Patients with Acute Myelogenous Leukemia (AML) or High-Risk Myelodysplastic Syndrome (HR-MDS) Treated with Targeted Therapy May Benefit from Prophylactic Measures Against Infections.

Abstract Targeted therapy (TT) has emerged as an alternative for patients (pts) 60 years or older with hematologic malignancies. It has been suggested that these approaches produce fewer and less severe side effects than conventional chemotherapy (CC) and could potentially decrease mortality. In the current study, pts with AML or HR-MDS treated with TT and CC were compared with regard to infectious complications and induction mortality. Supportive care measures for pts on CC were given according to our departmental guidelines (protective environment (PE) was offered and antibacterial, antifungal and antiviral prophylaxis were given from D1 to ANC ≥ 500). Pts on TT were given supportive care measures according to protocol requirements. HR-MDS pts: 29 pts were treated with TT and 13 with CC. Pts on TT were significantly older than those on CC (median age: 66(r: 46–85) and 59(r: 17–73) respectively, p=0.02). All 42 pts (TT and CC) had Zubrod performance status (PS) ≤ 2. 16/29 (90%) pts on TT received Decitabine; 2 pts received 5-AZA containing regimens and 1 pt received rosiglitazone + targetrin. Nine pts (69%) on CC had high-dose ara-C (HDAC) containing regimens; 1 pt received cloretazine + hydrea and 3 pts had low-dose ara-C (LDAC) + clofarabine. AML pts: 43 pts were treated with TT and 282 received CC. Pts on TT were significantly older than those on CC (median age: 75(r: 39–86) and 62(r: 17–84) respectively, p<0.001). The majority of the pts in TT (91%) and CC (97%) had PS ≤ 2. Decitabine was given to 40% (17/43) of pts on TT, 25% received 5-AZA containing regimens, 35% had others. HDAC containing regimens were given to 60% of pts on CC and clofarabine and/or LDAC to 40%. Table 1 and 2 show outcome and infectious episodes (IE) in pts with MDS and AML, respectively. Conclusions: Although pts with AML or HR-MDS treated with TT develop significantly fewer number of IE compared to pts treated with CC the severity of such infections lead to similar mortality rate than pts treated with CC. Pts treated with TT may benefit from prophylactic measures against infections. Table 1 Outcome in MDS TT (N=29) CC (N=13) 12 aspergillosis, 1 MRSA sepsis; 2p=ns Response, n(%) Overall response 18(62) 8(61) Resistant 8(28) 4(31) Induction death 3(10) 1(8) p=0.787 Cause of Death, n(%) Infections 3(100)1 - Progressive disease - 1(100) Pts on prophylaxis, n(%) Fungal 11(38) 12(92) p=0.001 Bacterial 19(66) 9(69) p=0.810 Pts in PE, n(%) 0 10(77) p<0.001 Pts with IE, n(%) 15(52) 11(85) p=0.042 IE2, n(%) 19 14 Bacterial 5(26) 2(14) FUO 8(42) 9(64) Pneumonia unknown origin 2(11) 3(21) Fungal 2(11) 0 Others 2(11) 0 Table 2 Outcome in AML TT (N=43) CC(N=282) 1TT:sepsis=5, CC:fungal=4, sepsis=16; 2multiorgan failure; 3p=ns Response, n(%) Overall response 12(28) 180(64) Resistant 27(58) 67(24) Induction death 6(14) 35(12) p=0.779 Cause of death, n(%) Infection1 5(83) 20(57) MOF2 1(14) 7(20) Others - 8(23) Pts on prophylaxis, n(%) Fungal 16(37) 260(92) p=0.001 Bacterial 24(56) 282(100) p=0.001 Pts in PE, n(%) 6(14) 214(76) p<0.001 Pts with IE, n(%) 22(51) 247(88) p<0.001 IE3, n(%) 31 405 Bacterial 7(22) 88(22) FUO 13(42) 202(50) Pneumonia unknown origin 6(19) 93(23) Fungal 1(3) 10(2) Virus 2(6) 6(1) Others 2(6) 6(1)

Download Full-text

Infusion of “off-the-shelf” Third Party Ex Vivo Expanded Cord Blood Progenitor Cells As Supportive Care Following Clofarabine with High Dose Cytarabine and Granulocyte Colony-Stimulating Factor Priming for the Treatment of AML,

Blood ◽

10.1182/blood.v118.21.3640.3640 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3640-3640 ◽

Cited By ~ 2

Author(s):

Colleen Delaney ◽

Pamela S Becker ◽

Filippo Milano ◽

Ian Nicoud ◽

Shelly Heimfeld ◽

...

Keyword(s):

Supportive Care ◽

Phase I ◽

Progenitor Cells ◽

Fungal Infections ◽

Ex Vivo ◽

Infectious Complications ◽

High Dose ◽

Neutrophil Recovery ◽

Cell Product ◽

Hematopoietic Recovery

Abstract Abstract 3640 Regardless of patient age, prolonged neutropenia and infectious complications are common side effects of AML induction and salvage chemotherapy, requiring intensive supportive care and contributing to treatment failure. Thus, novel therapies that can abrogate prolonged pancytopenia and facilitate more rapid hematopoietic recovery are needed. Previously, we have demonstrated that the absolute number of repopulating cord blood (CB) hematopoietic stem/progenitor cells (HSPC) can be increased by culture with Notch ligand; recent data from a Phase I double CB transplant trial utilizing ex vivo expanded CB HSPC has suggested more rapid neutrophil recovery (Delaney et al, Nat med). We hypothesize that this expanded cell product, which is devoid of T cells, could be cryopreserved and then infused as an off-the-shelf non-HLA matched product to provide rapid but temporary donor myeloid engraftment and might also facilitate autologous hematopoietic recovery following AML therapy, thus reducing the infectious complications associated with therapy. In a cohort of 50 patients, Becker et al at the Fred Hutchinson Cancer Research Center have reported on the use of clofarabine and high dose ara-c, in combination with G-CSF (GCLAC) in a phase I/II trial for the treatment of relapsed/refractory AML (Becker et al, Br. J. Haematol, in press). GCLAC is profoundly immunosuppressive and myelosuppressive, with periods of prolonged neutropenia post-GCLAC ranging from 17 to 35 days (median time to ANC >500 is 21 days) in this cohort. Infection was the most frequent adverse event, with ≥ grade 3 bacterial and fungal infections seen in 40% of patients (including 1st and ≥ 2nd salvage patients). We now herein report the preliminary results of a phase I safety trial investigating the use of GCLAC plus infusion of off-the-shelf expanded and cryopreserved CB HSPC for patients with AML. To date, 12 adult patients with relapsed (n=8), primary refractory (n=2) or de novo high risk (n=2) AML have been enrolled and received GCLAC as their first salvage or initial induction therapy. The median age and weight was 55 years (range, 38 to 59 years) and 79.5 kg (range, 63.8 to 126) respectively. Patients received cycle 1 of GCLAC followed by infusion of off-the-shelf expanded CB HSPC 24 hours after completion of chemotherapy. Patients who achieved a complete morphologic remission and did not experience any toxicities associated with the expanded cell product were eligible to receive a 2nd cycle of GCLAC with cells if not proceeding directly to stem cell transplant. A total of 15 products have been infused in 12 patients. Five of the 12 patients were refractory to GCLAC and therefore non-evaluable for neutrophil recovery. The median time to achieve an ANC > 500 in the evaluable patients was 19 days (range 18 to 27) after cycle 1, as compared to 21 days (range 17 to 35) in the historical cohort of patients receiving GCLAC only without expanded cells. Importantly, in this phase I study, there have been no infusional toxicities from the expanded cells or adverse events attributed to the expanded cell product. Alloimmunization has not been observed as monitored by pre- and post-infusion panel reactive antibody assays to determine the presence of donor directed antibodies. Four of the 12 enrolled patients have experienced clinically significant infections (e.g., bacteremia, fungal infections) compared to 40% in the comparison cohort, and no infectious deaths have been observed. Finally, in contrast to the first cycle of chemotherapy where donor cells were detected in only one patient, 4 out of 4 patients who received a 2nd cycle of GCLAC with expanded cells were found to have transient donor contribution to myeloid recovery (by peripheral blood cell sorted DNA chimerism assay) one week after infusion of the cells ranging from 85 to 100% donor in the CD33/CD14 cell lineages. Expanded cells were also able to home to the marrow as evidenced by transient donor engraftment (range, 3 to 15%) in recipient marrows one week after expanded cell infusion. It is unclear whether this is related to increased marrow “space” or increased host immunosuppression following cycle 2. With this encouraging data, we are continuing accrual of newly-diagnosed patients. This approach may decrease complications of pancytopenia and allow delivery of more dose-intense therapy, particularly in patients with intermediate/favorable cytogenetics who are already relatively sensitive to GCLAC. Disclosures: Delaney: Sanofi-Oncology (formerly Genzyme): Clofarabine for the study supplied by Sanofi-Oncology (formerly Genzyme). Becker:Sanofi-Oncology (formerly Genzyme): Research Funding.

Download Full-text

Acute Myeloid Leukemia (AML). Diagnosis, Therapy and Outcome Results from Tawam Hospital. a Retrospective Review

Blood ◽

10.1182/blood.v124.21.5254.5254 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5254-5254

Author(s):

Arif Alam ◽

Ali Tahir ◽

Masood H Syed ◽

Sabir Hussain ◽

Amar Lal ◽

...

Keyword(s):

Older Adults ◽

Acute Myeloid Leukemia ◽

Supportive Care ◽

Induction Therapy ◽

Myeloid Leukemia ◽

Performance Status ◽

High Dose ◽

Lost To Follow Up ◽

Acute Myeloid

Abstract Introduction Acute Myeloid leukemia (AML) is a heterogeneous group of malignant disorders of myeloid hematopoetic cells. These cells have a maturation arrest in different stages of development leading to accumulation of immature cells. This gives rise to the different symptoms and signs of disease secondary to anemia, thrombocytopenia and neutropenia. The current WHO classification broadly divides AML into 4 main groups based on morphology, immunophenotyping, genetics and clinical features. These include AML with recurrent genetic abnormalities, AML with myelodysplasia related changes; therapy related AML and AML not otherwise specified (NOS). Therapeutically AML can be divided into 2 main groups; Acute promyelocytic leukemia (APML) and non APML. Methods Tawam Tumor registry was searched for patients with diagnosis of AML from January 2010 till December 2012. Patient records were then reviewed and data was collected. Results We identified 49 patients with pathologically confirmed diagnosis of AML. 19/49 patients were diagnosed with AML with recurrent cytogenetic, 5/49 with MDS related or therapy related and 25 with AML NOS Cytogenetic Analysis of this cohort of 49 patients with AML showed that 15 patients (30%) had APML with 15;17 translocation, 4 patients had 8;21 translocation, 5 had complex or poor risk cytogenetic while 13 had normal karyotype. In 12/49 patients Karyotyping failed due to growth failure. Status of FLT3 and NPM1 are not known for the entire cohort. Demographics The median age of the cohort was 38 years (range 20 to 84 years). Older adults (age 65 years or more) make a minority of this cohort (8%). Male to female ration was 3.5:1. Treatment In patients with Non APML Induction therapy was a combination of Cytarabine and Idarubicin for adults < 65 years of age and with good performance status. Older adults or adults with poor performance status or co-morbidities were either given hypomehtylating agents, Clofarabine or supportive care. Patients achieving complete remission (CR) were given consolidation with High Dose Cytarabine (HIDAC) as per CALGB protocol. Only a minority of patients were able to go for allogeneic stem cell transplantation in CR1 Patients with APML were treated with ATRA, Idarubicin/Mitoxantrone and Cytarabine as per PETHEMA protocol on a risk adjusted plan. This was followed by 2 year maintenance with ATRA, 6 MP and Methotrexate. Outcome of Treatment In non APML patients 62 % (17) achieved CR with induction therapy. Induction therapy failure was observed in 18 % (5) while there were 5 early deaths observed (during aplasia). 7 patients were treated with hypomethylating agents or best supportive care. Only 1patient was able to achieve CR (after cycle 4 of 5-azacitidine). Consolidation therapy was given to 17 patients achieving CR. With a median follow up of 15 months (range 9-24 months) 9 patients are alive and disease free while 17 patients have been lost to follow up. 8 out of these 17 patients were in remission at their last follow up. In APML patients the CR rate was 93%. There were no cases of induction failure and only 1 case of early death (7%) due to hemorrhage. With a median follow up of 17 months (range 11-41 months) 11 patients are in molecular CR while 3 have been lost to follow up. Conclusion This is the first analysis of patients who were diagnosed with AML in a tertiary care center in UAE. The results show that the median age of patients our cohort is low as compared to international reports (approximately 38 vs. 65 years). Older adults (> 65 years of age) make only a minority of the AML cohort in Tawam Hospital. Response to induction therapy is comparable to international standards (60-80%) for AML and > 90% for APML. We also report a twofold higher incidence of APML as compared to internationally reported data (30% vs.12%). This has a very significant diagnostic and therapeutic impact on the management of AML patients at our institute leading to increase vigilance and institution of ATRA at the earliest clinical suspicion of APML. Disclosures Alam: BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Hussain:BMS: Honoraria; Novartis: Honoraria. Lal:BMS: Honoraria; novartis: Honoraria.

Download Full-text

Sequential High Dose Immuno-Chemotherapy Followed by Autologous Peripheral Blood Stem Cell Transplantation for Patients with Untreated Primary Central Nervous System Lymphoma - a Multicentre Study by the Collaborative PCNSL Study Group Freiburg

Blood ◽

10.1182/blood.v120.21.302.302 ◽

2012 ◽

Vol 120 (21) ◽

pp. 302-302 ◽

Cited By ~ 15

Author(s):

Gerald Illerhaus ◽

Kristina Fritsch ◽

Gerlinde Egerer ◽

Monika Lamprecht ◽

Nikolas von Bubnoff ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Stem Cell ◽

Complete Remission ◽

Performance Status ◽

Central Nervous System Lymphoma ◽

Infectious Complications ◽

Induction Treatment ◽

High Dose ◽

Grade 3

Abstract Abstract 302 Background: Primary central nervous system lymphoma (PCNSL) is an aggressive non-Hodgkin′s lymphoma with poor prognosis. Addition of methotrexate (MTX) to whole brain radiotherapy (WBRT) has improved the prognosis of patients (pts) with PCNSL, but a significant proportion are still not cured. Preliminary reports suggested that dose-intensified chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) are highly effective in the treatment of newly-diagnosed PCNSL in younger pts. To strengthen the evidence of this approach, we initiated a prospective multicenter phase II study with early HDT and ASCT to investigate efficacy, safety and survival. This trial is registered at ClinicalTrials.gov (NCT 00647049). Methods: Immunocompetent pts <65 years with untreated biopsy proven PCNSL were eligible. Induction treatment consisted of 4 repetitive cycles of MTX (8g/m2) and 2 cycles cytarabine (2×3g/m2) and thiotepa (TT, 40mg/m2). Rituximab (375mg/m2) was added by amendmend after 2 included patients; it was given on day −7 before induction treatment and before each chemotherapy cycle. After the 2nd cycle cytarabine/TT stem-cells were collected after mobilisation with rG-CSF. The HDT regimen included carmustine (400mg/m2) and TT (4×5mg/kgBW) prior ASCT. Primary endpoint was complete remission (CR) 30 days after ASCT. Secondary end-points were overall-survival (OS), duration of response and toxicity. Patients not in complete remission after HDT and ASCT received WBRT. Results: From 2007 to 2011 79 pts (44 female, 35 male) were enrolled from 18 German centers and evaluable for analysis (median age 55 years, range 20–66). Seventy eight pts had aggressive B-cell lymphomas and one T-cell-lymphoma. Median Karnofsky performance status at diagnosis was 90% (range 30–100). After induction treatment, 73 of 76 (96%) evaluable pts responded, (26,9% CR, 55,7 PR). Seventy-three pts (96%) received HDT and ASCT according to protocol. Six pts were treated off-protocol due to low performance status (n=1), progressive disease (n=1) and infectious complications (n=4). Regarding the primary endpoint, CR was achieved in 77% and partial remission (PR) in 14% of patients (overall response rate 91%) after HDT and ASCT. Ten pts in PR after HDT and ASCT received consolidating WBRT. After a median follow-up of 28.8 months (range 1–63 mo) 1 and 2 years OS was 92% and 87%, respectively. Myelotoxicity was the most frequent CTC grade 3–4 toxicity with grade 3–4 infections in 41/73 pts (56,2%) during the transplant-phase. Two patients had lethal infectious complications during induction treatment with cytarabine/TT, three further pts died after HDT and ASCT due to severe infection (n=1), renal failure (n=1) and pneumonitis (n=1). Further results will be presented. Conclusion: Sequential MTX-based immuno-chemotherapy followed by carmustine/TT containing HDT and ASCT is highly effective and feasible in younger patients. Treatment related toxicity is of concern and comparable to non-high-dose protocols. Further randomised trials to compare HDT with conventional CT are needed. Disclosures: Illerhaus: Riemser: Honoraria.

Download Full-text

Az akut myeloid leukaemia gyógyszeres kezelése. Jelenlegi lehetőségek, jövőbeli kilátások

Orvosi Hetilap ◽

10.1556/650.2016.30433 ◽

2016 ◽

Vol 157 (22) ◽

pp. 843-848 ◽

Cited By ~ 1

Author(s):

Béla Telek ◽

László Rejtő ◽

Péter Batár ◽

Zsófia Miltényi ◽

Gyula Reményi ◽

...

Keyword(s):

Overall Survival ◽

Acute Myelogenous Leukemia ◽

Mutational Analysis ◽

Positive Impact ◽

Performance Status ◽

Myelogenous Leukemia ◽

Induction Treatment ◽

High Dose ◽

Additional Advantage ◽

Acute Myelogenous

Acute myelogenous leukemia is a heterogeneous disease. Recent molecular mutational analysis techniques have shed more light on different, genetically well characterised types of the disease. Treatment approach is uniform except for acute promyelocytic leukemia. Application of the “3 + 7” induction treatment has been the gold standard in the past 40 years. While the dose of cytarabine has not been changed, escalating daunorubicine dose in younger (<60 years) patients with good performance status to 90 mg/m2 had a positive impact on overall survival. High dose chemotherapy is tolerated poorly in patients older than 60 years of age and, as treatment is not curative in the elderly, improvement of overall survival and quality of life remains the main goal of management in these patients. Low intensity treatment is beneficial and can provide additional advantage over supportive care. Innovative and targeted therapy approaches might give promise to better management of patients with acute myelogenous leukemia. Orv. Hetil., 2016, 157(22), 843–848.

Download Full-text

Early lymphopenia after cytotoxic chemotherapy as a risk factor for febrile neutropenia.

Journal of Clinical Oncology ◽

10.1200/jco.1996.14.2.636 ◽

1996 ◽

Vol 14 (2) ◽

pp. 636-643 ◽

Cited By ~ 102

Author(s):

J Y Blay ◽

F Chauvin ◽

A Le Cesne ◽

B Anglaret ◽

D Bouhour ◽

...

Keyword(s):

Risk Factors ◽

Logistic Regression ◽

Risk Model ◽

Chemotherapy Regimen ◽

Performance Status ◽

Risk Groups ◽

High Dose ◽

Hematopoietic Growth Factors ◽

Prophylactic Measures ◽

Independent Risk Factors

PURPOSE Febrile grade four (ie, < or = 500/microL) neutropenia (FN) is a frequent life-threatening complication of cancer chemotherapy. Although its incidence correlates to the dose of chemotherapy, FN may occur after almost any cytotoxic regimen. At present, there is no predictive method to identify patients who will experience FN. PATIENTS AND METHODS Univariate and multivariate analyses of risk factors for FN were performed on a retrospective cohort of 112 consecutive patients treated with various chemotherapy regimens. Two independent risk factors were identified by the logistic regression and used to create a risk model for FN. The validity of the model was tested in three distinct groups of patients: two prospective groups of patients treated in two institutions (Centre Léon Berard [CLB] and Institut G. Roussy [IGR]) and the group of patients with intermediate- or high-grade non-Hodgkin's lymphoma (NHL) treated with the doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) regimen between 1988 and 1992 at CLB. RESULTS Within the retrospective group, 23 of 47 (49%) patients with lymphocyte counts < or = 700/microL at day 5 after chemotherapy experienced FN compared with seven of 65 (11%) of other patients (P = .00002). The type of chemotherapy (high dose v others) was also significantly correlated to FN (48% v 11%, P = .0003). Age, performance status, the number of previous chemotherapy cycles, or polymorphonuclear leukocyte (PMN) counts, were not significantly correlated to the incidence of FN in univariate analyses. Two independent risk factors were identified in the logistic regression: day 5 lymphocyte counts (beta = 1.97 +/- 0.53) and the type of chemotherapy regimen (beta = 1.91 +/- 0.53). The calculated probability to experience FN in patients with none, one, and both of these risk factors was 4.3%, 24.0%, and 68.8%, respectively. The validity of this model was tested in the three groups of patients used as validation samples. The observed incidences of FN in the above defined risk subgroups were 3%, 19%, and 67%, respectively, within the CLB prospective series and 6%, 19%, and 75% within the IGR prospective series. In the ACVBP group, the incidence of FN was 33% and 72%, respectively, in patients from the intermediate- and high-risk groups. In the two prospective groups and in the ACVBP series, the observed numbers of FN in the different risk groups did not differ significantly from those calculated by the model (P = .89, P = .86, and P = .72 for these three groups, respectively). CONCLUSION Day 5 lymphocyte counts < or = 700/microL and the type of chemotherapy regimen enable oncologists to define subgroups of patients treated with chemotherapy as those with a high intermediate, and low risk of FN. These criteria could be used to select subjects in whom prophylactic measures for FN, in particular hematopoietic growth factors, should be proposed.

Download Full-text

312 Female sex independently predicts adjuvant immunotherapeutic benefit from CTLA4 immune checkpoint inhibition

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0312 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A339-A339

Author(s):

Ahmad Tarhini ◽

Ni Kang ◽

Sandra Lee ◽

F Stephen Hodi ◽

Gary Cohen ◽

...

Keyword(s):

Overall Survival ◽

Treatment Efficacy ◽

Significant Interaction ◽

Cox Regression ◽

Performance Status ◽

Phase Iii ◽

High Dose ◽

List Type ◽

Female Sex ◽

Interaction Term

BackgroundSex differences in tumor immunity and response to immunotherapy were shown in murine models and descriptive analyses from recent clinical trials. Female sex hormones have been implicated in melanoma development and response to systemic therapy. We hypothesized a gender difference in response to adjuvant immunotherapy with ipilimumab (3 or 10 mg/kg; ipi3 or ipi10) versus high dose IFNα (HDI) as tested in the E1609 trial.MethodsE1609 demonstrated significant overall survival (OS) benefit with ipi3 versus HDI.1 We investigated treatment efficacy between ipi and HDI in the subgroups by sex (female, male), age (< 55 or ≥55), stage at study entry (IIIB, IIIC, M1a/1b), ECOG performance status (PS 0, 1), ulceration (yes, no), primary tumor (known, unknown), number of lymph nodes involved (0, 1, 2–3, 4+). Forest plots were created to compare OS and RFS with ipi3 vs. HDI and ipi10 vs. HDI using the concurrently randomized ITT populations. For the estimated HRs, 95% confidence intervals were created for all subgroups.ResultsThe subgroups of female, stage IIIC, PS=1, ulcerated, in-transit without lymph node involvement demonstrated significant improvement in overall survival (OS) and/or relapse free survival (RFS) with ipi3 versus HDI as summarized in table 1. Female sex was significant for both OS and RFS and was further explored. In investigating RFS with ipi3 versus HDI, a multivariate Cox regression model including sex, treatment and interaction term of sex*treatment, indicated a significant interaction between sex and treatment (P = 0.026). Including sex, PS (0 vs. 1), age (<55 vs. 55+), ulceration (yes vs. no), stage (IIIB, IIIC, M1a, M1b), treatment and interaction term of sex*treatment, indicated a significant interaction between sex and treatment (P = 0.024). While similar trends were seen, no significant interactions between sex and treatment effect were found in the OS multivariate analysis or in the comparison of ipi10 versus HDI. When exploring age, in the univariate analyses in the ipi3 versus HDI comparison older women appeared to drive most of the difference (age ≥55: OS, P=0.02 and RFS, P=0.08; differences non-significant for women <55). Table 1.Abstract 312 Table 1Treatment efficacy between ipi3 and HDI by subgroupConclusionsFemale sex was independently associated with RFS adjuvant immunotherapeutic benefit from ipi3, supporting a potentially important role for female related factors in the immune response against melanoma, and these warrant further investigation.Trial RegistrationNCT01274338Ethics ApprovalThe study protocol was approved by the institutional review board (IRB) of each participating institution and conducted in accordance with Good Clinical Practice guidelines as defined by the International Conference on Harmonisation. This study was monitored by the ECOG-ACRIN DataSafety Monitoring Committee and the NCI.ConsentAll patients provided IRB-approved written informed consent.ReferenceTarhini AA, Lee SJ, Hodi FS, Rao UNM, Cohen GI, Hamid O, Hutchins LF, Sosman JA, Kluger HM, Eroglu Z, Koon HB, Lawrence DP, Kendra KL, Minor DR, Lee CB, Albertini MR, Flaherty LE, Petrella TM, Streicher H, Sondak VK, Kirkwood JM. Phase III Study of Adjuvant Ipilimumab (3 or 10 mg/kg) Versus High-Dose Interferon Alfa-2b for Resected High-Risk Melanoma: North American Intergroup E1609. J Clin Oncol. 2020 Feb 20;38(6):567–575. PMID: 31880964.

Download Full-text

Idiopathic granulomatous mastitis: challenges of treatment in iranian women

BMC Surgery ◽

10.1186/s12893-021-01210-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Leyla Shojaee ◽

Nasrin Rahmani ◽

Siavash Moradi ◽

Asieh Motamedi ◽

Gholamali Godazandeh

Keyword(s):

Recurrence Rate ◽

Low Dose ◽

Unknown Origin ◽

Surgical Excision ◽

Chronic Inflammatory Disease ◽

High Dose ◽

Granulomatous Mastitis ◽

Idiopathic Granulomatous Mastitis ◽

Results Of Treatment ◽

Information Treatment

Abstract Background and objective As a chronic inflammatory disease of an unknown origin, the treatment of granulomatous mastitis has always been controversial. According to some researchers, surgical treatment and certain medications, especially steroids, are more effective in treating the disease. This study aimed at evaluating the results of treatment in a group of patients with granulomatous mastitis. Materials and methods This longitudinal cohort study evaluated the treatment outcomes of 87 patients with pathology-confirmed granulomatous mastitis referred to the surgical clinic of Central Hospital in Sari, Iran. Demographic, clinical, and pathological information, treatment methods and results, and the recurrence rate were analyzed. Findings A total of 87 female patients with granulomatous mastitis aged 22–52 years with a mean age of 34 years were evaluated. All patients had palpable masses; the breast masses were painful in 48.3% of patients, and 55.2% of patients suffered from erythema and inflammation, and8% had fistulas and ulcers at the inflammation site. The patients were followed-up for an average duration of 26 months (8–48 months) after treatment and recovery. The overall recurrence rate was 24.1%, and the recurrence rate was 29.4% in patients underwent surgery, 34.8% in patients received high-dose prednisolone, and 17% in those received low-dose prednisolone together with drainage (p < 0.001). Conclusions According to the results, the low-dose prednisolone plus drainage was more effective with a lower recurrence rate than only surgical excision or high-dose prednisolone. In fact, the use of minimally invasive methods such as drainage plus low-dose steroids is a more effective method with fewer side effects than the other two methods.

Download Full-text

Monotherapy with Intravenous Followed by Oral High-Dose Ciprofloxacin versus Combination Therapy with Ceftazidime plus Amikacin as Initial Empiric Therapy for Granulocytopenic Patients with Fever

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.44.12.3264-3271.2000 ◽

2000 ◽

Vol 44 (12) ◽

pp. 3264-3271 ◽

Cited By ~ 43

Author(s):

Helen Giamarellou ◽

Harry P. Bassaris ◽

George Petrikkos ◽

Wilhelm Busch ◽

Michel Voulgarelis ◽

...

Keyword(s):

Randomized Study ◽

Empirical Therapy ◽

Unknown Origin ◽

Empiric Therapy ◽

Oral Route ◽

Severe Neutropenia ◽

Combination Group ◽

High Dose ◽

Standard Regimen ◽

Oral Ciprofloxacin

ABSTRACT The aim of the present study was to obtain clinical experience with the use of high-dose ciprofloxacin as monotherapy for the treatment of febrile neutropenia episodes (granulocyte count, <500/mm3) compared to a standard regimen and to clarify whether ciprofloxacin administration may be switched to the oral route. In a prospective randomized study ciprofloxacin was given at 400 mg three times a day (t.i.d.) for at least 72 h followed by oral administration at 750 mg twice a day (b.i.d). That regimen was compared with ceftazidime given intravenously at 2 g t.i.d. plus amikacin given intravenously at 500 mg b.i.d. The frequency of successful clinical response without modification at the end of therapy was almost identical for ciprofloxacin (50% [62 of 124 patients]) compared with that for ceftazidime plus amikacin (50.8% [62 of 122 patients]) in an intent-to-treat analysis; the frequencies were 48.3% (57 of 118 patients) versus 49.6% (56 of 113 patients), respectively, in a per-protocol analysis (P values for one-sided equivalence, 0.0485 and 0.0516, respectively; δ = 10%), with no significant differences among patients with bacteremia and other microbiologically or clinically documented infections and fever of unknown origin. For 82 (66.1%) patients, it was possible to switch from parenteral ciprofloxacin to the oral ciprofloxacin, and the response was successful for 61 (74.4%) patients. The efficacies of the regimens against streptococcal bacteremias were 16.6% (one of six patients) for the ciprofloxacin group and 33.3% (one of three patients) for the combination group (it was not statistically significant), with one breakthrough streptococcal bacteremia observed among the ciprofloxacin-treated patients. Adverse events were mostly self-limited and were observed in 27 (20.6%) ciprofloxacin-treated patients and 26 (19.7%) patients who were receiving the combination. This study demonstrates that high-dose ciprofloxacin given intravenously for at least 3 days and then by the oral route is therapeutically equivalent to the routine regimen of intraveneous ceftazidime plus amikacin even in febrile patients with severe neutropenia (polymorphonuclear leukocyte count, <100 mm3). However, it is very important that before an empirical therapy is chosen each hospital determine bacteriologic predominance and perform resistance surveillance.

Download Full-text

Randomized Controlled Trial of Azacitidine in Patients With the Myelodysplastic Syndrome: A Study of the Cancer and Leukemia Group B

Journal of Clinical Oncology ◽

10.1200/jco.2002.04.117 ◽

2002 ◽

Vol 20 (10) ◽

pp. 2429-2440 ◽

Cited By ~ 1200

Author(s):

Lewis R. Silverman ◽

Erin P. Demakos ◽

Bercedis L. Peterson ◽

Alice B. Kornblith ◽

Jimmie C. Holland ◽

...

Keyword(s):

Quality Of Life ◽

Randomized Controlled Trial ◽

High Risk ◽

Myelodysplastic Syndrome ◽

Supportive Care ◽

Controlled Trial ◽

Myelogenous Leukemia ◽

Leukemic Transformation ◽

Randomized Controlled

PURPOSE: Patients with high-risk myelodysplastic syndrome (MDS) have high mortality from bone marrow failure or transformation to acute leukemia. Supportive care is standard therapy. We previously reported that azacitidine (Aza C) was active in patients with high-risk MDS.PATIENTS AND METHODS: A randomized controlled trial was undertaken in 191 patients with MDS to compare Aza C (75 mg/m2/d subcutaneously for 7 days every 28 days) with supportive care. MDS was defined by French-American-British criteria. New rigorous response criteria were applied. Both arms received transfusions and antibiotics as required. Patients in the supportive care arm whose disease worsened were permitted to cross over to Aza C.RESULTS: Responses occurred in 60% of patients on the Aza C arm (7% complete response, 16% partial response, 37% improved) compared with 5% (improved) receiving supportive care (P < .001). Median time to leukemic transformation or death was 21 months for Aza C versus 13 months for supportive care (P = .007). Transformation to acute myelogenous leukemia occurred as the first event in 15% of patients on the Aza C arm and in 38% receiving supportive care (P = .001). Eliminating the confounding effect of early cross-over to Aza C, a landmark analysis after 6 months showed median survival of an additional 18 months for Aza C and 11 months for supportive care (P = .03). Quality-of-life assessment found significant major advantages in physical function, symptoms, and psychological state for patients initially randomized to Aza C.CONCLUSION: Aza C treatment results in significantly higher response rates, improved quality of life, reduced risk of leukemic transformation, and improved survival compared with supportive care. Aza C provides a new treatment option that is superior to supportive care for patients with the MDS subtypes and specific entry criteria treated in this study.

Download Full-text