PubMed Health⌕ Search

Biomedical subjects

A Kashyap

Publications and source records attributed to A Kashyap.

At least 19 recordsLinked to original sources
PubMed2000

Multiple sclerosis flares associated with recombinant granulocyte colony-stimulating factor.

Four of 10 patients who were enrolled on protocols of high-dose immunosuppression with peripheral blood stem cell rescue for MS experienced neurologic worsening while receiving recombinant human granulocyte colony-stimulating factor. There was improvement when methylprednisolone was given to three of the patients, but one patient died of respiratory failure. The mechanism of the neurologic worsening is uncertain.

Adult↗
PubMed2000

Predictors of therapy-related leukemia and myelodysplasia following autologous transplantation for lymphoma: an assessment of risk factors.

We analyzed data on 612 patients who had undergone high-dose chemoradiotherapy (HDT) with autologous stem cell rescue for Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) at the City of Hope National Medical Center, to evaluate the incidence of therapy-related myelodysplasia (t-MDS) or therapy-related acute myeloid leukemia (t-AML) and associated risk factors. A retrospective cohort and a nested case-control study design were used to evaluate the role of pretransplant therapeutic exposures and transplant conditioning regimens. Twenty-two patients developed morphologic evidence of t-MDS/t-AML. The estimated cumulative probability of developing morphologic t-MDS/t-AML was 8.6% +/- 2.1% at 6 years. Multivariate analysis of the entire cohort revealed stem cell priming with VP-16 (RR = 7.7, P = 0.002) to be independently associated with an increased risk of t-MDS/t-AML. The influence of pretransplant therapy on subsequent t-MDS/t-AML risk was determined by a case-control study. Multivariate analysis revealed an association between pretransplant radiation and the risk of t-MDS/t-AML, but failed to reveal any association with pretransplant chemotherapy or conditioning regimens. However, patients who had been primed with VP-16 for stem cell mobilization were at a 12. 3-fold increased risk of developing t-AML with 11q23/21q22 abnormalities (P = 0.006). Patients undergoing HDT with stem cell rescue are at an increased risk of t-MDS/t-AML, especially those receiving priming with VP-16 for peripheral stem cell collection. (Blood. 2000;95:1588-1593)

Adolescent↗
PubMed2000

Equivalence of 2 effective graft-versus-host disease prophylaxis regimens: results of a prospective double-blind randomized trial.

We have previously demonstrated a decrease in the incidence of acute graft-versus-host disease (GVHD) with the addition of methotrexate (MTX) to cyclosporine (CSP) and prednisone (PSE) chemotherapy in patients with leukemia. We have now completed a prospective randomized trial comparing the 3-drug regimen (CSP/MTX/PSE, including 3 doses of MTX) to the standard 2-drug regimen (CSP/MTX, including 4 doses of MTX) to investigate the benefit of PSE used up front for the prevention of acute and chronic GVHD. In the trial, 193 patients were randomized and 186 were included in the final analysis. All patients received a bone marrow graft from a fully histocompatible sibling donor. The preparatory regimen consisted of fractionated total-body irradiation (fTBI) and etoposide in all but 13 patients, who received fTBI and cyclophosphamide. The patients were randomized to receive either CSP/MTX/PSE or CSP/MTX. The 2 groups were well balanced with respect to diagnosis, disease stage, age, donor-recipient sex, and parity. In an intent-to-treat analysis, the incidence of acute GVHD was 18% (95% confidence interval [CI] 12-28) for the CSP/MTX/PSE group compared with 20% (CI 10-26) for the CSP/,MTX group (P = .60), with a median follow up of 2.2 years. Overall survival was 65% for those receiving CSP/MTX/PSE and 72% for those receiving CSP/MTX (P = .10); the relapse rate was 15% for the CSP/MTX/PSE group and 12% for the CSP/MTX group (P = .83). The incidence of chronic GVHD was similar (46% versus 52%; P = .38), with a follow-up of 0.7 to 6.0 years. Of interest, 21 patients went off study due to GVHD (5 in the CSP/MTX/PSE group and 16 in the CSP/MITX group [P = .02]), and 11 patients went off study because of alveolar hemorrhage (3 in the CSP/MTX/PSE group and 8 in the CSP/MTX group [P = .22]). The addition of PSE did not result in a higher incidence of infectious complications, bacterial (66% versus 58%), viral (77% versus 66%), or fungal (20% versus 20%), in those receiving CSP/MTX/PSE versus CSP/MTX, respectively. These data suggest that the addition of PSE was associated with a somewhat lower incidence of early posttransplantation complications but did not have a positive impact on the incidence of acute or chronic GVHD or event-free or overall survival.

Acute Disease↗
PubMed2000

Effects of allogeneic bone marrow transplantation on recipient bone mineral density: A prospective study.

Allogeneic bone marrow transplant (BMT) recipients have many known risk factors for developing decreased bone mineral density (BMD) after transplantation. We performed a prospective sequential evaluation of BMD in the lumbar spine and nondominant hip using dual-energy x-ray absorptiometry (DEXA) in a cohort of 47 adult patients (median age, 43 years) who were undergoing radiation-based BMT for hematologic malignancies. Baseline DEXA studies were performed before BMT and repeated at 3 to 4 months, 6 to 8 months, and 12 to 14 months after BMT. The majority of patients (60%) had been minimally treated with combination cytotoxic chemotherapy, having received no more than 1 treatment regimen before BMT. Graft-versus-host disease prophylaxis consisted of cyclosporine in combination with either methotrexate or prednisone, or both. Mean lumbar spine and hip BMD were normal before BMT (spine: 1.01 g/cm2, z score = 96%; hip: 0.86 g/cm2, z score = 100%) and gradually decreased (spine: 0.98 g/cm2, z score = 94%; hip: 0.76 g/cm2, z score = 91%) at 12 to 14 months. These declines were statistically significant (P < .006 and < .002 for lumbar spine; P < .001 and < .001 for hip). In addition, the sharpest decline occurred during the first 6 months after BMT and was more marked in the hip than the lumbar spine. These data suggest that BMT adversely affects BMD in this patient population.

Absorptiometry, Photon↗
PubMed2000

Allogeneic stem cell transplantation (BMT) for AML and MDS following i.v. busulfan and cyclophosphamide (i.v. BuCy).

Pretransplant conditioning therapy with i.v. BuCy followed by allogeneic hematopoietic stem cell transplantation (BMT) was investigated in a phase II trial in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). We gave i.v. Bu at a dose of 0.8 mg/kg every 6h x 16 doses, followed by Cy 60 mg/kg daily for 2 days. Twenty-six AML patients (18 males/eight females) were treated, only eight of whom were in CR1. The rest were either refractory to induction chemotherapy (four patients) or in a more advanced stage of their disease (14 patients). In addition, nine patients with MDS (1M/8F) were treated. Their median age was 41 years (range 21-64). Engraftment to > or =500 neutrophils/microl was reached at 14 days (range 10-29 days) post BMT, and the median time of neutropenia was only 11 days (range 4-28 days). The most common regimen-related toxicity was grade 2-3 nausea. In the post-BMT period (including BMT day +30), two patients died, one each from pulmonary hemorrhage secondary to CMV pneumonia and hepatic veno-occlusive disease (VOD), for an early treatment-related mortality (TRM) of 5.7%. Three patients developed VOD and two of them died. There was no direct regimen-related pulmonary or neurologic toxicity. Overall, the clinical side-effect spectrum was analogous to what would be expected from a high-dose oral Bu-based regimen; there was no unique toxicity experienced with the used solvent system. The disease-free survival in the high-risk subgroup (all patients not in CR1) at 1 and 2 years post transplant was 44% and 31%, respectively. The 13 patients still alive in CR have been followed for a median of 24 months (range 18-32). Pharmacokinetic analysis showed very good interdose reproducibility, and limited interpatient variability in area under the plasma concentration vs time curve, peak concentration, and clearance of Bu after this i.v. formulation. We conclude, that this new i.v. Bu formulation is well tolerated; it has an impressive safety profile, and we suggest that it should be considered as appropriate replacement for oral busulfan in pretransplant conditioning therapy prior to allogeneic BMT for patients with AML or MDS.

Administration, Oral↗
PubMed2000

Acute myoedema: an unusual presenting manifestation of hypothyroid myopathy.

We describe a patient with primary hypothyroidism due to autoimmune thyroiditis, presenting with acute myoedema and spontaneous rhabdomyolysis. During his hospital stay, he developed altered sensorium due to hypo-osmolal hyponatraemia and later developed bilateral foot drop that responded to appropriate treatment.

Acute Disease↗
PubMed1999

High-dose chemo/radiotherapy and autologous bone marrow or stem cell transplantation for poor-risk advanced-stage Hodgkin's disease during first partial or complete remission.

Complete remission rates of 70-90% can be achieved following combination chemotherapy for patients with advanced-stage Hodgkin's disease (HD). Patients who present with unfavorable poor prognostic factors, however, have a 5-year disease-free survival of only 40-50%. In an attempt to improve the prognosis of 20 patients with poor-risk advanced-stage HD, we evaluated the role of early high-dose therapy (HDT) and autologous bone marrow/stem cell transplantation (ASCT) during the first complete or partial remission (CR/PR). Patients were eligible for ASCT if they either achieved a PR (defined as > 50% regression) (six patients), or achieved a CR (14 patients) but had presented with three or more of the following unfavorable features: stage IV disease with bone marrow involvement or > or = 2 extranodal sites of involvement; bulky mass > 10 cm or bulky mediastinal mass > 1/3 of mediastina/thoracic ratio; B symptoms; and elevated serum lactate dehydrogenase (LDH) level. The study included 11 men (55%) and 9 women (45%). The median age was 37 years (range 20-57). Seventeen patients (85%) had stage IV disease; 14 (70%) had B symptoms; 13 (65%) had bulky mass > 10 cm; 14 (70%) had > or = 2 extra nodal sites involvement; and eight patients (40%) had elevated LDH levels. All patients were treated with standard four or 7-8 drug combination chemotherapy regimens until they achieved maximal response prior to ASCT with a median of six cycles (range 4-11). Six patients also received involved field radiotherapy to residual bulky mass > 5 cm or bony lesions before ASCT. The median time from diagnosis to ASCT was 8.6 months (range 5.5-18.9). Preparative regimens consisted of fractionated total body irradiation (FTBI) 1200 cGy in combination with etoposide 60 mg/kg and cyclophosphamide 100 mg/kg in all patients except one who had borderline pulmonary function and received lomustine 15 mg/kg instead of FTBI. All patients engrafted and there was no transplant-related mortality. One patient developed congestive cardiomyopathy at 4 years post-ASCT. All patients remain alive and in remission at a median follow-up of 42.8 months (range, 13.2-149.2). These preliminary results suggest that HDT and ASCT can be performed safely during first CR/PR in selected patients with advanced-stage HD who have an unfavorable prognosis. Further randomized studies comparing HDT and ASCT during first CR with conventional chemotherapy and ASCT at relapse in poor-risk advanced-stage HD should be conducted. The prognostic factors and risk groups described recently by an international prognostic study can be used to identify high-risk patients who may be candidates for more intensive therapy.

Adult↗
PubMed1999

Long-term follow-up of 23 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with allogeneic bone marrow transplant in first complete remission.

Between 1984 and 1997, 23 consecutive patients with Philadelphia chromosome-positive acute lymphoblastic leukemia in first complete remission were treated with allogeneic bone marrow transplants from HLA-matched siblings. All patients but one were conditioned with fractionated total body irradiation (1320 cGy) and high-dose etoposide (60 mg/kg). One patient received high-dose cyclophosphamide instead of etoposide, and another patient received both drugs. Nine patients died following BMT, two from relapsed leukemia, and seven from transplant-related causes. The 3-year probabilities of disease-free survival and relapse are 65% and 12%, respectively. For patients transplanted after 1992, these probabilities are 81% (48-95%, 95% confidence interval) and 11% (2-50%), respectively. The relatively low relapse rate in this group of patients compared to published reports may reflect the enhanced anti-leukemic activity of etoposide in combination with FTBI compared to other conditioning regimens. The enhancement in overall survival for patients transplanted after 1992 may reflect improvements in supportive care, in particular, the prophylaxis of serious fungal and viral infections.

Adult↗
PubMed1999

Interleukin-2-activated autologous bone marrow and peripheral blood stem cells in the treatment of acute leukemia and lymphoma.

In this pilot trial of interleukin (IL)-2-treated autologous bone marrow (BM) and peripheral stem cell (PSC)-supported high-dose chemoradiotherapy, we report 36 patients with poor-prognosis leukemia and lymphoma who received BM and/or granulocyte colony-stimulating factor (G-CSF)-mobilized autologous PSCs that had been exposed to IL-2 for 24 hours ex vivo. Patients then received IL-2 by low-dose continuous intravenous (i.v.) infusion until hematologic reconstitution and then by intermediate-dose continuous i.v. infusion for six 2-week maintenance cycles given at 1-month intervals. The median Day to neutrophils over 500/microL was 22 with BM and 10 with PSCs (p = 0.01). The median Day to platelets >20,000/microL was 50 for BM and 25 for PSCs, and to platelets >50,000/microL was 138 for BM and 34 for PSCs (p not significant). After the first three patients received IL-2 at 2 mIU x m(-2) x day(-1) and had slow reconstitution, four patients were treated without IL-2 until the maintenance phase following reconstitution. The remaining 29 patients received the initial "post-infusion" IL-2 at 1 mIU x m(-2) x day(-1). Toxicities associated with the infusion of IL-2-activated cells consisted of chills and fever in about one-half of the patients and transient hypotension in 12%. Low-dose IL-2 by continuous i.v. infusion in the early posttransplant period was associated with exacerbation of fever, diarrhea, and altered mental status in a minority of patients. The major dose-limiting toxicities of maintenance IL-2 were fever, fatigue, gastrointestinal symptoms, skin rash, and dyspnea. Among 24 lymphoma patients, nine are in continuous complete remission (CCR) from 18-48 months, and 15 have died (12 due to relapse and three of therapy-related toxicities). Of 12 acute leukemia patients, two with acute lymphoblastic leukemia (ALL) are in CCR at 38 and 43 months, and one patient who was in cytogenetic but not molecular remission of Philadelphia chromosome-positive ALL died of progressive leukemia at Day 108. Three of nine with myeloid leukemia are in CCR at 21, 46, and 53 months; one is in hematologic and cytogenetic remission of acute promyelocytic leukemia at 55 months with multiple new cytogenetic abnormalities; one is alive at 54 months with pancytopenia after incomplete hematologic recovery followed by multiple new cytogenetic abnormalities (myelodysplasia); and one had an unrelated donor transplant after relapsing 4 months following protocol therapy. One myeloid leukemia patient remains without evidence of relapse, but is transfusion-dependent at 15 months following transplant.

Acute Disease↗
PubMed1998

Autologous bone marrow transplantation for non-Hodgkin's lymphoma resulting in long-term remission of coincidental Crohn's disease.

Crohn's disease usually runs a chronic relapsing and remitting course, characterized by a repeated need for immunosuppressive drug therapy or often surgery. and is considered to be incurable by standard treatment. We report a case of successful long-term disease control of Crohn's disease following autologous bone marrow transplantation. This case provides further support for the concept that some forms of severe immune-mediated diseases may be amenable to treatment by high-dose therapy with autologous stem cell support.

Adult↗
PubMed1997

Results of high-dose therapy and autologous bone marrow/stem cell transplantation during remission in poor-risk intermediate- and high-grade lymphoma: international index high and high-intermediate risk group.

We have conducted a pilot study to investigate the role of high-dose therapy and autologous bone marrow/stem cell transplantation (ASCT) during first complete or partial remission in 52 patients with poor-risk aggressive lymphoma. There were 42 patients with intermediate-grade or immunoblastic lymphoma who were considered to be high (60%) and high-intermediate risk (40%) groups at diagnosis based on the age-adjusted International Prognostic Index (IPI) and 10 patients with high-grade, SNCCL (small non-cleaved cell, Burkitt's, and non-Burkitt's), who at presentation had poor-risk features defined as elevated serum lactate dehydrogenase level, stage IV, and bulky mass >/=10 cm. The median age was 34 years (range, 16 to 56 years). Thirty-nine were transplanted in first complete remission and 13 in first partial remission after conventional therapy. Conditioning regimens consisted of total body irradiation (TBI) administered as a single fraction 750 cGy in 3 patients and in fractionated doses for a total of 1,200 cGy in 44 patients, in combination with 60 mg/kg etoposide and 100 mg/kg cyclophosphamide. Five patients with prior radiotherapy received 450 mg/m2 carmustine instead of TBI. Stem cell sources were either bone marrow and/or peripheral blood. No in vitro purging was used. All patients engrafted. Two SNCCL patients died of venoocclusive disease at 25 days and acute leukemia at 27 months posttransplantation. There were six relapses at 1.5 to 12.8 months posttransplantation. At a median follow-up of 44 months (range, 1 to 113 months), the estimated 3-year overall survival (OS) and disease-free survival (DFS) for all patients was 84% (95% confidence interval [CI], 70% to 92%) and 82% (95% CI, 68% to 91%), respectively. In the subset of patients with intermediate-grade and immunoblastic lymphoma, the 3-year DFS was 89% (95% CI, 74% to 96%) for all patients, 87% (95% CI, 67% to 96%) for high-risk patients, and 92% (95 CI, 61% to 99%) for high-intermediate risk patients. The 3-year OS and DFS for SNCCL patients were identical at 60% (95% CI, 30% to 84%). These results suggest that high-dose therapy and ASCT during first remission may improve the survival and prognosis of patients with poor-risk intermediate- and high-grade lymphoma. A prospective randomized study comparing high-dose therapy and ASCT with conventional chemotherapy in IPI high-risk patients with aggressive non-Hodgkin's lymphoma should be undertaken.

Adolescent↗
PubMed1996

Modulation of brain catecholamine absorbing proteins by dopaminergic agents.

Catecholamine absorbing proteins (CATNAPs) are localized in the brain and thus far have no known biochemical and pharmacological characteristics consistent with other receptor proteins or metabolic enzymes in the central nervous system. The oxidative metabolism of catecholamines in the brain, especially the catabolism of dopamine and its conjugation with metabolic brain proteins, results in the production of highly toxic free radicals. Since such processes are implicated in the pathophysiology of various neurodegenerative diseases, including parkinsonism, and since CATNAPs bind catecholamines with high affinity, there is a need to further investigate if these novel proteins could play a protective role against these harmful catecholamine metabolites. In this study, we demonstrate the purification, pharmacological characterization and modulation of CATNAPs, as the first steps necessary to elucidate the function of these proteins in the brain. First, CATNAPs were identified from tissues using [3H]N-n-propylnorapomorphine (a specific dopamine receptor agonist) and [125I]6-hydroxy-5-iodo[N(N-2,4-dinitro-phenyl)- aminopropyl]1,2,3,4-tetrahydronaphthalene ([125I]DATN; a highly specific ligand synthesized in our laboratory). Three proteins, with molecular masses of 47, 40 and 26 kDa, were identified and purified, which allowed for the subsequent production of antibodies against each of these CATNAPs. The effects of in vivo chronic administration of several dopaminergic agents on CATNAPs were also examined by Western immunoblotting. L-3,4-Dihydroxyphenylalanine (L-DOPA) treatment in rats resulted in the increase of all of the three proteins, as compared to controls. Treatment in rats with the dopamine depleting agent, reserpine, produced a significant decrease in all of the three CATNAPs. In addition, the effects of direct administration of apomorphine, dopamine, epinephrine, isopropylnorepinephrine, norepinephrine, N-n-propylnorapomorphine and 6-hydroxydopamine on CATNAP levels in rats were examined. Interestingly, we observed an increase (as compared to control) of the 47, 40 and 26 kDa proteins in animals treated with dopamine, norepinephrine, N-n-propylnorapomorphine and apomorphine. In contrast, animals treated with 6-hydroxydopamine showed significant decreases in the levels of all three proteins. It is evident that as the concentration of catecholamines increases, there is a corresponding increase in the levels of CATNAPs in the brain. These results clearly demonstrate the pharmacological modulation of CATNAPs by dopaminergic agents and suggest their possible role in the cytoprotection against damage caused by free radicals generated by oxidative stress.

Adrenergic Uptake Inhibitors↗
PubMed1996

Polymyositis as a manifestation of chronic graft-versus-host disease.

A syndrome indistinguishable from idiopathic polymyositis occurred in 11 patients as a manifestation of chronic GVHD. All patients had elevation of creatine phosphokinase (CPK). Immunohistology demonstrated the effector cells in the muscle infiltrates as cytotoxic T cells, a finding similar to idiopathic polymyositis. Polymyositis is a rarely reported complication of chronic graft-versus-host disease (GVHD) with only 8 cases described in the literature. We encountered this syndrome in a small but significant percentage of our patients with chronic GVHD. Polymyositis associated with chronic GVHD does not affect the overall prognosis for the patient. Moreover, polymyositis can be the only manifestation of chronic GVHD. Awareness of this complication is important because it can be confused with other causes of muscle weakness after bone marrow transplantation. Finally, prompt initiation of corticosteroid therapy results in a rapid improvement of the associated symptoms.

Adolescent↗
PubMed1995

Thalidomide as salvage therapy for chronic graft-versus-host disease.

Thalidomide has been reported to be an effective agent for treatment of chronic graft-versus-host disease (CGVHD). To determine the efficacy of this agent in patients with refractory CGVHD a total of 80 patients who failed to respond to prednisone (PSE) or PSE and cyclosporine (CSA) were treated with thalidomide. Sixteen patients (20%) had a sustained response, 9 with a complete remission and 7 with a partial response. Twenty-nine patients (36%) had thalidomide discontinued because of side effects, which included sedation, constipation, neuritis, skin rash, and neutropenia. Side effects were reversible with drug discontinuation except for mild residual neuritis in one case. Rashes and neutropenia have not previously been reported as thalidomide side effects when used for CGVHD treatment. We conclude thalidomide is immunosuppressive and active in the treatment of CGVHD. A high incidence of reversible side effects limited dose intensity and reduced the number of patients who could benefit from treatment.

Adolescent↗