High-Dose Therapy and Autologous Hematopoietic Cell Transplantation in Peripheral T Cell Lymphoma (PTCL): Analysis of Prognostic Factors

Patients with peripheral T cell lymphoma (PTCL) have a poor prognosis with current treatment approaches. We examined the outcomes of high-dose therapy (HDT) and autologous hematopoietic cell transplant (AHCT) on the treatment of PTCL and the impact of patient/disease features on long-term outcome. Sixty-seven patients with PTCL–not otherwise specified (n = 30), anaplastic large cell lymphoma (n = 30), and angioimmunoblastic T cell lymphoma (n = 7) underwent HDT/AHCT at the City of Hope. The median age was 48 years (range: 5-78). Twelve were transplanted in first complete remission (1CR)/partial remission (PR) and 55 with relapsed or induction failure disease (RL/IF). With a median follow-up for surviving patients of 65.8 months (range: 24.5-216.0) the 5-year overall survival (OS) and progression-free survival (PFS) were 54% and 40%, respectively. The 5-year PFS was 75% for 1CR/PR compared to 32% for RL/IF patients (P = .01). When the Prognostic Index for PTCL unspecified (PIT) was applied at the time of transplant, patients in the PIT 3-4 group had 5-year PFS of only 8%. These results show that HDT/AHCT can improve long-term disease control in relapsed/refractory PTCL and that HDT/AHCT should ideally be applied either during 1CR/PR, or as part of upfront treatment. More effective and novel therapies are needed for patients with high-risk disease (PIT 3-4 factors) and allogeneic HCT should be explored in these patients

WMAP constraints on inflationary models with global defects

We use the cosmic microwave background angular power spectra to place upper limits on the degree to which global defects may have aided cosmic structure formation. We explore this under the inflationary paradigm, but with the addition of textures resulting from the breaking of a global O(4) symmetry during the early stages of the Universe. As a measure of their contribution, we use the fraction of the temperature power spectrum that is attributed to the defects at a multipole of 10. However, we find a parameter degeneracy enabling a fit to the first-year WMAP data to be made even with a significant defect fraction. This degeneracy involves the baryon fraction and the Hubble constant, plus the normalization and tilt of the primordial power spectrum. Hence, constraints on these cosmological parameters are weakened. Combining the WMAP data with a constraint on the physical baryon fraction from big bang nucleosynthesis calculations and high-redshift deuterium abundance, limits the extent of the degeneracy and gives an upper bound on the defect fraction of 0.13 (95% confidence).Comment: 10pp LaTeX/RevTeX, 6 eps figs; matches accepted versio

Kidney Transplantation in Patients With Active Multiple Myeloma: Case Reports.

Kidney disease is a common complication in patients with multiple myeloma. Traditionally, patients with active multiple myeloma and end-stage renal disease have been excluded from kidney transplantation due to the risk of malignancy progression. The introduction of bortezomib-based therapy for patients with multiple myeloma and renal impairment has significantly improved survival in this population. In this report, we present 2 cases of patients with active and controlled multiple myeloma who underwent successful kidney transplantation without progression of their underlying malignancy. In patients with active multiple myeloma controlled with bortezomib, kidney transplantation should be considered a valid option for patients with end-stage kidney disease

Kidney Transplantation in Patients With Active Multiple Myeloma: Case Reports

Abstract. Kidney disease is a common complication in patients with multiple myeloma. Traditionally, patients with active multiple myeloma and end-stage renal disease have been excluded from kidney transplantation due to the risk of malignancy progression. The introduction of bortezomib-based therapy for patients with multiple myeloma and renal impairment has significantly improved survival in this population. In this report, we present 2 cases of patients with active and controlled multiple myeloma who underwent successful kidney transplantation without progression of their underlying malignancy. In patients with active multiple myeloma controlled with bortezomib, kidney transplantation should be considered a valid option for patients with end-stage kidney disease

Health Care Utilization and Cancer Incidence Following Solid Organ Transplant

Background/Aims: Population-based registry studies have found increases in lung, kidney, skin and thyroid cancers among organ transplant recipients compared with the general population. These studies link data from national transplant services and state cancer registries, thereby limiting the ability to describe recommended health care utilization, including preventive services (e.g. influenza vaccinations) and outpatient visits (9 within transplant year), and incident diagnoses of hypertension and diabetes (estimated to be 50% and 18%, respectively). The goal of this study was to characterize health care utilization and cancer incidence among solid organ transplant recipients in Kaiser Permanente Southern California (KPSC). Methods: KPSC transplant registry data was linked to electronic medical records on solid organ transplants from 1990 to 2014. Data was stratified by kidney, liver, heart and lung transplants. Results: Among 4,336 transplant recipients, 62% (2,703/4,336) were white, 80% (3,621/4,336) were \u3e 35 years old, 27% (1,158/4,336) were past smokers and the mean membership length was 5.6 years. Past smoking was highest for lung transplant recipients (34%, 63/185) and liver transplant recipients (33%, 418/1,271). Survival among all transplant recipients was 89% at 2 years posttransplant yet decreased to 65% at 10 years, with the lowest survival among lung recipients (35% at 10 years). Within the first year posttransplant, recipients had a mean number of 5 primary care visits, 7 nephrology visits and 2 visits each for dermatology, urology, and obstetrics and gynecology (women). Influenza vaccination rates have increased over time and were as high as 96% among lung recipients during the 2014-2015 influenza season. Roughly, 12% (322/2,601) and 14% (151/1,082) of transplant recipients had an incident diagnosis of hypertension and diabetes. Finally, there was increased risk of all cancers excluding nonmelanoma skin cancer (standardized incidence ratio: 2.15, 95% confidence interval: 1.93–2.39), with the largest incidence for non-Hodgkin’s lymphoma, lung cancer and kidney cancer. Conclusion: Transplant recipients in KPSC met the recommended number of outpatient visits, including specialty care visits, within the first year posttransplant. Incidences of hypertension and diabetes were lower than expected, and influenza vaccination rates were high. There was a twofold increase in cancer incidence among the solid organ transplant population

Route Design and Development of a MET Kinase Inhibitor: A Copper-Catalyzed Preparation of an <i>N</i>1<i>-</i>Methylindazole

The synthesis of a MET kinase inhibitor in an overall yield of 22% was achieved over eight steps starting with 3-hydroxybenzaldehyde, an improvement from the initial 12-step process with a 5.4% yield. Highlights of the process chemistry design and development are a Cu-catalyzed cyclization to form an important <i>N</i>1-methylindazole ring, a selective nitro reduction in the presence of an aryl bromide, a late-stage Suzuki cross-coupling, and a base-promoted Boc deprotection to form the desired drug candidate

Sequential Bortezomib, Dexamethasone, and Thalidomide Maintenance Therapy after Single Autologous Peripheral Stem Cell Transplantation in Patients with Multiple Myeloma

We report feasibility and response results of a phase II study investigating prolonged weekly bortezomib and dexamethasone followed by thalidomide and dexamethasone as maintenance therapy after single autologous stem cell transplantation (ASCT) in patients with multiple myeloma. Within 4 to 8 weeks of ASCT, patients received weekly bortezomib and dexamethasone for six cycles, followed by thalidomide and dexamethasone for six more cycles. Thalidomide alone was continued until disease progression. Forty-five patients underwent ASCT. Forty patients started maintenance therapy; of these, 36 patients received four cycles, and 32 completed six cycles of maintenance bortezomib. Of these 40 patients, nine (22%) were in complete response (CR) before ASCT, 13 (32%) achieved CR after ASCT but before bortezomib maintenance therapy, and 21 (53%) achieved CR after bortezomib maintenance therapy. Nine patients not previously in CR (33%) upgraded their response to CR with bortezomib maintenance. At 1 year post-ASCT, 20 patients achieved CR, and two achieved very good partial response. Twenty-seven patients experienced peripheral neuropathy during bortezomib therapy, all grade 1 or 2. Our findings indicate that prolonged sequential weekly bortezomib, dexamethasone, and thalidomide maintenance therapy after single ASCT is feasible and well tolerated. Bortezomib maintenance treatment upgraded post-ASCT CR responses with no severe grade 3/4 peripheral neuropathy