Subject(s)
Anemia, Sickle Cell , Hematopoietic Stem Cell Transplantation , Multiple Myeloma , Humans , Multiple Myeloma/drug therapy , Hematopoietic Stem Cell Mobilization , Transplantation, Autologous , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Anemia, Sickle Cell/drug therapy , Stem Cell TransplantationABSTRACT
BACKGROUND: KW-2478 is a novel non-ansamycin Hsp90 inhibitor with modest single-agent activity in relapsed/refractory myeloma but which shows synergistic antimyeloma activity with bortezomib (BTZ) in preclinical studies. This study determined the safety, preliminary clinical activity, and pharmacokinetics of KW-2478, an Hsp90 inhibitor, in combination with BTZ in patients with relapsed/refractory multiple myeloma (MM). METHODS: Phase I dose escalation determined the recommended phase II dose (RP2D) of KW-2478 plus BTZ, which was then used during phase II. RESULTS: The maximum tolerated dose was not reached during phase I and the RP2D was KW-2478 175 mg m-2 plus BTZ 1.3 mg m-2 on days 1, 4, 8, and 11 every 3 weeks. In the efficacy evaluable phase I/II population treated at the RP2D (n=79), the objective response rate was 39.2% (95% confidence interval: 28.4-50.9%), clinical benefit rate 51.9% (40.4-63.3%), median progression-free survival 6.7 (5.9-not reached (NR)) months, and median duration of response 5.5 (4.9-NR) months. In the phase I/II safety population (n=95), the most frequently observed treatment-related grade 3/4 adverse events were diarrhoea, fatigue, and neutropenia (each in 7.4% of patients), and nausea and thrombocytopenia (each in 5.3%). CONCLUSIONS: KW-2478 plus BTZ was well tolerated with no apparent overlapping toxicity in patients with relapsed/refractory MM. The antimyeloma activity of KW-2478 in combination with BTZ as scheduled in this trial appeared relatively modest; however, the good tolerability of the combination would support further exploration of alternate dosing schedules and combinations.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Drug Resistance, Neoplasm/drug effects , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Multiple Myeloma/drug therapy , Neoplasm Recurrence, Local/drug therapy , Salvage Therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Bortezomib/administration & dosage , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Maximum Tolerated Dose , Middle Aged , Morpholines/administration & dosage , Multiple Myeloma/pathology , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis , Survival Rate , Tissue DistributionABSTRACT
OBJECTIVE: The aim of this study was to evaluate (a) the surgical outcomes of pectineal ligament hysteropexy (PLH) for uterine prolapse by laparotomy and (b) the feasibility and safety of the procedure by laparoscopic route. METHODS: This is a retrospective consecutive case series of women who underwent PLH from January 1998 to December 2011. The prolapsed uterus was suspended with polyester tape to pectineal ligament on either side through a Cherney incision or laparoscopically at 3 urban and 3 rural hospitals in India. RESULTS: In 194 women who underwent PLH (176 open and 18 laparoscopic), there were no intraoperative complications. The mean follow-up was 6.5 years (range, 0.5-12 years) for open method and 1 year (range, 0.5-2 years) for laparoscopic approach. There were 46 births in 40 women after the procedure including 32 vaginal and 14 cesarean deliveries. Overall, 10 women (5.1%) had uterine prolapse recurrence; 7 of these occurred after vaginal delivery. One woman had tape erosion into the bladder because of pelvic tuberculosis. At follow-up, 12 women developed cystocele, and 7 women developed portio vaginalis elongation. There were no postoperative enteroceles. Overall reoperation rate was 14.9%. Laparoscopic PLH had minimal morbidity with no recurrence over 2 years. CONCLUSIONS: Open PLH for uterine prolapse may be safely performed and gives durable support to the prolapsed uterus with low recurrence risk.
Subject(s)
Gynecologic Surgical Procedures/methods , Laparoscopy/methods , Ligaments/surgery , Premenopause , Uterine Prolapse/surgery , Adult , Cystocele/pathology , Female , Hospitals, Rural , Hospitals, Urban , Humans , India , Retrospective Studies , Young AdultABSTRACT
Therapeutic advances and the availability of novel agents have significantly improved outcomes in myeloma; yet, it remains incurable and strategies to improve survival continue to be sought. One approach is to prolong the duration of response and increase progression-free survival (PFS) through consolidation or maintenance treatment with regimens that have low toxicity profiles, and do not negatively impact on quality of life. Data from several studies with thalidomide, lenalidomide and bortezomib consistently show improvements in response and PFS, although results have still to be confirmed with respect to overall survival (OS). Despite the promising data, the optimal use of consolidation and maintenance treatment in terms of regimen, dose and duration has yet to be defined. Given the evidence to date, the UK Myeloma Forum believes that both maintenance and consolidation therapy should be considered as treatment options for patients with myeloma. Patients should be encouraged to enrol in clinical studies. This document reviews the current position of maintenance and consolidation for patients with myeloma treated in the UK.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Chromosome Aberrations , Consolidation Chemotherapy , Maintenance Chemotherapy , Multiple Myeloma/drug therapy , Boronic Acids/administration & dosage , Bortezomib , Clinical Trials as Topic , Disease Management , Humans , Induction Chemotherapy , Lenalidomide , Multiple Myeloma/genetics , Multiple Myeloma/mortality , Multiple Myeloma/pathology , Pyrazines/administration & dosage , Remission Induction , Survival Analysis , Thalidomide/administration & dosage , Thalidomide/analogs & derivatives , United KingdomABSTRACT
OBJECTIVE: To report on a collective pectineal ligament suspension experience acquired over 12 years in India with 119 women who presented with prolapsed vaginal vault. The feasibility and effectiveness of the procedure was assessed for the open and laparoscopic routes. METHODS: The prolapsed vaginal vault was suspended unilaterally to the pectineal ligament using polyester tape at 3 urban and 3 rural hospitals. The procedure was done through a Cherney incision in 104 women. In the remaining 15 women, it was done laparoscopically at a single urban center. RESULTS: There were no intraoperative complications. The mean follow-up was 5.5 years (range, 0.5-12 years). Only 2 women had vaginal prolapse recurrence, at 3 and 5 years. Two had asymptomatic tape erosion, at 2 and 5 years, and a mild cystocele appeared in 5 women and a low rectocele in 4. However, none of these women required further vaginal surgery during their follow-up period. CONCLUSION: The present study demonstrates the long-term safety and effectiveness of pectineal ligament suspension for vaginal vault prolapse by the open and the laparoscopic routes. As it was done by surgeons of varying experience at centers with varying resources, the procedure can be readily mastered by any gynecologic surgeon.
Subject(s)
Gynecologic Surgical Procedures/methods , Laparoscopy/methods , Pelvic Organ Prolapse/surgery , Adult , Aged , Feasibility Studies , Female , Follow-Up Studies , Gynecologic Surgical Procedures/adverse effects , Gynecologic Surgical Procedures/instrumentation , Humans , India , Ligaments , Middle Aged , Recurrence , Rural Health Services , Surgical Tape , Treatment Outcome , Urban Health ServicesABSTRACT
We describe a new model of myeloma bone disease in which beta2m NOD/SCID mice injected with KMS-12-BM cells develop medullary disease after tail vein administration. Micro-computed tomography analysis demonstrated significant bone loss in the tibiae and vertebrae of diseased animals compared to controls, with loss of cortical bone (P<0.01), as well as trabecular bone volume, thickness and number (P<0.05 for all). Bone marrow of diseased animals demonstrated an increase in osteoclasts (P<0.01) and reduction in osteoblasts (P<0.01) compared to control animals. Both bone loss and osteoclast increase correlated with the degree of disease involvement. Mesenchymal stem cells (MSCs) were lentivirally transduced to express human osteoprotegerin (hOPG). Systemic administration of OPG expressing MSC reduced osteoclast activation (P<0.01) and trabecular bone loss in the vertebrae (P<0.05) and tibiae of diseased animals, to levels comparable to non-diseased controls. Because of its predominantly medullary involvement and quantifiable parameters of bone disease, the KMS-12-BM xenogeneic model provides unique opportunities to test therapies targeted at the bone marrow microenvironment.
Subject(s)
Disease Models, Animal , Lentivirus/genetics , Mesenchymal Stem Cells/cytology , Multiple Myeloma/pathology , Multiple Myeloma/therapy , Osteoprotegerin/biosynthesis , Animals , Bone and Bones/metabolism , Cell Line , Genetic Therapy/methods , Humans , Kinetics , Lentivirus/metabolism , Mesenchymal Stem Cells/metabolism , Mice , Mice, Inbred NOD , Mice, SCID , Neoplasm Transplantation , Osteoblasts/metabolism , Osteoclasts/metabolism , Tibia/pathologyABSTRACT
We report the case of a 46-year-old male who developed dermatomyositis and a sarcoid-like reaction in association with testicular relapse of multiple myeloma. The myositis progressed despite chemotherapy directed at the underlying malignant disorder and immunosuppressive treatment. There was, however, a dramatic and sustained response to high-dose chemotherapy and autologous peripheral blood stem cell transplantation which resulted in resolution of the myopathy and partial resolution of the sarcoid-like reaction. This case report highlights the potential of autologous stem cell transplantation as treatment for para-neoplastic disorders associated with haematological malignancies.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Dermatomyositis/therapy , Hematopoietic Stem Cell Transplantation , Multiple Myeloma/complications , Sarcoidosis/therapy , Combined Modality Therapy , Dermatomyositis/diagnosis , Dermatomyositis/etiology , Humans , Male , Middle Aged , Multiple Myeloma/therapy , Recurrence , Sarcoidosis/diagnosis , Sarcoidosis/etiology , Testicular Neoplasms/therapy , Treatment OutcomeABSTRACT
Being attentive to the educational needs of chronically ill children is a relatively recent development in American education. Advances in medical sciences that have improved survival rates for some conditions and increased public acceptance of people who are different or disabled and legislation that has established education as an entitlement for all children have allowed for the entrance of many chronically ill children into mainstream education. Successful school reentry is essential if the child is to develop normally, in terms of intellect, social skills, and peer relationships. Caregivers must not lose sight of the fact that school provides opportunities for social, emotional, and cognitive development. Thus the pediatric nurse practitioner can promote the benefits gained from schooling in numerous ways and provide the child, family, and school personnel with the support and information needed for a smooth transition back into the school system.