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Biomedical subjects

R Chopra

Publications and source records attributed to R Chopra.

At least 91 records · Page 5Linked to original sources
PubMed1992

Mini-BEAM followed by BEAM and ABMT for very poor risk Hodgkin's disease.

High dose chemotherapy and autologous bone marrow transplantation (ABMT) is an effective form of salvage therapy in patients with relapsed or resistant Hodgkin's disease. Patients with large tumour masses at the time of ABMT have a poorer prognosis and we have therefore administered intermediate dose BCNU, etoposide, cytarabine and melphalan (mini-BEAM) prior to high dose therapy with the same agents (BEAM) and ABMT in such patients. In addition we have used the same strategy in patients with bone marrow infiltration at the time of relapse in an attempt to clear the bone marrow for transplant. A total of 23 patients received mini-BEAM and 21 proceeded to BEAM and ABMT. Platelet engraftment was delayed compared to BEAM recipients who had not received mini-BEAM (P = 0.008) but there was only one procedure related death. Responses to BEAM and ABMT were not predicted by the response to mini-BEAM indicating a dose response effect at the upper end of the dose intensity spectrum. At 2 years, the overall survival and progression free survival are 61% and 46% respectively for this group of Hodgkin's patients with extremely poor prognosis.

Adult↗
PubMed1992

The effect of macrophage colony-stimulating factor on haemopoietic recovery after autologous bone marrow transplantation.

Macrophage colony-stimulating factor (M-CSF) is active in the late stages of monocyte maturation, activates mature monocyte-macrophages and enhances their production of various other cytokines. We have examined the effects of a 21 d course of escalating doses of M-CSF purified from human urine (hM-CSF) on recovery following autologous bone marrow transplantation (ABMT) in 20 patients with malignant lymphomas. Four patients were treated at each dose level of 4, 8, 16, 32 and 64 x 10(6) U/m2/d and results compared to 46 concurrent controls. There was no significant difference in recovery to an absolute neutrophil count (ANC) of 0.5 x 10(9)/l (median 20 d in hM-CSF group versus 22 in controls) or in recovery of platelets to 50 x 10(9)/l (32 d versus 39 d, 0.05 less than P less than 0.1); hM-CSF patients received a median of 81 platelet units following ABMT (controls 112 units, P = NS). hM-CSF patients had a median of 5.5 d with fever greater than 37.5 degrees C (control 8, P = NS), received parenteral antibiotics for 14.5 d (control 17, P = NS) and had a 50% incidence of bacteraemia (control 48%). hM-CSF treated patients were discharged by a median of day 29 following transplantation (control 33, P less than 0.05). Platelet and neutrophil recovery correlated significantly with the number of marrow mononuclear cells (MNC) reinfused in the hM-CSF group (P = 0.05 and P = 0.014 respectively) but not in controls. Subgroup analysis showed that hM-CSF patients receiving greater than 2 x 10(8) MNC/kg body weight reached an ANC of 0.5 x 10(9)/l by a median of day 16.5 (control 18.5, NS), became platelet transfusion independent by day 17 (control 29, P less than 0.05) and reached a platelet count of 50 x 10(9)/l by day 21 (control 40, P less than 0.05). No significant toxicity attributable to hM-CSF treatment was seen. These results suggest that hM-CSF accelerates platelet recovery following ABMT and that relatively large marrow innocula are required to see this effect.

Adult↗
PubMed1992

Triglyceride fatty acid chain length influences the post prandial rise in serum intestinal alkaline phosphatase activity.

Intestinal alkaline phosphatase (IALP) activity rises following the ingestion of a fat-containing meal. Previous studies on intestinal fluid and lymph have shown that the magnitude of this response is dependent upon fatty acid chain length. To examine this relation in the serum of healthy humans, 10 subjects consumed two standardized fat meals. One meal contained predominantly long chain fatty acid triglycerides, the other contained predominantly medium chain fatty acid triglycerides. Serum IALP activity was measured in serial blood samples using a sensitive immunological assay. IALP activity was ABO blood group and secretor status dependent. The post-prandial rise in serum IALP activity was significantly greater following the long chain fatty acid meal than following the medium chain fatty acid meal. Previous observations of the fatty acid chain length dependency of the IALP response to fat ingestion, therefore, also apply in the serum of healthy humans under normal physiological conditions. Standardized fat meals provide the basis of a useful method for the investigation of the role of IALP in fat absorption.

ABO Blood-Group System↗
PubMed1992

Autologous versus allogeneic bone marrow transplantation for non-Hodgkin's lymphoma: a case-controlled analysis of the European Bone Marrow Transplant Group Registry data.

PURPOSE: A case-controlled study of patients who reported to the European Bone Marrow Transplant Group (EBMTG) was performed to investigate the relative roles and efficacy of allogeneic (alloBMT) and autologous bone marrow transplantation (ABMT) in non-Hodgkin's lymphoma. PATIENTS AND METHODS: Of 1,060 patients who reported to the lymphoma registry, 938 patients underwent ABMT and 122 patients underwent alloBMT. A case-controlled study was performed by matching 101 alloBMT patients with 101 ABMT patients. The case matching was performed after the selection of the main prognostic factors for progression-free survival by a multivariate analysis. RESULTS: The progression-free survival was similar in both types of transplants (49% alloBMT v 46% ABMT). The overall relapse and progression rate for the alloBMT patients was 23% compared with 38% in the ABMT patients. This difference was not significant statistically. In the lymphoblastic lymphoma subgroup, alloBMT was associated with a lower relapse rate than ABMT (24% alloBMT v 48% ABMT; P = .035). The progression-free survival, however, was not significantly different because patients with lymphoblastic lymphoma who underwent alloBMT had a higher procedure-related mortality (24% alloBMT v 10% ABMT; P = .06). A significantly lower relapse/progression rate was also observed in patients with chronic graft-versus-host disease (cGVHD) compared with those patients without (0% cGVHD v 35% no cGVHD; P = .02). Fourteen of 18 patients who had cGVHD also had lymphoblastic lymphoma. CONCLUSION: This study suggests that ABMT and alloBMT for non-Hodgkin's lymphoma are comparable, with the exception of lymphoblastic lymphoma in which a graft-versus-lymphoma effect may account for the lower relapse rate for patients who underwent alloBMT.

Adolescent↗
PubMed1992

Successful treatment of fungal infections in neutropenic patients with liposomal amphotericin (AmBisome)--a report on 40 cases from a single centre.

The use of high-dose chemotherapy and the subsequent prolonged neutropenia in patients with haematological diseases has resulted in an increased incidence of fungal infections. The only drug with proven efficacy in the treatment of deep seated fungal infections or invasive aspergillosis is amphotericin B. Unfortunately, this drug has adverse side effects, most importantly dose dependent nephrotoxicity. Furthermore, some patients fail to show a response to amphotericin B. We have treated 40 patients undergoing myeloablative chemotherapy and or bone marrow transplantation for haematological diseases with liposomal amphotericin for proven or suspected fungal infections. All patients had failed treatment with conventional Amphotericin B. Fourteen patients received liposomal amphotericin (AmBisome) due to progression of infection on conventional amphotericin B. Twenty six patients received liposomal amphotericin due to nephrotoxicity caused by conventional Amphotericin B. Nine patients had mycologically proven fungal infection and of these, 7 patients (78%) showed a complete response to liposomal amphotericin. Thirty one patients received liposomal amphotericin due to suspected fungal infection. Eleven of these 31 patients (35%) showed a complete clinical response to liposomal amphotericin. However in the patients with suspected fungal infections 14 patients had no response and 6 patients could not be evaluated for response to liposomal amphotericin. Overall, of the 18 patients showing a response to liposomal amphotericin, 15 patients had either recovered their neutrophil count (> 0.5 x 10(9)/l) or achieved remission from their underlying haematological disease. Recovery from fungal infection in this group of patients occurred when there was complete remission of underlying disease and recovery of neutrophil counts, when concurrently treated by liposomal amphotericin.

Adolescent↗
PubMed1992

von Willebrand factor as a marker of endothelial cell activation following BMT.

Endothelial cell activation may play a role in thrombotic complications of BMT such as hepatic veno-occlusive disease (VOD), right atrial line thrombosis and microangiopathic haemolysis. To assess this, von Willebrand factor antigen (vWF:ag) was measured in 72 patients (25 allografts, 46 autografts and one syngeneic) during the first 6 weeks post-transplant. There was a significant rise in vWF:ag in both allografts and autografts but a greater increase was seen in the allografts. The changes in vWF:ag did not correlate with changes in C reactive protein showing that this was not merely an acute phase response. vWF multimers were normal in a subgroup of uncomplicated transplants showing that there was no large scale endothelial cell disruption. Patients with VOD did not have changes in vWF:ag that were consistently different from uncomplicated controls. Three of four patients who developed line thrombosis had higher levels of vWF:ag compared with control groups; multimeric structure of the vWF was again normal. These results show that there is endothelial cell activation post-BMT and that this is greater in allografts compared with autografts, thus suggesting a possible mechanism for the higher incidence of VOD in this group. There were no useful predictive markers of VOD or thrombosis in individual patients.

Adolescent↗
PubMed1991

Differential effects of concanavalin A, serum and cytokines on proteoglycan elaboration and DNA synthesis by mononuclear cells from human peripheral blood.

Human blood derived mononuclear cell (MC) cultures required concanavalin A (Con A) stimulation to synthesize and secrete into the medium high levels of a protease-resistant proteoglycan (PG) containing predominantly chondroitin sulfate (CS), which was elaborated largely by T-cells in culture. PG and DNA synthesis were studied in MC cultures in the absence and presence of Con A as well as serum and some biologically active polypeptide factors. In the presence of Con A, stimulation of PG synthesis was substantially greater in T-cell enriched cultures than in B-cell enriched cultures. DNA synthesis was also stimulated in the presence of Con A. This stimulation was concentration-dependent, but required the presence of serum for additional responses. DNA and cell proliferation were stimulated by interleukin-2 (IL-2), but PG production was not stimulated by conditioned media, IL-1, IL-2, IL-3, or transforming growth factor-beta (TGF-beta). Our results indicate that the elaboration of PG from T-cells of human MC is independent of the effects of regulatory peptides on cell proliferation and DNA synthesis.

B-Lymphocytes↗
PubMed1991

Human T-lymphocytes synthesize and secrete a protease resistant proteoglycan in a delayed, serum-dependent response to concanavalin A.

In the presence of radioactive precursors, the addition of Concanavalin A (Con A) to cultures of mononuclear cells (MC) from human blood resulted in marked accumulation in the medium of a protease-resistant proteoglycan (PG) with chondroitin sulfate (CS) chains of an average molecular weight of 28 KDa. This PG was shown to be elaborated primarily by T-cells. The addition of serum was necessary for maximal stimulation with Con A and under these conditions PG accumulation in the medium rose slowly during the first few days of culture and much more rapidly between days 6-8.

Blood↗
PubMed1991

Liposomal amphotericin B (AmBisome) in the treatment of fungal infections in neutropenic patients.

The use of high-dose chemotherapy and the subsequent prolonged neutropenia in patients with haematological diseases has resulted in an increased incidence of fungal infections. The diagnosis and treatment of these infections in neutropenic patients pose major therapeutic problems. The only drug with proven efficacy in the treatment of deep-seated fungal infections, including invasive aspergillosis, is amphotericin B. Unfortunately, this drug has adverse side effects, most importantly dose-dependent nephrotoxicity; furthermore, some patients fail to show a response to amphotericin B. We have treated 20 patients undergoing myeloablative chemotherapy and/or bone marrow transplantation for haematological diseases with liposomal amphotericin (AmBisome) for proven or suspected aspergillosis. Eighteen patients had diffuse interstitial pneumonitis and two patients had suspected fungal liver abscesses. Five patients had mycologically proven fungal infection and of these, three patients (60%) showed a complete response to liposomal amphotericin. Eleven patients received liposomal amphotericin because of the failure of conventional amphotericin B to eradicate proven or suspected fungal infection. Five of these 11 patients (45%) showed a complete clinical response to liposomal amphotericin. Eight patients received liposomal amphotericin because of pre-existing renal impairment or nephrotoxicity caused by conventional amphotericin B. Four of these patients (50%) showed a response to liposomal amphotericin. Recovery from probable fungal infection in this group of patients occurred when there was complete remission of underlying disease and recovery of neutrophil counts, when they were concurrently treated with liposomal amphotericin.

Adolescent↗
PubMed1991

Successful treatment of acute myeloid leukemia beyond first remission with autologous bone marrow transplantation using busulfan/cyclophosphamide and unpurged marrow: the British autograft group experience.

The results in 34 adult patients with acute myeloid leukemia (AML) who have undergone autologous bone marrow transplantation (ABMT) using busulfan and cyclophosphamide (Bu/Cy) in 12 United Kingdom (UK) centers have been analyzed. There were 19 females and 15 males; median age was 40 years (range, 21 to 62 years). Nine patients were in first relapse; 25 were in second remission. The median time of first remission for the whole group was 11.5 months (range, 1 to 56 months). All the patients in first relapse and six patients in second remission received first remission marrow. The leukemia-free survival (LFS) for the patients in first relapse was 33%, with a median follow-up of 20 months. The LFS for the patients in second remission was 48% with a median follow-up of 26 months. The length of second remission exceeds the length of first remission in 14 patients. Considerable toxicity with hemorrhagic cystitis (four patients; none fatal), venoocclusive disease (four patients; one fatal), pneumonitis (four patients; one fatal), intracranial hemorrhage (two patients; two fatal) has occurred. There have been four procedure-related deaths (12%). Hematologic recovery was satisfactory for neutrophils (median time to 0.5 x 10(9)/L, 22 days [range, 11 to 101 days]), but very slow for platelets (median time to 50 x 10(9)/L, 62 days [range, 15 to 1,080 days]). This study suggests that the use of Bu/Cy with ABMT for patients beyond first remission in AML compares favorably with chemotherapy, and although the procedure-related mortality is acceptable, it is associated with protracted platelet recovery.

Acute Disease↗