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  • 1
    In: The Lancet Global Health, Elsevier BV, Vol. 12, No. 7 ( 2024-07), p. e1094-e1103
    Type of Medium: Online Resource
    ISSN: 2214-109X
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2024
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  • 2
    In: Metabolic Syndrome and Related Disorders, Mary Ann Liebert Inc, Vol. 19, No. 9 ( 2021-11-01), p. 483-490
    Type of Medium: Online Resource
    ISSN: 1540-4196 , 1557-8518
    Language: English
    Publisher: Mary Ann Liebert Inc
    Publication Date: 2021
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  • 3
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 5742-5742
    Abstract: Background: Treatment for post-transplant relapsed/refractory acute lymphoblastic leukemia (R/R-ALL) is not well defined. A majority of ALL relapses occur within two years after allogeneic stem cell transplantation (allo-SCT). Blinatumomab, an anti-CD19/CD3 bispecific antibody, exerts cytotoxic activity leading to apoptosis of CD19 positive B cells. Blinatumomab and DLI combination therapy is a promising new concept in cancer treatment, whereby blinatumomab might achieve an initial reduction in ALL tumor burden using T-cells, and after tumor clearance, DLI can potentially stimulate the donor immune system to achieve longer lasting remission. Methods: Literature search was performed using PubMed, EMBASE, Cochrane and Web of Science databases up to 3 July 2018. MeSH terms and keywords of blinatumomab, DLI and ALL were used. Results: Comprehensive search retrieved over 150 articles. After exclusion criteria were applied, three studies (n=15 patients) met our inclusion criteria. We summarized data on 15 patients (table 1). Outcomes were not reported homogeneously. Two studies (Ueda, M. et al. 2016; Paul, S. et al. 2017) reported CR in months and one study (Bondarenko, SN. et al. 2017) reported the response rate (RR). Before starting blinatumomab therapy, 12 patients had post-transplant bone marrow relapse, 1 patient had an extramedullary relapse and 2 patients had a minimal residual disease (MRD) without marrow relapse. Total cycles of blinatumomab ranged from 2 to 4. Total cycles of DLI ranged from 1 to 2 given after at least one cycle of blinatumomab. DLI was mostly given with blinatumomab during cycle 3 (ranged from cycle 2 to cycle 4). Blinatumomab doses were not uniformly reported. DLI doses varied between 1x107 and 5x107. Complete remission (CR) with MRD negative status was achieved after 2 cycles of blinatumomab in 3 patients, 2 of them remained in CR for 7 and 13 months. One patient achieved CR and negative MRD status 7 months after initiation of blinatumomab (total cycles of combination therapy=2). Ten patients who had median number of 2 cycles of blinatumomab showed RR of 70%. Grade I acute skin GVHD was reported in one patient during the cycle 3 of blinatumomab before the first combination therapy. One patient developed grade II aGVHD after the combination therapy (cycles were not reported). One patient developed GVHD involving mouth and skin during the second cycle of combination therapy (cycle 3). Grade 3 late-onset acute skin and gut GVHD were reported in one patient after the first dual therapy (cycle 3). No fatalities were observed with combination therapy. Therapy was stopped in one patient who had isolated central nervous system (CNS) relapse detected in the cerebral spinal fluid and orbit following allo-SCT; the patient was treated with intrathecal chemotherapy and radiation. One patient died of extramedullary and hematologic relapses seen at 6 and 11 months after initiating blinatumomab, respectively. This patient previously had a marrow relapse before starting therapy. One patient having an extramedullary disease progressed despite blinatumomab and DLI. Conclusion: Blinatumomab and DLI combination therapy appears to be safe and effective, specially for patients with MRD positive status after stem cell transplantation. Large prospective studies are required to completely understand the efficacy and safety of this combination therapy. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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  • 4
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 1948-1948
    Abstract: BACKGROUND: Despite recent advancements in treatment for multiple myeloma (MM) there is a constant need for newer therapies to tackle the complex issue of relapse and therapy after relapse for patients with MM. Ibrutinib is an oral inhibitor of Bruton tyrosine kinase (BTK), which is overexpressed in the plasma cells. We conducted a comprehensive literature search to analyze the efficacy, dosing and toxicity profile of ibrutinib in relapsed MM. METHODS: Database search using PubMed, EMBASE, Cochrane Library, Web of Science and Clinicaltrials.gov was performed on 06/05/18 (last update) . All clinical trials that used ibrutinib either as monotherapy or in combination regimens in the setting of relapsed and refractory multiple myeloma (RRMM) were included. RESULTS: A total of 388 articles were found on the initial search and after screening, three phase I and II clinical trials qualified for inclusion. Ibrutinib based regimen data (n=155 patients) was analyzed (Table 1). Majority (68%) of the patients were refractory to their previous line of therapy. Ibrutinib Monotherapy: Monotherapy (n=31) with a dose of 420 mg/d to 840 mg/d demonstrated a 0% ORR (overall response rate). A median PFS (progression-free survival) of 0.9 to 2.8 months was noticed with ibrutinib monotherapy. Most common hematological adverse events (HAE) noted were anemia (32%), thrombocytopenia (29%) and neutropenia (13%). All-grade gastrointestinal disturbances (GI) were observed in 90% of cases, fatigue and respiratory infections (RI), each in 39% and muscle spasms in 23% of cases. Ibrutinib + Dexamethasone: The addition of 40 mg dexamethasone to 560 mg/d (n=18) and 840 mg/d (n=43) ibrutinib showed an ORR of 6% and 5% and reported median PFS of 3.7 months and 4.6 months, respectively. Side effects included anemia (26%), thrombocytopenia (23%), and neutropenia (2%). GI toxicity was noted in 82% patients, fatigue in 46%, RI in 15% and muscle spasms reported in 15% patients. Ibrutinib + Carfilzomib: At 560 mg/d dose of ibrutinib, the addition of 27 mg/m2 (n=3) and 36 mg/m2 of carfilzomib (n=5) showed a response of 67% and 40%, respectively. The best response was elicited when 20 mg of dexamethasone was added to 36 mg/m2 of carfilzomib and ibrutinib at a dose of 840 mg/d (n=18; ORR: 71%) and 560 mg/d (n=17; ORR: 71%). The median duration of responses was 12.9 months. Minimal responses were observed in an additional 4 patients giving an overall clinical benefit rate of 76%. At a dose of 36 mg/m2 of carfilzomib, median PFS was reported as 8.1 and 6.4 months at 560 mg/d and 840 mg/d doses of ibrutinib, respectively. Most common HAE were anemia (35%), thrombocytopenia (28%) and neutropenia (9%). Eighty-six percent of patients developed GI disturbances while fatigue and muscle spasms were noted in 53% and 19%, respectively. RI were observed in 51% of patients. Ibrutinib + Bortezomib: The combination of ibrutinib given at 840 mg/d dose with a twice weekly dose of bortezomib 1.3 mg/m2 elicited a response in 46% (n=20) patients, and minimal responses in 4 (21%) patients. Most common GI disturbance was diarrhea (50%). Upper respiratory infections were noted in 30% cases while, asthenia and peripheral edema seen in 20% of cases. Bortezomib/IMiD Refractory Cohort: Patients refractory to prior bortezomib (n=27) showed an encouraging ORR of 73% that was durable for a median of 9.1 months when ibrutinib+carfilzomib+dexamethasone regimen was used. Similarly, another cohort (n=25) of double refractory patients treated with a combination of ibrutinib and dexamethasone demonstrated minimal response in 4 (16%) and disease stabilization in another 5 (20%) patients. High-Risk Cohort: In a population of high-risk cytogenetics (del 17p and/or t[4;14]; n=11) treated with 560 mg/dl to 840 mg/dl of ibrutinib, 36 mg/m2 of carfilzomib and (+/-) 20 mg of dexamethasone showed an ORR of 78%, response was durable for a median of 9.1 months, and achieved a median progression free survival (PFS) of 8.1 months . CONCLUSION: Ibrutinib has demonstrated a promising efficacy (70-80% of ORR in combination regimens) along with an acceptable toxicity profile in the heavily pre-treated and dual drug refractory MM patients. Larger prospective clinical trials are needed to further evaluate its efficacy. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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  • 5
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 2194-2194
    Abstract: Background: Sickle cell disorder (SCD) and transfusion dependent beta-thalassemia (TDT) are inherited disorders of β-globin genes leading to ineffective erythropoiesis, hemolysis and multi-organ damage. Though allogenic hematopoietic cell transplantation (allo-HCT) in the only potentially curative therapy, lack of full HLA-matched donor, increased risk of myeloablative conditioning (MAC) regimen related toxicity, poor prognosis in older age groups ( 〉 14 years), and a high risk of infections and graft versus host disease (GVHD) culminating into a high transplant related mortality (TRM) preclude HCT as a treatment option for many patients. Gene therapy has been proposed as a relatively new treatment option for these monogenic disorders. It involves transfection of harvested CD34+ hematopoietic stem cells (HSC) with viral vector to transfer a normal beta globin gene, which are then transplanted back to the autologous donor. However, the available data on gene therapy is extremely variable. The purpose of this review is to evaluate the risks and outcomes of SCD and TDT patients undergoing gene therapy. Methods: A systematic search of databases using PubMed, Embase, Web of science, Cochrane database and Clinicaltrials.gov was performed on with no restrictions of language or time period. A total of 4312 articles were identified and after duplicates removal, 3508 articles were screened for relevance. Clinical studies reporting the most recent follow up results about the efficacy and safety of gene therapy in patients with hemoglobinopathies were considered for inclusion. Their quality assessment was done using the Cochrane tool, and bias was evaluated regarding the study selection, performance, detection, attrition and the reporting of the clinical trials. RESULTS (table-1): Only 7 articles qualified for the strict selection criteria with an N of 47: six studies were phase I trials (Cavazzana, M. et al 2010, Boulad, F. et al 2013, Marktel, S. et al 2017, Kwiatkowski, J. et al 2017, Cavazzana, M. et al 2017, Kanter, J. et al 2017) and one was a phase III trial (Walters, M. et al 2017). Thirty five patients (74.4%) had TDT while 12 patients (25.5%) had SCD. All these patients did not have a suitable HLA-matched HCT donor. The length of follow up was heterogeneous owing to the step wise enrollment of participants and ranged from 2-36 months. Except for 4 cases, the age of included population was 〉 13 years. Lentivirus BB305 encoding the HbAT87Q globin gene was used for gene delivery in 81% patients (n=38). The normal beta globin gene was transduced in remaining 9 TDT cases and it involved transduction using TNS 9.3.55 vector in two cases and with GLOBE lentivirus in 7 cases. MAC with busulfan was used in 81% cases (n=38), while treosulfan+thiotepa was used in 7 cases. The non-myeloablative (NMA) conditioning with busulfan was used in only 2 cases (both TDT). Bone marrow harvest was the source of HSCs in all SCD cases. Except for 3 SCD cases in HGB-204 trial and 3 TDT cases in HGB-207 which measured the potential improvement in outcome by an increase in DP-VCN, the range of drug vector copy number (DP-VCN) was 0.3-1.5 copies per diploid genome. The total hemoglobin (HB) level at last follow up was reported for 62% cases (n=29) and it was 〉 8.8 g/dl in all cases. Twenty-one (60%) thalassemia cases were in a transfusion (Tx) free state at last follow up, including the 7 cases (20%) who developed a complete independence from transfusions. No such Tx-free state was noted in SCD cases although they developed a reduction in the Tx-requirement and 75% SCD cases (n=9) had a 30-100% reduction in the frequency of VOCs. All the cases were alive at their recent follow up with manageable toxicity form conditioning. Acceptable safety until the median follow-up from the 7 trials was established in all cases, with no reported development of post-treatment leukemia or new malignancy in these trials. DISCUSSION: In this largest series of gene therapy for the treatment of hemoglobinopathies (to our knowledge), we find it to be clinically effective in terms of reduction in transfusion needs; data to suggest an improved OS and disease free survival is promising, however long term data is awaited. Gene therapy appears to bypass the limitations faced by allo-HCT especially a high early TRM. Randomized trials reporting the efficacy and safety outcomes with longer follow ups are urgently required. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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  • 6
    In: Frontiers in Public Health, Frontiers Media SA, Vol. 11 ( 2023-9-7)
    Abstract: The taboo of menstruation, lack of discussion on puberty, misinformation and poor awareness on menstrual hygiene management and limited access to safe menstrual products can negatively impact the physical and mental health of women and girls residing in low middle income countries. Aim The aim of the study was to explore the experiences, awareness, perceptions and attitudes of women and girls towards menstrual hygiene management in Pakistan. Moreover, the study also assessed consumer satisfaction towards locally manufactured organic menstrual products. Methods A descriptive cross-sectional study design was used with a sample of 400 women and girls selected through convenience sampling from high schools, universities, outpatient department and gynaecological clinics located in 2 cities, i.e., Islamabad and Rawalpindi, Pakistan. A pre-structured questionnaire was used to explore experiences, awareness, perceptions and attitudes of women and girls towards menstrual hygiene management. Moreover, each respondent was provided with sample of locally designed and manufactured organic menstrual hygiene & amp; wellness kit by a group of women researchers named “FemPure” including organic sanitary pads, feminine wellness mist and feminine wellness wash. The respondents were asked to use the products and a telephonic follow-up was conducted to assess consumer satisfaction for the products after a period of 1 month. Data was analyzed statistically using SPSS 21. Results The results of the study reported that 86.2% ( n  = 345) of the respondents had normal periods. Out of 400 respondents, 58.5% ( n  = 234) knew about any health conditions related to abnormal menstrual cycle while 88.3% ( n  = 353) were aware of female menstrual hygiene. Majority of the respondents 78.7% ( n  = 315) felt ashamed while buying sanitary pads. Out of 400 respondents, 5.4% ( n  = 22) were interested in getting awareness regarding menstrual hygiene. The results of the study showed that all the respondents (100%, n  = 400) were satisfied with FemPure organic menstrual products. Conclusion The study concluded that majority of women and girls faced menstrual hygiene issues during and after the cycle and were eager to receive information on MHM and use organic rash free menstrual wellness products which could be ordered via mobile app. The respondents were satisfied after the use of FemPure organic menstrual products.
    Type of Medium: Online Resource
    ISSN: 2296-2565
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
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  • 7
    In: Nature, Springer Science and Business Media LLC, Vol. 621, No. 7977 ( 2023-09-07), p. E7-E26
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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    detail.hit.zdb_id: 1413423-8
    SSG: 11
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  • 8
    In: Nutrients, MDPI AG, Vol. 14, No. 13 ( 2022-06-24), p. 2612-
    Abstract: Severe Acute Malnutrition (SAM) is a serious public health problem in many low- and middle-income countries (LMICs). Therapeutic programs are often considered the most effective solution to this problem. However, multiple social and structural factors challenge the social inclusion, sustainability, and effectiveness of such programs. In this article, we aim to explore how poor and remote households face structural inequities and social exclusion in accessing nutrition-specific programs in Pakistan. The study specifically highlights significant reasons for the low coverage of the Community Management of Acute Malnutrition (CMAM) program in one of the most marginalized districts of south Punjab. Qualitative data are collected using in-depth interviews and FGDs with mothers and health and nutrition officials. The study reveals that mothers’ access to the program is restricted by multiple structural, logistical, social, and behavioral causes. At the district level, certain populations are served, while illiterate, and poor mothers with lower cultural capital from rural and remote areas are neglected. The lack of funding for nutrition causes the deprioritization of nutrition by the health bureaucracy. The subsequent work burden on Lady Health Workers (LHWs) and the lack of proper training of field staff impact the screening of SAM cases. Moreover, medical corruption in the distribution of therapeutic food, long distances, traveling or staying difficulties, the lack of social capital, and the stigmatization of mothers are other prominent difficulties. The study concludes that nutrition governance in Pakistan must address these critical challenges so that optimal therapeutic coverage can be achieved.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 9
    Online Resource
    Online Resource
    HCA Healthcare ; 2021
    In:  HCA Healthcare Journal of Medicine Vol. 2, No. 1 ( 2021-02-26)
    In: HCA Healthcare Journal of Medicine, HCA Healthcare, Vol. 2, No. 1 ( 2021-02-26)
    Type of Medium: Online Resource
    ISSN: 2689-0216
    Language: English
    Publisher: HCA Healthcare
    Publication Date: 2021
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  • 10
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 1951-1951
    Abstract: Introduction: Central Nervous System (CNS) involvement in multiple myeloma (MM) is a rare extramedullary manifestation which occurs in less than 1% of MM cases. The median survival after the diagnosis (Dx) is 1-2 months (M). Literature review revealed us of various treatment modalities i.e. systemic chemotherapy (CT), intrathecal therapy (IT), and radiotherapy (RT). The primary aim of our analysis is to summarize published literature on presentation patterns and review effective management strategies regarding CNS involvement in MM and its outcome. Methods: We performed a systematic review of 2533 articles published from 2005 using five databases (PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov). After a detailed screening, 28 studies were included. Results: A total of 550 patients (pts) data is included. Eighty-eight (16%) pts had CNS involvement at the time of their initial presentation and 462 (84%) pts had disease detected at the time of relapse / refractory (R/R) disease . The median reported follow up, from the time of initial Dx, was 18 months (M) [range (r) = 3.4-75M]. The median age of pts was 58 years (y) (r= 40-71). The clinical presentations were heterogeneous with cranial nerve palsy (21%), headache (17%), confusion (17%), visual disturbances (17%), extremity weakness (9%), cord symptoms (5%) and nausea / vomiting (5%). The CNS region involved was identified in 366 pts: 163 (44.5%) pts had leptomeningeal (LM) involvement, 98 (26.8%) pts had dural (D)/osteodural (OD) involvement, 10 (2.7%) pts had LM + D/OD involvement, 90 (24.6%) pts had intraparenchymal (IP) involvement and 5 (1.4%) pts had LM + IP involvement. Hundred twenty-nine pts had International Staging System (ISS) information availabe at the time of MM Dx, out of which 39 (30%) pts had stage I disease, 32 (25%) pts had stage II disease and 58(45%) pts had stage III disease. The median time ( reported in studies) for CNS involvement after MM Dx ranges from 2.5-122 M in pts who underwent systemic treatment and 7-96 M in patients who underwent stem cell transplant (SCT). Five hundred twelve (93%) pts underwent treatment, out of which 42 (8.2%) pts had IT therapy with methotrexate and/or cytarabine, 44 (8.5%) pts had RT, 170 (33.2%) pts had CT, 103 (20.1%) pts had IT + RT + CT, 77 (15%) pts had RT + CT, 16 (3.1%) pts had IT + RT and 60 (11.7%) pts had IT + CT. One hundred two pts had SCT along with the other therapies. Among the pts who received systemic treatment, 34 patients received therapy with conventional agents (CA), 80 patients received therapy with novel agents (NA), 347 patients were treated with combination therapy of CA and NA. Data regarding the rest 51 patients were not available. Bortezomib (V) based regimens were given in 158 pts; immune-modulators (IMiD) based regimens in 153 pts; vincristine, adriamycin, dexamethasone (VAd) regimen in 21 pts; alkylators in 85 pts; carfilzomib in 7 pts; bendamustine in 5 pts; pomalidomide in 5 pts and daratumumab was given in 2 pts. The mOS in patients who received NA therapy was 4-25 M. The mOS in patients who received CA therapy was 2.7-8 M. The mOS in patients who received both CA and NA was 2-7.4 M. Seventy-five out of 512 patients were evaluated for efficacy, out of which, 30 pts showed complete response (CR), 6 pts showed very good partial response (VGPR), 17 pts showed partial response (PR) and progressive disease (PD) was seen in 22 pts. Death was reported in 370 out of total 550 pts. Conclusion: Our analysis demonstrated that systemic CT with CA & NA, RT and IT therapy either alone or in combination are the currently available strategies employed in treating CNS myeloma. Furthermore, NA therapies have shown an increase in the overall survival i.e. up to 25 months. The IMiD have shown good CNS penetrance [thalidomide (30-40%), lenalidomide (11%) and pomalidomide (39-49%)] and effectiveness in the clearance of myeloma cells from CSF. There is no established standard of care for CNS myeloma. As prognosis remain dismal for such patients, newer innovative approaches need to be tested in clinical trials (use of drugs like thiotepa, IT Daratumomab, combination regimens for IT therapy coupled with CNS penetrating systemic therapy etc.) to improve current treatment outcomes. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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