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Biomedical subjects

R E Marcus

Publications and source records attributed to R E Marcus.

At least 37 records · Page 2Linked to original sources
PubMed1996

Severe hemosiderosis post allogenic bone marrow transplantation.

Abnormal liver function persisting late after allogeneic BMT is usually attributed to chronic GvHD, viral hepatitis or drug toxicity. We describe a patient who had negative hepatitis serology, was on no hepatotoxic medication, had no evidence of GvHD but had abnormal liver function 15 months post MBT. She was diagnosed as having grade IV hemosiderosis of the liver. Her total red cell support had only been 52 units. We therefore postulate that in a proportion of patients receiving allogeneic BMT impaired intestinal iron absorption may be an important cause of hemosiderosis.

Bone Marrow Transplantation↗
PubMed1996

Interstitial pneumonitis as a late complication of high dose therapy with cyclophosphamide/thiotepa and peripheral blood progenitor cell rescue for carcinoma of the breast.

The incurability of metastatic breast cancer with conventional chemotherapy has prompted many units to investigate the role of high dose chemotherapy and autologous stem cell rescue in patients with advanced or poor risk primary disease. Although preliminary data from centres treating patients with these modalities are encouraging, both in terms of rapidity of haemopoietic recovery and progression free survival, there is nonetheless a procedure related toxicity. We describe a patient with inflammatory carcinoma of the breast who received high dose cyclophosphamide and thiotepa prior to peripheral blood progenitor cell rescue, and developed a steroid responsive interstitial pneumonitis 10 weeks after stem cell infusion.

Adenocarcinoma↗
PubMed1996

t(9;13)(q34;q12) chromosomal translocation persisting 4 years post autologous bone marrow transplantation for secondary AML despite morphological remission.

A 42-year-old male patient with a history of occupational exposure to benzene presented with pancytopenia. His bone marrow showed evidence of trilineage dysplasia and cytogenetic analysis revealed a unique t(9;13)(q34;q12) translocation. Five months after diagnosis he developed secondary AML. He was treated with four courses of chemotherapy and an autologous bone marrow transplantation (BMT). Four years post-transplantation he remains in haematological and morphological remission though the cytogenetic abnormality is still present in all metaphases examined.

Acute Disease↗
PubMed1996

Hodgkin's disease after cardiac transplant: a report of two cases.

Non-Hodgkin's lymphoma is a well recognized sequela of transplant related immunosuppression. Hodgkin's disease has only rarely been described in this context. We describe two cases of Hodgkin's disease after heart and heart/lung transplants respectively. Both patients continued to receive immunosuppressive therapy with cyclosporin and prednisolone, and received combination chemotherapy. One died of Aspergillus infection following the second course of chemotherapy. The other patient completed his chemotherapy and remains in remission. We discuss the possible aetiology and management of post-transplant Hodgkin's disease.

Adult↗
PubMed1996

Bacterial contamination of peripheral blood progenitor cells for transplantation.

Peripheral blood progenitor cells (PBPC) were obtained from 128 apheresis harvests on 64 patients and were tested in duplicate for microbiological contamination (1) after collection and (2) after thawing, following processing and cryopreservation. In this study we have attempted to improve the monitoring of contamination in peripheral blood progenitor cell collections by identifying exogenous contamination that probably originated from the testing laboratory and is therefore not clinically significant. We found no contamination in 82% of harvests, 1.6% of harvests to be significantly contaminated and organisms were isolated from 16.4% that were assessed as clinically nonsignificant. Our experience indicates that the choice of microbiological methods will influence the results and their clinical relevance. No samples were positive by direct culture. We recommend that sampling should be performed at more than one stage during the procedure and that initially only the post-thaw samples be analysed. Testing should be performed by enrichment culture in duplicate only and if positive to aid interpretation the post-collection sample should then be cultured. No patient given nonsignificantly contaminated graft without antibiotic cover suffered infection from the identified organism. The incidence of significant contamination was low and we recommend that in these cases PBPC grafts can be infused safely provided prophylactic antibiotic cover is given.

Bacteriological Techniques↗
PubMed1996

Posterior hip dislocations: a cadaveric angiographic study.

Avascular necrosis (AVN) of the femoral head after a traumatic posterior hip dislocation (Thompson and Epstein type I) has been hypothesized to occur due to changes in blood flow. However, to the best of our knowledge of the English literature, a human cadaveric angiographic study has never been performed to delineate these vascular changes. Six fresh frozen human cadavers were used to examine the effects of posterior hip dislocation on the extraosseous and intraosseous blood supply to the femoral head and neck. After a forceful posterior hip dislocation was performed on the cadavers, the proximal vessels were injected with a radioopaque colored latex liquid polymer (Microfil) and examined under cinefluoroscopy. The contra lateral hips were used as controls and were examined in a similar manner. Both hips of the cadavers were harvested, and a macroscopic and microscopic examination was performed. The cine-fluoroscopic examination delineated the dynamic effects of posterior dislocation on the surrounding vasculature. Filling defects were most notable at the junction of the external iliac and common femoral arteries. Filling defects were also present in the circumflex vessels. Compared to controls, the common femoral and circumflex vessel filling defects were statistically significant (p < 0.004). These defects were secondary to an apparent stretching and twisting of the artery caused by the pull and rotation of the dislocated hip. A number of collateral vessels from the gluteal arteries were also demonstrated on fluoroscopic examination. The macro and microscopic examination did not show a qualitative or a quantitative difference in the amount of latex present in the dislocated and control groups. Based on the results of this study, changes in the extraosseous blood flow to the dislocated hip do occur. The vessels that appear to be most affected by the dislocation are the common femoral and circumflex vessels. However, these extraosseous changes do not consistently result in changes in the intraosseous blood flow possibly due to collateral circulation. Relocating the femoral head in a traumatic posterior hip dislocation may provide earlier blood flow to the femoral head by relieving tension across the femoral and circumflex vessels. Delayed relocation could contribute to the development of AVN in the femoral head by not only inducing immediate ischemia at the time of injury but by also producing a progressive and delayed form of arterial damage in the femoral and circumflex vessels. AVN may not be an absolute outcome of posterior hip dislocations due to preexisting collateral circulation and/or the preservation of the femoral circumflex vessels.

Aged↗
PubMed1996

Short-course intravenous antibiotics with oral quinolone prophylaxis in the treatment of neutropenic fever in autologous bone marrow or peripheral blood progenitor cell transplant recipients.

The effectiveness of short-course intravenous antibiotics concurrent with prophylactic oral ciprofloxacin in the treatment of neutropenic fever was studied in 81 patients undergoing autologous bone marrow or peripheral blood progenitor cell transplantation (ABMT or PBPCT). During the neutropenic period following ABMT or PBPCT, 10/81 (12%) patients did not require treatment with intravenous antibiotics. Seventy-one patients required antibiotics. Forty-seven of the 71 (66%) responded to 72 h treatment with gentamicin, azlocillin or ceftazidime, and vancomycin. Thirty-three of the 47 (70%) responders had a complete resolution of their fever with no further recurrence. Fourteen of the 47 responders developed a second fever between 2 and 25 days after stopping first-line antibiotics. Eleven of the 14 patients responded to a second course of intravenous antibiotics. Twenty-four of the 71 patients did not respond to intravenous antibiotics and were treated with intravenous amphotericin and the intravenous antibacterial agents were discontinued. Eighteen of the 24 patients responded to amphotericin. The 6 patients who had persistent fever resolved their temperature when their neutrophil count recovered. There were no deaths due to infection during the study. Short-duration intravenous antibiotics in conjuction with oral ciprofloxacin prophylaxis are a safe and effective treatment for neutropenic fever.

Adolescent↗
PubMed1996

The role of internal fixation in the treatment of Jones fractures in diabetics.

The purpose of this study was to evaluate the treatment of fractures of the proximal fifth metatarsal at the junction of the metaphysis and diaphysis (i.e., Jones fracture) in diabetics. Open reduction and internal fixation with bone grafting resulted in clinical and radiographic union 8 weeks after surgery in patients treated with either immediate or delayed open reduction and internal fixation. Open reduction and internal fixation with autologous bone grafting is an effective treatment regimen in the diabetic patient with a Jones fracture. An initial trial of casting can be attempted without any apparent deleterious effects on secondary open reduction and internal fixation.

Adult↗
PubMed1996

High-dose carmustine, etoposide and melphalan ('BEM') with autologous stem cell transplantation: a dose-toxicity study.

We have investigated the toxicity of dose-escalation of BCNU, etoposide and melphalan ('BEM') chemotherapy with autologous stem cell transplantation in patients with haematological malignancies. Seventy-two patients with haematological malignancies were treated with BCNU (600 mg/m2, 450 mg/m2 or 300 mg/m2), etoposide 2 g/m2 and melphalan 140 mg/m2 followed by autologous bone marrow transplantation (ABMT), n = 51, or autologous peripheral blood progenitor cell transplantation (APBPCT), n = 21. Liver and pulmonary function was monitored pretransplant and at regular intervals post-transplant. Mucositis was graded daily during in-patient stay. There was a significantly higher incidence of symptomatic pulmonary toxicity in the patients who received BCNU at 600 mg/m2 than in the other two groups, and there was a significant increase in the incidence of asymptomatic decrease in carbon monoxide (KCO) in the patients who received BCNU 450 mg/m2. There was no significant difference between the three groups in the incidence and severity of mucositis or in the incidence of transiently abnormal liver function. We conclude that etoposide at 2 g/m2 can be used without unacceptable mucositis. BCNU at 600 mg/m2 is associated with an unacceptably high incidence of lung toxicity, but at 450 mg/m2 there is minimal symptomatic lung toxicity.

Adolescent↗
PubMed1996

Peripheral blood progenitor cell transplantation: a single centre experience comparing two mobilisation regimens in 67 patients.

Between June 1991 and January 1995 we performed 67 peripheral blood progenitor cell transplants (PBPCT). Ten patients (group 1) were mobilised with 7 gm/m2 of cyclophosphamide followed by daily G-CSF injections (5 micrograms/kg, subcutaneously). When the white cell count reached 1 x 10(9)/1 they were leukapheresed for 5 days. After stem cell infusion they received G-CSF (10 micrograms/kg/day) until the neutrophil count reached 1.5 x 10(9)/1. Fifty-six patients had PBPCs mobilised with 3 gm/m2 of cyclophosphamide followed by daily subcutaneous G-CSF (5 micrograms/kg) and PBPCs were harvested on 2 consecutive days, when the white cell count rose to 4 x 10(9)/1. After stem cell infusion this group did not receive G-CSF. In 47 of the 56 patients (group 2) adequate MNC (> or = 4 x 10(8)/kg) and/or CFU-GM (> or = 10 x 10(4)/kg) were obtained. Insufficient MNC and/or CFU-GM were obtained in 10 patients. They were therefore transplanted using a combination of bone marrow and peripheral blood progenitor cells (group 3). Overall 64 patients successfully engrafted. Median days to neutrophils > or = 0.5 x 10(9)/1 were 9 (range 8-13), 12 (range 8-25) and 11 (range 9-16) and to platelets > or = 50 x 10(9)/1 were 11 (range 9-23), 13 (range 9-90) and 16 (range 13-99) in groups 1, 2 and 3 respectively. Patients in group 1 had a faster neutrophil recovery than patients in group 2 (P = 0.0002). The three patients who failed to engraft all received a combination of autologous peripheral blood and bone marrow cells.

Adolescent↗
PubMed1996

High-dose therapy and autologous stem cell rescue for poor risk and refractory lymphoma: a single centre experience of 123 patients.

Over an 8-year period we autografted 123 patient with poor-risk lymphoma. Sixty-three patients had Hodgkin's disease (HD) and 60 non-Hodgkin's lymphoma (NHL). Of the patients with HD, 45 had responsive and 18 resistant disease prior to high-dose therapy. Fifty-three patients with NHL had responsive and seven had resistant disease at the time of transplantation. Seventy-seven patients received autologous bone marrow (BM) rescue, 39 autologous peripheral blood progenitor cell (PBPC) rescue, and seven combined BM and PBPC rescue. High-dose chemotherapy was BEM in 67, BEAM in 39, TBI and cyclophosphamide or etoposide or BCNU in 10, etoposide/mitozantrone in six and etoposide/melphalan in one. There was eight (6.5%) deaths due to treatment-related toxicity, within the first 100 days post-transplantation. Of the patients with HD 41 (65%) are alive at a median follow-up of 39 months (range 2-94). Thirty-three (52%) patients remain in CR. The median DFS of the 63 patients with HD is 34 months (95% CI 7-61). The median DFS for patients transplanted with responsive disease was significantly better than for those transplanted with refractory disease (61 vs 21 months P < 0001). Thirty-five (58%) of the patients with NHL are alive, and 20 (33%) remain in CR. The median DFS for patients transplanted with responsive and refractory disease was 11 months (95% CI 3-19) and 4 months (95% CI 0-9; P = NS) respectively. The median DFS for patients transplanted with HD was significantly better than for patients transplanted with NHL (34 vs 8 months, P < 0.002). In both groups there was no significant difference in DFS in patients receiving one, two, three or more lines of therapy prior to transplantation. In summary, in patients with poor-risk lymphoma who have responsive disease high-dose therapy may result in durable CRs. Conversely, only a small proportion of patients with HD or NHL with resistant disease achieve CR after autologous stem cell rescue.

Adolescent↗
PubMed1996

Measurement of reticulated platelets following peripheral blood progenitor cell and bone marrow transplantation: implications for marrow reconstitution and the use of thrombopoietin.

Neutrophil and platelet engraftment times are significantly shorter in patients undergoing PBPCT compared with ABMT. The explanation for this is unclear. The reticulated platelet percentage (RP%) has been established as a measure of bone marrow platelet production. Using this measurement we have followed thrombopoiesis over the transplant period in 10 patients undergoing PBPCT, eight ABMT and four alloBMT. Neutrophil and platelet engraftment times were significantly shorter in patients undergoing PBPCT than either ABMT or alloBMT. The RP% fell to a nadir in parallel with the platelet count in all patients following conditioning therapy consistent with an aplastic state and rose before platelet recovery as young platelets were released. The peak rise in the RP% was significantly greater and occurred earlier in PBPCT compared with BMT. The total number of reticulated platelets released during the time of engraftment was significantly greater in PBPCT than BMT. The potential role of the RP% in the timing of thrombopoietin therapy is explored. Finally the diagnostic use of the RP% in post-transplant thrombocytopenia is illustrated by a case in which a persistently high RP% accurately predicted a consumptive aetiology.

Adolescent↗
PubMed1996

Improved yield of peripheral blood progenitor cells on the Cobe Spectra.

The efficiency of leucapheresis using the Cobe Spectra depends on the observation of the operator to monitor the haematocrit (Hct) in the collection line at the recommended Hct of 1%. Cells were harvested by processing 3 x total blood volume (TBV) over 3-4 h. During the harvest the manual Hct and the colony-forming units granulocyte-macrophage (CFU-GM) concentrations were analysed in the collection line in the observed Hct range of 1-7.5%. There was a correlation between the manual and observed Hct (r = 0.97). The CFU-GM concentration was normalised to allow comparison between patients. The increase was statistically significant between 1-2% (P = 0.04) and 1-3% Hct (P = 0.05). The increase in CFU-GM concentration remained at the termination of harvest, indicating that not all available CFU-GM were harvested. The optimum concentration of progenitor cells was found to be at 3% Hct. We postulate that this may permit the collection of sufficient cells on one occasion to allow PBPC autografting in the majority of patients who respond to mobilisation.

Adult↗
PubMed1995

Plastic-adherent progenitor cells in mobilized peripheral blood progenitor cell collections.

The use of peripheral blood progenitor cells (PBPC) to reconstitute hematopoiesis after high-dose chemoradiotherapy is now commonplace in the treatment of malignancies. Attempts to characterize these cells have concentrated primarily on their phenotype and their content of clonogenic colony-forming cells (CFC). We have used a plastic-adherent delta (P delta) assay system to evaluate the quantity and quality of more primitive cells in addition to the conventional measurements of CFC and CD34-positive cells. The leukapheresis products from 20 patients mobilized using cyclophosphamide (Cy) and granulocyte colony-stimulating factor (G-CSF) were examined for progenitor cell content. The mean number of mononuclear cells (MNC), colony-forming units-granulocyte/macrophage (CFU-GM), and CD34-positive cells from two leukaphereses per patients were 7.9 x 10(8)/kg, 47.3 x 10(4)/kg, and 10.5 x 10(6)/kg, respectively. The mean number of P delta progenitors was 9.3 x 10(4)/kg. Limiting dilution analyses showed the frequency of P delta progenitors in PBPC to be between 1 and 5.3 per 10(5) MNC and that each P delta progenitor has the proliferative capability to generate an overall mean of 4.5 CFU-GM. Of the 20 patients, 16 underwent autografting with PBPC alone. Fifteen patients engrafted neutrophils and platelets within 16 days. One patient had delayed engraftment associated with inadequate etoposide clearance. Statistical analysis showed a strong correlation between numbers of CFU-GM and CD34 positivity. The numbers of plastic-adherent P delta progenitor cells did not correlate with CFU-GM or CD34-positive cells. We conclude that the plastic-adherent P delta progenitor cell assay is capable of measuring primitive hematopoietic cells and that it may be useful for the investigation of primitive progenitors in PBPC harvests.

Antigens, CD34↗