Biomedical subjects

David J Inwards

Publications and source records attributed to David J Inwards.

23 records · Page 2Linked to original sources

PubMed2003

Acute neuropathies after peripheral blood stem cell and bone marrow transplantation.

Neuromuscular complications are not uncommon after bone marrow and stem cell transplantation, especially in patients with allogeneic transplantations and graft-versus-host disease. The pathogenesis of these complications remains unclear, but the changes in immune modulation that occur after transplantation are likely to play a key role. We describe 4 patients who developed brachial plexopathy (3 cases) or multiple lumbosacral radiculopathies (1 case) between 5 days and 4 months after autologous peripheral blood stem cell (3 cases) or allogeneic bone marrow transplantation without evidence of graft-versus-host disease (1 case). Infectious, tumor-related, toxic, and metabolic causes were excluded in all cases. Recovery was limited in two cases and nearly complete in the other two patients. Brachial plexopathies and polyradiculopathies are potential complications of peripheral blood stem cell and bone marrow transplantation. It is possible that these disorders may be the result of autoimmune phenomena directed against specific nerve antigens.

Bone Marrow Transplantation↗

PubMed2003

Posttransplantation thrombotic thrombocytopenic purpura: a single-center experience and a contemporary review.

OBJECTIVE: To assess the activity of von Willebrand factor-cleaving protease (vWF-CP) in patients with thrombotic thrombocytopenic purpura (TTP) complicating bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT). PATIENTS AND METHODS: From March 1, 1999, to June 30, 2001, allogeneic and autologous hematopoietic stem cell transplantation was performed in 118 and 400 patients, respectively. We reviewed risk factors for development of posttransplantation TTP and measured vWF-CP activity during active TTP in 10 recipients. RESULTS: The incidence of TTP after allogeneic and autologous transplantation was 6.8% (8/118) and 0.25% (1/400), respectively. Among the allogeneic transplant recipients, the incidence of TTP after nonmyeloablative (NMA) PBSCT, matched unrelated donor BMT, and sibling BMT or PBSCT was 15.4% (2/13), 11.8% (2/17), and 4.5% (4/88), respectively. Of the 10 patients with TTP, 9 (90%) had received extensive prior therapy, including autologous transplantation in both NMA recipients. Acute graft-vs-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate in most affected patients. The vWF antigen level was elevated in all patients, and no patients showed evidence of vWF-CP deficiency. During active TTP, 6 patients had grade II-IV acute GVHD, 1 had extensive chronic GVHD, and 4 had cytomegalovirus viremia. Risk factor analysis for development of TTP showed that transplant type (NMA and matched unrelated donor) and source of stem cells (bone marrow vs peripheral blood stem cell) were significant. CONCLUSIONS: Posttransplantation TTP was not found to be associated with severe vWF-CP deficiency. The elevated levels of vWF antigen are consistent with diffuse endothelial injury likely because of multiple interacting factors such as extensive prior therapy, GVHD, cyclosporine, and reactivation of cytomegalovirus. The disorder appears to be more frequent among patients with, or at risk for, acute GVHD, suggesting a possible role in the pathogenesis. Nonmyeloablative transplantation does not appear to confer a lesser risk, possibly for these reasons.

ADAM Proteins↗

PubMed2002

Stem cell transplantation for the management of primary systemic amyloidosis.

PURPOSE: To review the characteristics and outcomes of amyloidosis patients treated with high-dose chemotherapy and stem cell reconstitution. SUBJECTS AND METHODS: Sixty-six patients with biopsy-proven amyloidosis received transplants between March 1996 and January 2001. All patients had evidence of a clonal plasma cell dyscrasia; those with nonimmunoglobulin forms of amyloidosis were excluded, as were those who had no symptoms of amyloidosis, purpura, carpal tunnel syndrome, or symptomatic multiple myeloma. RESULTS: Amyloid was seen clinically in the kidneys (n = 45 patients), heart (n = 32), peripheral nerves (n = 11), and liver (n = 11). A monoclonal protein was found in the serum in 46 patients and in the urine in 57 patients. The median daily urinary protein loss was 4.1 g. Septal thickness, measured by echocardiography, ranged from 7 to 24 mm (median, 12 mm); 8 patients had a septal thickness > or =16 mm. Ten patients received transplants 1 year or more after diagnosis. All patients received melphalan-based chemotherapy; 17 patients were conditioned with total body irradiation. Nine patients required dialysis, 7 of whom died. Treatment-related mortality for stem cell transplantation was 14% (9/66). After a median of 25 months of follow-up after transplantation, the percentage of patients alive with one organ involved was 91% (31 of 34); two organs, 82% (18 of 22); three organs, 33% (3 of 9); and four organs, 0% (0 of 1). Hematologic responses were seen in 33 patients and organ responses in 32 patients. The 2-year actuarial survival of all patients was 70%. CONCLUSION: The number of organs involved before stem cell transplantation for amyloidosis is the most important factor in predicting subsequent survival. Stem cell transplantation should be considered as a treatment option for selected patients with amyloidosis.

Adult↗

PubMed2002

Early lymphocyte recovery post-autologous haematopoietic stem cell transplantation is associated with better survival in Hodgkin's disease.

A retrospective study of 82 patients was conducted to determine the relationship of absolute lymphocyte count (ALC) recovery with clinical outcome after autologous stem cell transplantation (ASCT) in Hodgkin's disease (HD). The median overall (OS) and progression-free survival (PFS) times from the day of transplantation were significantly better for the 41 patients with ALC > or = 0.5 x 10(9) cells/l compared with the 41 patients with ALC < 0.5 x 10(9) cells/l ("not yet reached" versus 42 months, P < 0.0001; 57 versus 15 months, P < 0.002 respectively). Thus, ALC recovery on day 15 post ASCT in HD is associated with better survival and requires further study.

Adolescent↗

PubMed2002

Veno-occlusive disease of the liver after blood and marrow transplantation: analysis of pre- and post-transplant risk factors associated with severity and results of therapy with tissue plasminogen activator.

We reviewed our blood and marrow transplantation (BMT) database from April 1982 to July 1996 and identified 111 of 474 patients with serum bilirubin concentration (SBR) > or = 34 micromol/l for two consecutive days within the first 20 days after related allogeneic or autologous BMT. Of the 111, 73 fulfilled the Seattle criteria for veno-occlusive disease of the liver (VOD) and had no other obvious cause for liver dysfunction. The patients were 16-60 years old (median, 39 years), and 41 were male (56%). Fourteen patients (19%) had autologous BMT, and 59 (81%) had allogeneic BMT. Twenty-eight (38%), 12 (16%), and 33 (45%) patients had severe, moderate, and mild VOD, respectively, by Seattle criteria. None of 23 patients with maximum (max) SBR > or = 257 micromol/l survived, all patients with max SBR < or = 128 micromol/l survived, and 7 of 15 patients (47%) with max SBR 128-257 micromol/l survived. The only pre-transplantation risk factor predictive of severe VOD was advanced disease state (P = 0.035), and the only transplant factors that predicted severe VOD were max SBR (P = 0.01) and maximum blood urea level (P = 0.03). Ten patients (all with creatinine levels > or = 150 micromol/l) were treated with tissue plasminogen activator; only two had a significant response and only one survived beyond day 120.

Adolescent↗