent improvements in supportive measures during cytotoxic therapy, elderly AML patients continue to exhibit lower remission rates, higher toxicity, more relapses and eventually a worse survival. The present analysis evaluates in a retrospective manner the outcome of 57 homogeneously treated AML patients 〉 60yrs during a period of 70 months (Nov 2001 to Aug 2007). The protocol schedule included an initial course of mitoxantrone+ cytarabine 3+5 (12mg/m2/d and 100mg/m2 q12h respectively) followed by a second abbreviated course of mitoxantrone+ cytarabine 2+5, followed by a final course of idarubicin+cytarabine+ thioguanine 2+7+7 (10mg/m2/d, 100mg/m2 q12h and 100mg/m2/d respectively). G-CSF at 5μg/Kg was added to all courses to accelerate hematopoietic recovery. Our patient population consisted of 30 cases of de novo AML and 27 cases of secondary AML (MDS 26, NHL 1) classified according to FAB as follows: M0 (6), M1 (7), M2 (25), M4 (7), M5 (4), M6 (6), hybrid-leukemia (2). Their median age was 70 yrs (range 63–80, mean 70,3 yrs) and M/F ratio was 35/22. Cytogenetic analysis was performed in 52/57 cases: 6/57 cases failed to produce metaphases, 32 cases revealed standard risk abnormalities (twenty six normal karyotype, six trisomy 8) and 7/52 cases had poor risk abnormalities. Leukocytosis 〉 50X109/L was noted in 12/57 and leukopenia 〈 5X109/L was noted in 22/57 patients. After a median observation period of 9 months (range 1–70) the following results are available: 26/57(45,6%) patients entered CR (15 de novo, 11 secondary) post-course 2 and their median OS is 15 months (range 2–63). An additional 6/57(10,5%) cases returned to a myelodysplastic phase without excess of blasts achieving thus partial hematological remission. The remaining 25/57(43,8%) patients proved primary resistant and deceased after a median of 3 months (range 1–22). One resistant case survive in remission attained off protocol. Within the group of remitters 3/26 deceaced from complications (MI, fungal infection, sepsis) before the next chemotherapy course. The remaining 16/26 remitters relapsed after a median of 8 months (range 1–12,5); fourteen of them deceaced and two are alive for 63 and 16 months respectively (one as a result of salvage treatment and the other with on going disease). Finally 7/26 cases remain alive and disease-free. Due to the short follow up, median OS for the whole cohort was estimated to date at 7,5 months. Conclusion: Combination chemotherapy with mitoxantrone and cytarabine is well-tolerated and reasonably effective in elderly AML patients. With a total response rate of 56,1% (CR+PR) and an induction death rate of 3,4%(2/57), the current schedule deserves further evaluation in a larger AML population. Furthermore, our data validate the improvement in survival of those patients achieving CR as suggested by other studies.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 9
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 4624-4624
    Abstract: The value and exact type of intensive chemotherapy of unselected elderly AML patients in terms of overall survival (OS) and quality of life remains controversial. The lack of large randomized trials comparing intensive to low dose treatment or to just supportive care as well as the selection bias observed in smaller studies in AML patients over 60 years contribute significantly to the clinical dilemma. Despite recent improvements in supportive measures during cytotoxic therapy, elderly AML patients continue to exhibit lower remission rates, higher toxicity, more relapses and eventually a worse survival. The present analysis evaluates in a retrospective manner the outcome of 39 homogeneously treated AML patients 〉 60yrs during a period of 44 months (Nov 2001 to Aug 2005). The protocol schedule included an initial course of mitoxantrone + cytarabine 3+5 (12mg/m2/d and 100mg/m2 q12h respectively) followed by a second abbreviated course of mitoxantrone + cytarabine 2+5, followed by a final course of idarubicin + cytarabine + thioguanine 2+7+7 (10mg/m2/d, 100mg/m2 q12h and 100mg/m2/d respectively). G-CSF at 5μg/Kg was added to all courses to accelerate hematopoietic recovery. Our patient population consisted of 22 cases of de novo AML and 17 cases of secondary AML (MDS 16, NHL 1) classified according to FAB as follows: M0 (5), M1 (4), M2 (19), M4 (3), M5 (2), M6 (5), hybrid-leukemia (1). Their median age was 70 yrs (range 63–80 yrs) and M/F ratio was 27/12. Cytogenetic analysis was performed in 33/39 cases: 6/33 cases failed to produce metaphases, 20/33 cases revealed standard risk abnormalities (seventeen normal karyotype, three trisomy 8) and 7/33 cases had poor risk abnormalities by MRC cytogenetic criteria. Leukocytosis 〉 50X109/L was noted in 6/39 and leukopenia 〈 5X109/L was noted in 19/39 patients. After a median observation period of 9 months (range 1–40) the following results are available: 19/39 (48,7%) patients entered CR (13 de novo, 7 secondary) post-course 2 and their median OS is 15,5 months (range 2–40). An additional 6/39 (15,3%) cases returned to a myelodysplastic phase without excess of blasts achieving thus partial hematological remission. The remaining 14/39 (35,8%) patients proved primary resistant and deceased after a median of 2,5 months (range 1–20) with one resistant patient surviving 20 months with on-going disease. Within the group of remitters 3/19 deceased from complications (MI, fungal infection, sepsis) before the next chemotherapy course. The remaining 11/19 remitters relapsed after a median of 7,5 months (range 1–30); nine of them deceased and two are alive as a result of salvage treatment. Finally 5/19 cases remain alive and disease-free (two interrupted after the second course). Conclusion: Combination chemotherapy with mitoxantrone and cytarabine is well-tolerated and reasonably effective in elderly AML patients fit enough to undergo chemotherapy regardless of karyotype and antecedent blood dyscrasia. With a total response rate of 64% (CR+PR) and an induction death rate of 5,1% (2/39), the current schedule deserves further evaluation in a larger AML population. Furthermore, our data validate the improvement in survival of those patients achieving CR as suggested by other studies.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 4588-4588
    Abstract: Hyper-CVAD represents an intensified program for the treatment of acute and chronic lymphoid malignancies. This protocol has been proposed as a highly efficient treatment for adult ALL with acceptable toxicity profile. Purpose: In our Institution, Hyper-CVAD was initiated in September 1999 and used as the primary treatment of adult ALL. We analyse and report here our results focusing on the efficacy and the toxicity of the program. Patients and methods: Patient population consisted of 24 de novo ALL (7 T-cell, 17 B-cell). M/F ratio was 11/13, median age 39 yrs,mean age 42,1 yrs (range 18–68 yrs). 7/24(29,1%) patients were older than 50yrs. Hyperleukocytosis of more than 100x109/L was present in 6/24(25%) cases (3 T-cell,3 B-cell), while splenomegaly, hepatomegaly and bulky disease were documented in 19/24, 17/24 and 1/24 cases respectively. Cytogenetic analysis was performed in 23/24 patients: in 11/23 it was normal, in 1/23 showed del(12), in 1/23 revealed just polyploidy and failed in 10/23 cases. Bcr-abl transcripts were detected in three cases. None of our patients presented with CNS disease (morphology & immunophenotyping). Median follow up was 12,5 months (range 1–65 mo). Treatment consisted of four cycles of Hyper-CVAD (including fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone) alternating with four cycles of methotrexate and cytarabine. All patients received intrathecal CNS prophylaxis and granulocyte stimulating factor support. Maintenance therapy consisted of two years of treatment with mercaptopurine, methotrexate, vincristine and prednisone (POMP). Imatinib was added in bcr-abl(+) cases. Results: Hematological complete remission was achieved in 21/24 (87,5%) de novo ALL cases: (11pts 〈 4wk, 10pts 〉 4wk ). Primary resistance was documented in 2/24 cases which subsequently received other therapeutic protocols and eventually deceased. One patient died in early induction. From the group of remmiters 11/21 are alive in CR after median DFS of 21mo (mean DFS 32mo, range 3–57). Another 7/21 remitters-including one post autologous transplantation- relapsed after median of 4,5 mo and six of them deceased. 6/21 patients underwent allogeneic transplantation (4 alive in CR, 2 deceased from complications). Regimen-related toxic deaths occurred in 4/23 cases whilst in remission status. 6/8 Τ-ALLs entered CR but half of them latter relapsed (two in consolidation and one in maintenance). CNS involvement during therapy on hyper-CVAD was not detected in the subgroup of resistant/progressive patients. Conclusions: Within the limitations of the small patient number and relatively short follow up we confirm the effectiveness of hyper-CVAD in de novo ALL, albeight at a lower than expected magnitude. Furthermore, we are unable to confirm the reported excellent outcome in T-ALL. Infectious complications were significant despite the administration of growth factors and prophylactic antibiotics. Hyper-CVAD can prevent leukemia extention to CNS in both responders and non responders.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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