Oral pilocarpine hydrochloride for the treatment of refractory xerostomia associated with chronic graft-versus-host disease.
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Administration, Oral↗
Biomedical subjects
J Treleaven
Publications and source records attributed to J Treleaven.
Relationship between donor-recipient blood group incompatibility and serum bilirubin after allogeneic bone marrow transplantation from HLA-identical siblings.
Data on 477 patients with hematologic malignancies undergoing allogeneic bone marrow transplantation from HLA-identical siblings were analyzed for correlation between donor-recipient ABO blood group incompatibility and the development of elevated bilirubin levels (over 17 mmol/l) after transplantation. The median bilirubin on day 15 after transplant and the maximum bilirubin in the first 100 days were significantly higher in 155 patients with ABO-mismatched donors compared with 322 patients with ABO-matched donors. In univariate analysis, age > 16 years (P = 0.000006), ABO incompatibility (P = 0.0004), a conditioning regimen other than cyclophosphamide-total body irradiation (P = 0.0005) and a diagnosis other than acute leukemia (P = 0.01) were associated with a higher probability of developing elevated bilirubin. Incidence of clinically diagnosed graft-versus-host disease (GVHD), and transplant-related mortality, relapse rates and overall survival were not influenced by ABO incompatibility. The hyperbilirubinemia was therefore unlikely to be the result of an increased incidence of hepatic complications such as GVHD or veno-occlusive disease. We suggest that studies on serious transplant-related complications such as GVHD and veno-occlusive disease which rely on bilirubin values for diagnosis should take donor-recipient ABO incompatibility into account.
Adolescent↗
Cytokine-mediated immunotherapy with or without donor leukocytes for poor-risk acute myeloid leukemia relapsing after allogeneic bone marrow transplantation.
Six patients with high-risk acute myeloid leukemia (AML) relapsing after allogeneic bone marrow transplantation (BMT) were treated with interferon-alpha 2b to stimulate graft-versus-leukemia reactions. Additionally, donor mononuclear cells were infused with or without interleukin-2 as first-line treatment or upon failure of interferon-alpha 2b in 5 patients. Two patients developed clinical acute graft-versus-host disease (GVHD) after a combination of donor leukocytes and interferon-alpha, and one developed de novo chronic GVHD after interleukin-2 and interferon-alpha. Complete remission was attained in 4 patients whereas 2 patients showed no response. Two of the responding patients relapsed rapidly. Four patients died of a combination of complications of immunotherapy and progressive disease. Two patients are alive in remission with chronic GVHD (Karnofsky performance scores of 80%) 8 and 18 months after immunotherapy. We conclude that cytokine-mediated immunotherapy with or without donor cell infusions may be effective in some cases of AML relapsing after allogeneic BMT, and may result in long-term survival. With limited data, it appears that development of chronic GVHD after immunotherapy is essential for continued remission.
Acute Disease↗
Peripheral blood stem cell transplantation may result in increased relapse of acute myeloid leukaemia due to reinfusion of a higher number of malignant cells.
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Acute Disease↗
Three weeks of ganciclovir for cytomegaloviraemia after allogeneic bone marrow transplantation.
Cytomegaloviraemia diagnosed by early antigen detection or conventional viral culture from blood occurred 7-71 days (median 41 days) after transplant in 25 of 38 consecutive patients undergoing bone marrow transplantation (BMT) from HLA-identical siblings for haematological malignancies where patient and/or donor were CMV-seropositive. Prophylactic ganciclovir, high-dose intravenous acyclovir or immunoglobulin were not administered. Viraemia was treated with a short 3-week course of ganciclovir (10 mg/kg x 1 week, 5 mg/kg x 2 weeks). Clearance of viraemia occurred 3-47 days (median 6 days) after starting anti-viral therapy in 20 patients (18 with ganciclovir, 2 with foscarnet), and before therapy in 3 patients. The remaining 2 patients received inadequate anti-viral therapy for various reasons and died of CMV pneumonitis. There was no clinical evidence of CMV disease in the 13 patients who did not develop viraemia. One patient treated with ganciclovir before adequate haematological recovery died of graft failure. A second episode of viraemia occurred in four patients, and a third in one. We conclude that a short 3-week course of ganciclovir is adequate in most patients developing cytomegaloviraemia after allogeneic BMT. Treatment is not necessary in all patients but some inadequately treated patients develop CMV disease. Ganciclovir is tolerated well but may cause severe myelosuppression if used prior to adequate marrow recovery.
Adolescent↗
Quantification of residual disease in Philadelphia-positive acute lymphoblastic leukemia: comparison of blood and bone marrow.
We designed a new semi-quantitative competitor-based PCR assay to assess the amount of p190 BCR-ABL mRNA in patients with Ph-positive ALL. Transcript numbers were compared in 29 paired specimens of blood and marrow collected contemporaneously from 18 patients at differing stages of disease. In general, the numbers of BCR-ABL transcripts detected in marrow in blood were not significantly different (p = 0.1). However, in four samples BCR-ABL transcripts (< 10-1000/micrograms RNA) were detected in the marrow while the blood was negative; the reverse, positive blood and negative marrow, was not seen. In a further three samples the number of BCR-ABL transcripts was more than 10-fold higher in the marrow. We measured the number of ABL transcripts/micrograms RNA in all samples as an internal standard in order to control for variations in sample quality and other parameters. For two out of the four discordant samples in which blood was PCR negative, the number of ABL transcripts/micrograms RNA detected in the marrow was substantially higher than in the blood, suggesting poor quality blood specimens. However, the ratio of BCR-ABL to ABL in marrow and blood was similar for the three discordant samples in which both tissues were PCR positive. We conclude that in general, blood and marrow contain similar BCR-ABL transcript numbers in Ph-positive ALL but some samples are discordant. Marrow is therefore the preferred tissue for residual disease studies. Quantification of ABL mRNA as an internal control is useful in the interpretation of competitive PCR data and may serve as a robust way to standardize results between laboratories.
Base Sequence↗
Use of erythropoietin in the management of the haemolytic uraemic syndrome induced by mitomycin C/tamoxifen.
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Adult↗
Cervical musculoskeletal dysfunction in post-concussional headache.
Persistent headache is a common symptom following a minor head injury or concussion, possibly related to simultaneous injury of structures of the cervical spine. This study measured aspects of cervical musculoskeletal function in a group of patients (12) with post-concussional headache (PCH) and in a normal control group. The PCH group was distinguished from the control group by the presence of painful upper cervical segmental joint dysfunction, less endurance in the neck flexor muscles and a higher incidence of moderately tight neck musculature. Active range of cervical motion and postural attitude were not significantly different between groups. As upper cervical joint dysfunction is a feature of cervicogenic causes of headache, the results of this study support the inclusion of a precise physical examination of the cervical region in differential diagnosis of patients suffering persistent headache following concussion.
Adolescent↗
Cimetidine-induced myelosuppression after bone marrow transplantation.
A strong temporal correlation was observed between cessation of cimetidine and a sustained increase in blood counts in two marrow transplant recipients. Both were receiving cimetidine from the day of transplantation for prophylaxis of stress ulceration and gastritis. The blood counts of both patients were not increasing satisfactorily 5-6 weeks after marrow transplantation without any obvious cause of marrow suppression. A similar observation has been made with the use of ranitidine after marrow transplantation suggesting that histamine H2-receptor antagonists should be used very cautiously, if at all, in the setting of bone marrow transplantation.
Adolescent↗
Idarubicin, high-dose cytarabine and etoposide for remission induction in therapy-related acute myeloid leukemia.
Five patients with therapy-related acute myeloid leukemia received combination induction chemotherapy with idarubicin, high-dose cytarabine, and etoposide. Complete remission was achieved in all patients with a single course of therapy. Treatment-related toxicity included nausea, vomiting, mucositis, diarrhea, and liver and kidney function abnormalities, and was low in all patients. There were no deaths during induction therapy. We conclude that this combination is well-tolerated in induction of remission in secondary acute myeloid leukemia, and warrants further assessment because of a very good complete remission rate.
Acute Disease↗
Fatal pneumococcal infections following allogeneic bone marrow transplant.
Six cases of fatal pneumococcal sepsis are described, occurring in the post-allograft setting, between 3 and 39 months after transplantation. Five of the six patients were suffering from chronic graft-versus-host disease and were receiving immunosuppressive therapy. Most were receiving prophylactic antibiotic therapy. This represents approximately 2% of the allograft population treated during the study period who survived for > 3 months after transplant. Pneumococcal sepsis is thus still a significant cause of death after allogeneic BMT and approaches to minimise its occurrence are discussed.
Acute Disease↗
Unusual infections following allogeneic bone marrow transplantation for chronic lymphocytic leukemia.
Unusually severe infections phenomena were observed in three patients with chronic lymphocytic leukemia (CLL) who had undergone allogeneic bone marrow transplantation (BMT) from matched sibling donors. The first developed three episodes of cytomegaloviremia requiring anti-viral therapy; the third episode accompanied by cytomegalovirus hepatitis which required prolonged therapy with foscarnet. Another had Listeria monocytogenes meningitis which was difficult to eradicate and required prolonged maintenance antimicrobial therapy with oral trimethoprim-sulfamethoxazole and intrathecal gentamicin until death due to chronic graft-versus-host disease. The third patient had cytomegaloviremia lasting 47 days, which did not clear within 4 weeks of full-dose ganciclovir. Although the number of patients is small, in our experience the problems encountered were unusually severe compared with patients allografted for other disease. We conclude that CLL patients undergoing allogeneic BMT may be at a higher risk of infectious complications than patients allografted for other diseases, and require careful monitoring.
Adult↗
Guillain-Barré syndrome after bone marrow transplantation.
A patient with chronic myeloid leukemia developed Guillain-Barré syndrome 4 months after allogeneic bone marrow transplantation. Clinical improvement occurred after a series of plasma exchanges. A relapse of the Guillain-Barré syndrome was also successfully treated with plasma exchange, with an eventual near-complete recovery. Reactivation of cytomegalovirus infection as manifested by antigenemia 2 months prior to the weakness was probably the precipitating event in this patient. We advocate early treatment of post-transplant Guillain-Barré syndrome with plasma exchange.
Adult↗
Bone marrow transplantation for primary refractory acute leukaemia.
Twenty-four patients with primary resistant acute leukaemia received bone marrow transplants (BMTs) from matched sibling, syngeneic, matched unrelated, or mismatched family donors as treatment for induction failure. Three (12.5%) patients are alive and well 2-10 years after transplantation. Four (16.7%) patients died of transplant-related complications early post-transplant and remission status could not be determined. Two patients did not achieve complete remission (CR) and died of cytomegalovirus pneumonitis 3 months post-transplant. One patient died of graft failure. CR was obtained in 17 of 20 (85%) evaluable patients after BMT. Ten of 17 (58.8%) patients achieving CR died of transplant-related complications 1-10 months post-transplant. Four of 17 (23.5%) patients who had achieved CR relapsed after transplant. We conclude that a high proportion of patients failing to achieve remission with aggressive conventional chemotherapy achieve CR with BMT and a small proportion become long-term survivors.
Adolescent↗
Graft failure after bone marrow transplantation from unrelated donors using busulphan and cyclophosphamide for conditioning.
Five patients received bone marrow allografts for leukaemia from serologically fully matched unrelated donors. The conditioning regimen was busulphan 16 mg/kg and cyclophosphamide (CY) 120 mg/kg. Engraftment was achieved in only two patients, with primary graft failure occurring in three patients. Two of the three patients with no evidence of myeloid engraftment on day 28 received GM-CSF without response. Both these patients required rescue with cryopreserved autologous material. Three patients remain alive, one died of relapse after a successful allograft and one died with pancytopenia. Although the number of patients is small, we conclude that the BuCY2 regimen with 120 mg/kg CY, while adequate for sibling allografts, may not be sufficiently immunosuppressive to permit consistent engraftment of bone marrow from unrelated donors.
Adult↗
Phenoxyethanol is effective topical therapy of gram-negative cellulitis in neutropenic patients.
In neutropenic patients cellulitis caused by Gram-negative organisms may prove difficult to control and cause considerable tissue damage. Phenoxyethanol has activity against a range of bacteria, including Pseudomonas aeruginosa, and is absorbed by intact skin. Three severely neutropenic patients are described in whom cellulitis failed to respond to appropriate intravenous antibiotics. However the topical application of phenoxyethanol solution gave prompt local control. This cheap and nontoxic agent may give dramatic improvement in this difficult clinical situation.
Administration, Topical↗
Arsenic and Ayurveda.
Manufacture of an Ayurvedic arsenic-containing compound is described, which is currently in use in India to control blood counts of patients with haematological malignancies. The efficacy and side effects of this compound are evaluated in the light of the fact that arsenic was recognised to be of use in the control of blood counts from patients with chronic myeloid leukaemia as long as 100 years ago, in the West.
Antineoplastic Agents↗
Results of a double blind placebo controlled study of ondansetron as an antiemetic during total body irradiation in patients undergoing bone marrow transplantation.
Total body irradiation (TBI) is a highly emetogenic component of the majority of conditioning regimens in use for bone marrow transplantation. Conventional antiemetic therapy fails to control nausea and vomiting induced by single fraction TBI in as many as 50% of patients. In a double blind study of 20 patients undergoing marrow transplantation, a single 8 mg ondansetron dose was compared with placebo given immediately prior to TBI. Our routine premedication of phenobarbitone and corticosteroid was also administered to all patients. All patients had received high dose melphalan the previous evening. Only 1 of the 10 patients in the ondansetron group experienced an emetic event compared with 5 of the 10 in the comparison group (p = 0.029). No significant adverse events were observed. Ondansetron appears to have extremely useful antiemetic activity during single fraction low dose rate TBI.
Adult↗