PubMed Health⌕ Search

Biomedical subjects

J M Rowe

Publications and source records attributed to J M Rowe.

At least 109 records · Page 6Linked to original sources
PubMed1994

Clinical use of hematopoietic growth factors in allogeneic bone marrow transplantation.

The use of the recombinant hematopoietic growth factors G-CSF and GM-CSF have shortened the period of neutropenia, or avoided this problem, in many cancer patients who have received cytotoxic therapy. Although these benefits have been particularly striking in the autologous bone marrow and/or autologous peripheral blood progenitor cell transplant setting, most data suggest that the use of G-CSF and GM-CSF only marginally enhance recovery of the neutrophil count when administered after allogeneic bone marrow infusion. Furthermore, in the allograft setting these expensive agents have not provided benefit in the form of enhanced platelet count recovery, lessening the incidence of graft-versus-host disease, or improvement in overall survival. These data do not justify routine widespread use of G-CSF and GM-CSF and suggest that these agents should be reserved for patients who experience delay in engraftment after allogeneic bone marrow infusion. Administration of erythropoietin, on the other hand, may reduce the need for homologous red blood cell transfusions, and may increase the safety margin for both the allogeneic bone marrow recipient and as well as the donor. Recombinant hematopoietic growth factors targetted specifically to enhance platelet recovery after transplantation (such as interleukin-3, interleukin-6, and interleukin-11) have shown promise after autotransplantation and after conventional dose chemotherapy, and likely will be evaluated in the allogeneic transplant patient.

Bone Marrow Transplantation↗
PubMed1994

Leukocyte-reduced transfusions of ABO-identical platelets and clinical outcome in autologous bone marrow transplantation for lymphoma.

In observational studies, use of ABO-identical platelets and leukocyte-reduced blood components have been associated with prolonged survival and reduced morbidity in acute leukemia. We present an analysis of the clinical results of instituting a policy of ABO-identical, leukoreduced transfusions in adult patients with lymphoma undergoing autologous bone marrow transplantation. Consecutive patients with Hodgkin's disease or non-Hodgkin's lymphoma were treated with a BEAC conditioning regimen. The use of ABO-identical platelets and leukoreduction of blood components was associated with reductions in mean number of days with fever > or = 38.5 degrees C (17 vs 10), number of days of antibiotics (34 vs 22) and numbers of days until recovery of neutrophil count > or = 500 x 10(6)/l (26 vs 18). Use of leukoreduced transfusions was the only statistically significant treatment factor predicting more rapid neutrophil engraftment. No significant difference in event-free or overall survival was observed. The differences in morbidity were not explained by variations in supportive care such as use of hematopoietic growth factors, use of peripheral blood stem cells or by any measures of pretransplant disease extent or severity. While conclusions based on cohort studies must be viewed conservatively, these data are consonant with observations from previous animal models and clinical studies. ABO-identical platelet transfusions and leuko-reduction are associated with reduced morbidity in patients undergoing autologous bone marrow transplantation for lymphoma.

ABO Blood-Group System↗
PubMed1993

ABO and platelet transfusion revisited.

Historically, ABO compatibility between donor and recipient has been considered of minor importance for platelet transfusion. However, in a recent randomized trial we showed that provision of only ABO-identical platelets was associated with a significantly higher corrected count increment (CCI) in the early transfusions and with a twofold reduction in refractoriness, as compared with platelets given unmatched for ABO. In older studies this phenomenon was not observed. We wondered whether in these previous studies the use of the conventional term "ABO compatible", whereby ABO-identical platelet transfusions are grouped with those that are merely ABO compatible, might have obscured the advantages of the ABO-identical platelets. In this paper the CCI from our original study are compared with what would have been found had the conventional terminology of "ABO compatible" and "ABO incompatible" been used. In our original study the mean CCI in patients receiving only ABO-identical platelets was 64% higher than that achieved with ABO-unmatched products. However, when the transfusions were reanalyzed according to conventional terminology of ABO "compatible" and "incompatible," the actual benefits of ABO-identical platelets were no longer detected. Thus, had we used the conventional terminology in the original study we would have come to completely different conclusions about the importance of ABO in platelet transfusion. We hypothesize that transfusion of ABO-incompatible plasma leads to the formation of immune complexes that can destroy compatible platelets by indirect mechanisms. This model predicts that the success of a transfusion could be affected by previous incompatible transfusions. When transfusions were classified as to whether they were first, second, or third unmatched transfusion, increasing numbers of transfusions of ABO-incompatible plasma were associated with progressively poorer mean increments. The same was true for platelet ABO-incompatible transfusions. In contrast, increasing numbers of ABO-identical transfusions were not associated with poorer increments. The failure to appreciate that (a) transfusions containing ABO-incompatible plasma yield poor increments and (b) the effects of ABO-nonidentical transfusions are cumulative, and therefore affect the success of subsequent identical transfusions, may have led in the past to the incorrect conclusion that ABO matching was of minor importance in repetitively transfused patients.

ABO Blood-Group System↗
PubMed1993

The changing course of thrombotic thrombocytopenic purpura and modern therapy.

Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder of unknown etiology. Pathologically, there appears to be an abnormal interaction between the vascular endothelium and platelets, but the primary event remains uncertain. While historically, TTP was a fatal disease, dramatic improvement in its outcome has occurred over the past two decades with the development of effective therapy. Plasma infusion or exchange remains the cornerstone of the treatment of TTP, along with corticosteroids, platelet inhibitor drugs, vincristine and splenectomy. This review summarizes the clinical findings, what is known of the pathogenesis and the available therapeutic modalities for TTP. In most cases, remissions can be attained and cures are now common. However, approximately half the patients will relapse. The clinical course at relapse is usually milder than the disease at presentation and less aggressive therapy may be needed. However, relapsing TTP still carries a significant mortality and preventive therapies are not always effective. Further progress may have to await an understanding of the fundamental etiology of this disease.

Adult↗
PubMed1993

Does in vitro bone marrow purging improve the outcome after autologous bone marrow transplantation?

High-dose therapy with bone marrow rescue is now regarded as an effective treatment for a variety of malignancies. In an attempt to circumvent the scarcity of HLA-matched donors, autologous marrow has been successfully used as the source of cells for hematopoietic reconstitution. There has been considerable controversy as to whether any malignant cells present in the graft could contribute to relapse of disease post-transplant. In this paper we review clinical results obtained by using autologous transplantation and present evidence on how ex vivo tumor purging may contribute to the outcome.

Acute Disease↗
PubMed1993

Circulating immune complexes involving the ABO system after platelet transfusion.

It has been proposed that when ABO unmatched platelets are transfused circulating immune complexes (CIC) may be formed between the patient's soluble ABH antigens and the transfused antibodies. Platelets might then be destroyed by bystander mechanisms or by the binding of CIC to the Fc receptor or to C3 binding membrane proteins on the platelet. An ELISA C1q assay was used to detect CIC in 40 patients with haematological diseases who had received multiple platelet transfusions. A significantly larger number of refractory patients were positive (41%) in the assay than non-refractory patients (13%) or normal blood donors (0%). The presence of circulating IgG anti-A was sought in six group A refractory patients who had been transfused with ABO unmatched platelets. To determine whether the IgG anti-A was monomeric or in high molecular weight complexes, the serum was fractionated by gel exclusion chromatography and fractions were tested for the presence of IgG anti-A. In all six patients the peak of IgG anti-A binding occurred in fractions of high molecular weight (200-900 kD). Five out of six patients also demonstrated anti-A activity in fractions corresponding to monomeric IgG (about 150-180 kD). Fractions containing high molecular weight anti-A were purified using a protein G column and the eluates were tested for the presence of group A antigen using dot immunoblotting. Group A antigen was associated with the purified IgG anti-A in 4/5 patients tested. Appropriate transfused and non-transfused controls had no anti-A in any fractions. Although not unexpected, these studies demonstrate for the first time that refractory patients receiving ABO unmatched platelets have CIC composed of ABO antigens and their corresponding antibodies present in their serum that circulate for at least several days. It also confirms the hypothesis that some CIC in haematological patients are induced by transfusion.

ABO Blood-Group System↗
PubMed1993

The role of ABO matching in platelet transfusion.

A prospective controlled trial was performed to determine whether the use of ABO-identical platelets from the start of treatment might provide higher post-transfusion platelet increments, reduce the number of platelet transfusions and ultimately delay the onset of refractoriness. Forty newly diagnosed patients with haematological diseases were randomized to receive either pooled ABO-identical platelets or pooled platelets unmatched for ABO group throughout their course. The corrected platelet count increments (CCI) were calculated for the first 25 transfusions of each patient and non-immune factors present at the time of each platelet transfusion were documented. The mean CCI for the first 25 transfusions in the ABO-identical group was significantly higher (6600 +/- 7900 SD) than that achieved with ABO unmatched platelets (5200 +/- 7900; p < 0.01). The effect was most marked for the first 10 transfusions for each patient where the CCI was 64% higher in the ABO-identical group (8200 +/- 7500 vs 5000 +/- 8100; p < 0.0002). Patients given ABO-identical platelets required only about half as many transfusions in the first 30 days (10 versus 17, p < 0.05) or during the first admission (11 versus 21 p < 0.01) as patients in the ABO-unmatched group. A smaller percentage of patients in the ABO-identical group became refractory (36% vs 75% p < 0.03). The data suggest that patients requiring long-term platelet support should be transfused with ABO-identical platelets.

ABO Blood-Group System↗
PubMed1993

One hundred autotransplants for relapsed or refractory Hodgkin's disease and lymphoma: value of pretransplant disease status for predicting outcome.

PURPOSE: One hundred autotransplants for Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) were examined prospectively to identify variables with prognostic significance. PATIENTS AND METHODS: Ninety-six patients with relapsed or refractory HD or NHL underwent 100 autotransplants. Patients received high-dose carmustine (BCNU), etoposide, cytarabine, and cyclophosphamide (BEAC) followed by unpurged autologous stem-cell rescue. RESULTS: The 3-year actuarial event-free survival (EFS) rate for the 47 HD patients is 49%, with a median followup duration of 2 years. For the 53 NHL patients, the 3-year actuarial EFS rate is 40%, with a median follow-up duration of 19 months. By multivariate analysis, minimal disease on admission (all areas < or = 2 cm) is associated with improved EFS (HD, P = .003, NHL, P = .03). The projected EFS rate for HD patients entering with minimal disease is 70% versus 15% for patients with bulky disease (P = .0001). The projected EFS rate for NHL patients with minimal disease is 48% versus 25% for patients with bulky disease (P = .04). Posttransplant involved-field radiotherapy, administered to 26 of the last 61 patients, was associated with an improved EFS rate for NHL patients (P = .015). The BEAC regimen was well tolerated by patients who entered the study with minimal disease (mortality rate, < 5%), but caused significant toxicity in patients with bulky disease (mortality rate, 25%). CONCLUSION: Disease burden before autotransplantation is an important predictor of regimen-related toxicity and EFS. Posttransplant involved-field radiotherapy may improve outcomes in select patients with NHL. The BEAC regimen is safe and effective, particularly for patients with minimal disease.

Actuarial Analysis↗
PubMed1993

Treatment of minimal residual disease in myeloid leukemia--the immunotherapeutic options with emphasis on Linomide.

It is now known that syngeneic transplantation, T lymphocyte depletion and absence of graft-versus-host disease all increase the risk of relapse following allogeneic transplantation for the myeloid leukemias, both acute and chronic. Leukemia-specific immune responses appear to play a major role in the therapy of the myeloid leukemias. In recent years attempts have been made to better characterize and effectively utilize these antileukemic immune responses, concentrating on clinical states of minimal residual disease. This review will discuss the role of such immunotherapy following autologous bone marrow transplantation for myeloid leukemias, and will focus on recent experience and ongoing clinical trials using the novel immunomodulator Linomide.

Adjuvants, Immunologic↗
PubMed1992

Treatment of relapsed or refractory Hodgkin disease and non-Hodgkin lymphoma with high-dose chemoradiotherapy followed by unstimulated autologous peripheral stem cell rescue.

Nine patients with relapsed or refractory Hodgkin disease or non-Hodgkin lymphoma underwent peripheral stem cell autografting because of a history of marrow involvement with visible lymphoma. Peripheral stem cells were collected during a process of unstimulated leukapheresis. Recovery to a neutrophil count of 0.1 x 10(9)/L was seen at a median of 14 days compared with a median of 18 days for a concurrent series of marrow recipients (P = .12). Recoveries to a neutrophil count of 0.5 x 10(9)/L and a platelet count of 50 x 10(9)/L occurred at medians of 25 days and 28 days, respectively. These figures are not significantly different from those obtained in the marrow recipients. Of the original nine patients, six are surviving free of disease progression or relapse at a median of 240 days posttransplant. Two patients died of transplant-related complications and one relapsed 250 days post-transplant. All surviving patients remain independent of transfusions and six have attained almost complete hematological reconstitution. Although administration of cytotoxic therapy and granulocyte-macrophage colony-stimulating factor (GM-CSF) may enhance the yield of early progenitor cells during leukapheresis, unstimulated leukapheresis results in a stem cell product capable of rapidly restoring and sustaining marrow function even after multiple courses of intensive "salvage" therapy. Additional follow-up will be needed to determine whether preliminary survival figures continue to compare favorably with those of patients with similar extramedullary disease states undergoing marrow transplants.

Adult↗
PubMed1992

Antibodies to plasma proteins: an association with platelet transfusion refractoriness.

We hypothesized that antibodies to HLA-linked polymorphic plasma proteins could be involved in platelet refractoriness by an 'innocent bystander' or immune complex mechanism. Employing a kinetic enzyme-linked immunosorbent assay (ELISA) technique the ability of IgG from the plasma of refractory patients to bind to albumin, fibrinogen, complement components C2 and C4 was measured. As compared with controls a high percentage of refractory patients had increased IgG capable of binding to all four plasma proteins: C2 (83%), C4 (83%), albumin (75%), fibrinogen (34%). In the presence of exogenous plasma proteins these antibodies mediated increased deposition of IgG onto normal donor platelets. The plasma protein binding IgG consisted both of monomeric IgG and a broad range of high molecular weight complexes. IgG anti-plasma protein antibody could be eluted from platelets of refractory patients. The development of anti-plasma protein IgG was studied during the course of platelet transfusion therapy and found to increase progressively so that by the 20th transfusion greater than 90% of samples were positive. The presence of plasma protein binding activity correlated with the development of increased levels of platelet bound IgG and refractoriness. Multiple platelet transfusions lead to sensitization to polymorphic determinants on C2 and C4 as well as the formation of high molecular weight complexes. These antibodies and complexes contribute to the deposition of IgG on platelets and may contribute to refractoriness.

Albumins↗
PubMed1992

Hemopoietic growth factors: a review.

The hemopoietic growth factors are peptide hormones that are known to be responsible for the in vitro and in vivo proliferation of bone marrow progenitor cells into mature differentiated cells. These cytokines have had a major impact on the management of patients with cytopenias and have been extensively used as an adjunct to the management of patients with hematologic malignancies, with or without prior intensive chemotherapy. Other potential uses, being rigorously studied, include the potential mobilization of stem cells as well as recruitment phase-specific cells into the cell cycle, thus providing a more sensitive environment for targeting specific chemotherapeutic agents.

Acute Disease↗
PubMed1992

Response to plasma exchange and splenectomy in thrombotic thrombocytopenic purpura. A 10-year experience at a single institution.

BACKGROUND: This study was designed to assess the response of patients with thrombotic thrombocytopenic purpura to plasma exchange and to evaluate the role of splenectomy after relapse. METHODS: The records of all patients with thrombotic thrombocytopenic purpura who had plasma exchange as primary treatment at a single center during a 10-year period were retrospectively reviewed. Response to the initial course of plasma exchange was determined, and the clinical outcome was evaluated in patients whose conditions were either refractory to exchange, responded without relapse, or relapsed after initial response. The outcome of patients treated during relapse with splenectomy was evaluated. A literature review was conducted to determine the clinical outcome in patients treated similarly. RESULTS: Twenty-seven patients for whom data could be evaluated had been treated in the 10-year period. Twenty-one (78%) responded to the plasma exchange, but the conditions of six (22%) were refractory and these patients died. Eight patients (30%) had one or multiple relapses after initial response but had prolonged remissions after additional plasma exchange alone (two patients) or splenectomy (six patients). A review of 19 reports, including 224 patients with thrombotic thrombocytopenic purpura initially treated with plasma exchange, revealed similar findings, with initial response in 81%, refractoriness in 19%, and relapse after initial response in 27% of patients. CONCLUSION: Response to plasma exchange in thrombotic thrombocytopenic purpura is associated with an excellent prognosis, and most deaths occur in patients whose conditions are refractory. Relapses after initial response are frequent but can be managed successfully with additional plasma exchange or with splenectomy, which often induces long-term remissions.

Adult↗
PubMed1991

Regulation of IL-6 expression by oncostatin M.

Endothelial cells produce immunomodulatory cytokines in response to soluble mediators of inflammatory/immune reactions. We have previously demonstrated that the leukocyte-derived cytokine, oncostatin M (Onco M) can alter endothelial cell morphology, regeneration, and fibrinolytic activity in vitro. Here we demonstrate that Onco M stimulates the production of the pleiotropic cytokine, IL-6, in cultured human endothelial cells (HEC) in a time- and dose-dependent manner. Specific antibodies to IL-6 neutralize the growth-inhibitory activity for human breast carcinoma cells that is secreted by HEC in response to Onco M treatment. Specific immunoassays indicate greater than 10-fold increases in the IL-6 content of culture supernatants as early as 6 h post-treatment with Onco M (ED50 = 17 pM). This stimulation of IL-6 production by Onco M is associated with a sevenfold increase in intracellular levels of IL-6 mRNA. IL-1 alpha and TNF-alpha are also potent inducers of IL-6 production in these cells, the order of potency being IL-1 alpha greater than Onco M greater than TNF-alpha. TNF-alpha, but not IL-1 alpha, synergizes with Onco M to augment IL-6 production in HEC. HEC are 10 to 20 times more responsive to Onco M than are other nonendothelial cell types. In addition, HEC express 10 to 20 times greater numbers of high affinity cell-surface receptors for Onco M than do other nonendothelial cell types. Based on these findings, we propose that Onco M may represent a new immunomodulator regulating cytokine-induced gene products in endothelial cells.

Antineoplastic Agents↗