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1.
J Clin Pathol ; 61(5): 681-3, 2008 May.
Article in English | MEDLINE | ID: mdl-18441161

ABSTRACT

Spinal cord compression from extramedullary haemopoiesis within the spinal epidural space is a rare complication of myelofibrosis and polycythaemia rubra vera (PRV). A 69-year-old male with PRV (later transforming to myelofibrosis) who developed this complication is described here. Due to the uncertainty over its optimal treatment, previous case reports were systematically reviewed to define its presentations, treatments and outcomes. Including the present case this complication has been reported in 21 patients with myelofibrosis and PRV: 17 were male and the mean symptom duration was 7.6 months. Neurological improvement occurred in 14 patients and 12 survived. Seventy-five per cent of patients receiving combined treatment (irradiation with laminectomy or chemotherapy) showed neurological improvement and 100% survived. In contrast, 67% of those receiving single treatments exhibited improved neurology and only 33% survived. It is concluded that spinal cord compression in myelofibrosis and PRV has a high mortality, with combined treatment providing a better prognosis.


Subject(s)
Polycythemia Vera/complications , Primary Myelofibrosis/complications , Spinal Cord Compression/etiology , Adult , Aged , Combined Modality Therapy , Female , Hematopoiesis, Extramedullary , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Spinal Cord Compression/diagnosis , Spinal Cord Compression/therapy
2.
Ann Oncol ; 19(3): 570-6, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18056649

ABSTRACT

BACKGROUND: The purpose of this study was to determine whether there was a relationship between disease activity and health functioning, as measured by a range of patient-reported outcome (PRO) measures in patients with follicular lymphoma (FL). PATIENTS AND METHODS: A total of 222 patients with FL were recruited from eight sites across the UK and they completed a number of PRO measures. The participants were analyzed across five disease states: 'active disease-newly diagnosed', 'active disease-relapsed', 'partial response', 'complete response' and 'disease free'. The relationship between these disease states and their level of health functioning was assessed as well as the relationship between being 'on' or 'off' chemotherapy and disease state. RESULTS: In terms of health-related quality of life (HRQoL), participants in the relapsed category had the lowest mean physical well-being, emotional well-being, functional well-being and social well-being score. In a regression analysis, the 'active disease-relapsed' group acted as a significant predictor for each PRO variable. In addition, the remission group acted as a significant predictor of high anxiety scores as measured by the Hospital Anxiety and Depression Scale. CONCLUSION: The results of this study demonstrate that various aspects of patient-reported health outcomes differ according to disease state in patients with FL. For those patients who have relapsed, they are more likely to experience worse HRQoL and other patient-reported health outcomes than patients newly diagnosed, in partial or complete remission or when completely disease free.


Subject(s)
Anxiety/epidemiology , Depression/epidemiology , Lymphoma, Follicular/classification , Lymphoma, Follicular/epidemiology , Quality of Life , Adult , Aged , Aged, 80 and over , Comorbidity , Employment/statistics & numerical data , Female , Humans , Lymphoma, Follicular/therapy , Male , Middle Aged , Regression Analysis , Treatment Outcome , United Kingdom/epidemiology
3.
Bone Marrow Transplant ; 37(5): 455-61, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16435017

ABSTRACT

Reduced intensity conditioning (RIC) for allogeneic stem cell transplantation allows stable donor cell engraftment with the maintenance of a graft versus malignancy effect. Many different regimens exist employing various combinations of chemotherapy, radiotherapy and T-cell depletion. We examined the role of non-T-cell depleted RIC regimens in 56 patients with haematological malignancies. Patients received fludarabine phosphate for 5 days (30 mg/m2 in 35 patients, 25 mg/m2 in 21 patients) and melphalan for 1 day (140 mg/m2 in 36 patients, 100 mg/m2 in 20 patients). Immunosuppression was with CyA alone in 33 patients and CyA/MTX in 23 patients. Twenty-four of the 26 patients with chimerism data showed >95% donor chimerism at 3 months post transplant. aGVHD occurred in 18% of patients receiving CyA/MTX compared to 53% of patients receiving CyA. The 100-day mortality rate was 0.16 (95%CI 0.08-0.28) and 1-year nonrelapse mortality was 0.24 (95%CI 0.13-0.38). Thirty-three patients remained alive and in CR at a median of 19 months post transplant (range 3-38 months). We have shown that patients transplanted with fludarabine phosphate, melphalan 100 mg/m2 and with CyA/MTX as post transplant immunosuppression can achieve good disease control with an acceptable level of toxicity. Further studies are required to confirm these findings.


Subject(s)
Graft vs Tumor Effect , Hematopoietic Stem Cell Transplantation/methods , Melphalan/administration & dosage , Transplantation Conditioning/methods , Vidarabine Phosphate/analogs & derivatives , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Child, Preschool , Female , Graft vs Host Disease , Hematologic Neoplasms/mortality , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/mortality , Humans , Immunosuppression Therapy/methods , Infant , Male , Middle Aged , Transplantation Chimera , Transplantation, Homologous , Treatment Outcome , Vidarabine Phosphate/administration & dosage
4.
J Infect ; 47(4): 344-7, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14556761

ABSTRACT

Endocarditis secondary to Aspergillus niger has not been described in a leukaemic patient. We describe a case of A. niger endocarditis in a patient with acute myeloid leukaemia and refractory fever. The microbiological cause of his endocarditis was initially misdiagnosed because he fulfilled the Duke criteria for enterococcal endocarditis. A polymerase chain reaction test utilizing pan-fungal primers detected a product from an Aspergillus sp. The DNA was subsequently sequenced and was found to have 100% homology with A. niger. A postmortem revealed fungal endocarditis secondary to disseminated aspergillosis, without evidence of bacterial endocarditis. The patient was found to have a lung aspergilloma that was possibly occupationally acquired, and may have been long standing.


Subject(s)
Aspergillosis/diagnosis , Aspergillus niger/isolation & purification , Endocarditis/diagnosis , Endocarditis/microbiology , Leukemia, Myeloid, Acute/complications , Polymerase Chain Reaction/methods , Aspergillosis/microbiology , DNA, Fungal/analysis , Fatal Outcome , Humans , Male , Middle Aged
5.
Int J Oncol ; 22(2): 421-4, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12527943

ABSTRACT

The aim of this study was to determine whether administration of BB-10010, a synthetic stem cell inhibitor, would allow more intensive chemotherapy to be administered to patients with newly diagnosed high grade NHL. Thirteen patients were randomised to receive BB-10010 concurrently with dose-intensified BEMOP/CA chemotherapy (7 patients) or chemotherapy alone (6 patients). Although the mean neutrophil count of BB-10010 treated patients was higher following cycles 1, 2 and 3 of chemotherapy compared with those receiving chemotherapy alone, there was no difference in the mean number of cycles tolerated, blood component usage and hospital admissions due to infections. No specific toxicity of BB-10010 was identified. Whilst BB-10010 can be administered safely, it does not improve the ability of patients to tolerate intensive chemotherapy for high grade NHL.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Growth Inhibitors/therapeutic use , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Non-Hodgkin/drug therapy , Macrophage Inflammatory Proteins/therapeutic use , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cell Division/drug effects , Chemokine CCL3 , Chemokine CCL4 , Female , Growth Inhibitors/adverse effects , Hematopoietic Stem Cells/drug effects , Humans , Lymphoma, T-Cell/drug therapy , Male , Middle Aged , Neutropenia/chemically induced , Neutropenia/prevention & control , Safety , Thrombocytopenia/chemically induced , Thrombocytopenia/prevention & control , Treatment Failure
6.
J Clin Oncol ; 16(10): 3257-63, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9779699

ABSTRACT

PURPOSE: CAMPATH-1H is a human immunoglobulin G1 (IgG1) anti-CD52 monoclonal antibody (MAb) that binds to nearly all B-cell and T-cell lymphomas. We report here the results of a multicenter phase II trial of CAMPATH-1H in patients with advanced, low-grade non-Hodgkin's lymphoma (NHL) who were previously treated with chemotherapy. PATIENTS AND METHODS: Fifty patients who had relapsed (n=25) after or were resistant (n = 25) to chemotherapy were treated with CAMPATH-1H 30 mg administered as a 2-hour intravenous (i.v.) infusion three times weekly for a maximum period of 12 weeks. RESULTS: Six patients (14%) with B-cell lymphomas achieved a partial remission (PR). Patients with mycosis fungoides appeared to respond more frequently (50%; four of eight patients, which included two complete remissions [CRs]). Lymphoma cells were rapidly eliminated from blood in 16 of 17 patients (94%). CR in the bone marrow was obtained in 32% of the patients. Lymphoma skin lesions disappeared completely in four of 10 patients and partial regression was obtained in three patients. Lymphadenopathy and splenomegaly were normalized in only 5% and 15% of patients, respectively. Lymphopenia (< 0.5 x 10(9)/L) occurred in all patients. World Health Organization (WHO) grade IV neutropenia occurred in 14 patients (28%). Opportunistic infections were diagnosed in seven patients and nine patients had bacterial septicemia. Death related to infectious complications occurred in three patients. CONCLUSION: CAMPATH-1H had a significant but limited activity in patients with advanced, heavily pretreated NHL. The most pronounced effects were noted in the blood and bone marrow and in patients with mycosis fungoides. The risk for serious infectious complications needs to be considered for severely ill patients who are evaluated for CAMPATH-1H treatment.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antibodies, Neoplasm/therapeutic use , Antineoplastic Agents/therapeutic use , Lymphoma, Non-Hodgkin/therapy , Adult , Alemtuzumab , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Antibodies, Neoplasm/administration & dosage , Antibodies, Neoplasm/adverse effects , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Drug Administration Schedule , Female , Humans , Infusions, Intravenous , Lymphoma, B-Cell/therapy , Male , Mycosis Fungoides/therapy , Remission Induction
7.
Bone Marrow Transplant ; 22(3): 281-4, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9720743

ABSTRACT

Hepatic veno-occlusive disease (VOD) of the liver is a common complication following high-dose cytotoxic therapy for bone marrow transplantation (BMT). The major pathological changes are seen in centrilobular (zone 3) hepatocytes and adjacent endothelium. Glutathione (GSH) becomes depleted following chemotherapy and experimental evidence suggests reduced levels predispose to centrilobular hepatocyte and endothelial cell injury. Animal studies have shown that glutamine infusions can maintain GSH levels and protect against free radical injury. We have prospectively studied the effect of glutamine supplementation during BMT. Thirty-four patients undergoing BMT were randomised to receive either glycl-L-glutamine (n = 18) or an isonitrogenous mixture of non-essential amino acids (n = 16). Glutamine was shown to significantly preserve protein C (days +4 and +7, P < 0.05) and albumin levels (days 0 and +4, P < 0.02). Markers of thrombin and plasmin generation (thrombin-antithrombin, prothrombin fragment F1+2 and plasmin-antiplasmin levels) were not significantly changed between the two groups. These findings suggest that glutamine preserves hepatic function but does not alter thrombin or plasmin generation during BMT. Previous studies have shown reductions in protein C, albumin, factor X and factor VII levels post BMT. Falling protein C levels have been shown to be predictive of severe VOD. These data suggest a role for glutamine in the protection of hepatic function following BMT.


Subject(s)
Bone Marrow Transplantation/methods , Dipeptides/administration & dosage , Liver/drug effects , Adolescent , Adult , Animals , Bone Marrow Transplantation/adverse effects , Bone Marrow Transplantation/physiology , Double-Blind Method , Female , Fibrinolysin/biosynthesis , Glutathione/metabolism , Hepatic Veno-Occlusive Disease/prevention & control , Humans , Infusions, Parenteral , Leukemia/therapy , Liver/physiology , Lymphoma/therapy , Male , Middle Aged , Prospective Studies , Protein C/metabolism , Serum Albumin/metabolism , Thrombin/biosynthesis
8.
Bone Marrow Transplant ; 21(8): 829-32, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9603409

ABSTRACT

Hepatic veno-occlusive disease (VOD) of the liver is a common complication following high-dose cytotoxic therapy for bone marrow transplantation (BMT). Liver injury is believed to occur following free radical damage to endothelial cells of the sinusoids and small hepatic veins. Glutathione the main antioxidant of the cytosol becomes depleted following chemotherapy. Animal studies have shown that glutamine infusions can maintain glutathione levels and protect against free radical injury. We present two cases of established VOD successfully treated with intravenous glutamine (as dipeptide) and oral vitamin E. Although both cases have possible confounding factors we believe that these give support to the notion that glutamine/vitamin E may have a role in the prophylaxis and treatment of VOD. Further formal trials are indicated.


Subject(s)
Antineoplastic Agents/adverse effects , Glutamine/administration & dosage , Hepatic Veno-Occlusive Disease/drug therapy , Vitamin E/administration & dosage , Adult , Humans , Male
11.
13.
Br J Haematol ; 88(3): 472-80, 1994 Nov.
Article in English | MEDLINE | ID: mdl-7529529

ABSTRACT

We have measured the in vitro growth requirements of progenitor cells released into the blood of cancer patients following administration of chemotherapy and cytokines. In order to distinguish the direct effects of cytokines on progenitors from those activating accessory cells, we have compared clonogenic growth before and after CD34-positive selection of progenitors, in serum-free conditions. CD34 selection had little effect on the cytokine requirements of erythroid colony-forming cells and single cytokines, particularly interleukin-3, could support considerable colony growth in both mononuclear and CD34+ cell suspensions. Optimal erythroid colony growth, however, usually required the addition of a combination of stem cell factor and interleukin-3, in addition to erythropoietin, which was always required. Maximal numbers of granulocyte-monocyte progenitors in mononuclear cell cultures, could be achieved with a mixture of stem cell factor, interleukin-3 and granulocyte-monocyte colony stimulating factor. However, after CD34 selection, full myeloid colony growth was only achieved when granulocyte colony stimulating factor was added to the above mixture. This presumably reflects loss of accessory cells, during CD34 selection, which produce this cytokine. When transplanted after 8 d of culture, 16/22 myeloid colonies from erythropoietin-free cultures of peripheral blood stem cell harvests, could generate secondary erythroid colonies implying that these progenitors are multipotential. However, surface marker analysis of individual erythroid colonies revealed only the occasional presence of granulocytes and monocytes. These data demonstrate that cytokine mixtures are required for optimal colony growth, particularly after CD34 selection, and that most mobilized, blood clonogenic cells are multipotential.


Subject(s)
Erythroid Precursor Cells/physiology , Granulocyte-Macrophage Colony-Stimulating Factor/physiology , Hematopoietic Stem Cells/physiology , Interleukin-3/physiology , Macrophage Colony-Stimulating Factor/physiology , Antigens, CD/physiology , Antigens, CD34 , Hematopoietic Stem Cell Transplantation/methods , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , In Vitro Techniques , Multiple Myeloma/blood , Paraproteinemias/blood
14.
Eur J Clin Invest ; 23(9): 540-5, 1993 Sep.
Article in English | MEDLINE | ID: mdl-8243524

ABSTRACT

Endotoxin was measured in over 1000 plasma samples from bone marrow transplant patients in a randomized trial of the IgM-enriched intravenous immunoglobulin (IVIG) Pentaglobin. Peak endotoxaemia was significantly reduced (P = 0.02) in patients receiving Pentaglobin and 70% of all pyrexias of unknown origin were associated with endotoxaemia. Gut mucosal damage, assessed by lactulose/mannitol ratios, was significantly associated (P = 0.02) with endotoxaemia. Specific IgM antibody to endotoxin core-glycolipid was significantly raised (P < 0.01) in patients receiving the IVIG, and the IgM fraction of Pentaglobin was found to contain most of the anti-endotoxin antibody activity of the IVIG. These results suggest a role for IgM-enriched IVIG as a prophylactic agent for the reduction of endotoxaemia and its consequences in bone marrow transplant patients.


Subject(s)
Antibodies, Anti-Idiotypic/blood , Bacterial Infections/drug therapy , Bone Marrow Transplantation , Endotoxins/blood , Immunoglobulin A/therapeutic use , Immunoglobulin M/therapeutic use , Adolescent , Adult , Bacterial Infections/blood , Bacterial Infections/etiology , Female , Humans , Male , Middle Aged
17.
Cancer ; 70(2): 476-83, 1992 Jul 15.
Article in English | MEDLINE | ID: mdl-1319817

ABSTRACT

BACKGROUND: Regressing atypical histiocytosis is a rare multifocal cutaneous tumor characterized by large, spontaneously regressing, ulcerating skin nodules. Although initially self-remitting, the condition may progress to systemic lymphoma. METHODS: Using material from one patient, an attempt was made to clarify the nature of this condition with immunophenotyping, genotyping, and chromosome studies. RESULTS: Immunophenotyping studies indicated the condition was of T-cell lineage, although T-cell receptor gene studies showed polyclonal rearrangement. This case progressed to systemic lymphoma. CONCLUSIONS: The authors believe regressing atypical histiocytosis is a regressing phase of Ki-1-positive anaplastic large cell lymphoma of the skin.


Subject(s)
Antigens, CD/metabolism , Antigens, Neoplasm/metabolism , DNA, Neoplasm/metabolism , Histiocytosis/pathology , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, T-Cell, Cutaneous/pathology , Neoplasm Regression, Spontaneous/pathology , RNA, Neoplasm/metabolism , Skin Diseases/pathology , Skin Neoplasms/pathology , Adult , Female , Gene Rearrangement, T-Lymphocyte , Humans , Immunohistochemistry , Immunophenotyping , Karyotyping , Ki-1 Antigen , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/immunology , Lymphoma, T-Cell, Cutaneous/genetics , Lymphoma, T-Cell, Cutaneous/immunology , Neoplasm Regression, Spontaneous/genetics , Neoplasm Regression, Spontaneous/immunology , RNA, Messenger/metabolism , Remission, Spontaneous , Skin Neoplasms/genetics , Skin Neoplasms/immunology
18.
Bone Marrow Transplant ; 9(6): 451-7, 1992 Jun.
Article in English | MEDLINE | ID: mdl-1628130

ABSTRACT

In a study of 63 allogeneic and autologous bone marrow transplants, patients were randomized to receive the IgM and IgA enriched intravenous immunoglobulin (IVIG) preparation (Pentaglobin). Pentaglobin has been postulated to have anti-endotoxin properties and one of the aims of the study was to measure endotoxin levels in these patients together with the clinical sequelae of infection. The anti-endotoxin effects of Pentaglobin were found to reside in the IgM fraction. Those patients who received Pentaglobin were significantly protected from dying from infection in the first 100 days after the transplant, although it was not actually possible to document bacterial infections as the cause of death in the control patients. Peak endotoxin levels were significantly reduced (p = 0.02) in those patients receiving Pentaglobin. Liver damage as assessed by liver enzyme abnormalities correlated significantly with the presence of endotoxaemia greater than 25 pg/ml and up to 70% of pyrexial episodes were associated with endotoxaemia. Our results suggest that Pentaglobin is useful in reducing hepatic toxicity and this may be related to a reduction in endotoxaemia.


Subject(s)
Bacterial Infections/therapy , Bone Marrow Transplantation , Endotoxins/blood , Immunoglobulin A/therapeutic use , Immunoglobulin M/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Adolescent , Adult , Bacterial Infections/etiology , Bone Marrow Transplantation/mortality , Cause of Death , Female , Humans , Liver Diseases/blood , Liver Diseases/etiology , Male , Middle Aged
19.
Br J Haematol ; 81(1): 12-7, 1992 May.
Article in English | MEDLINE | ID: mdl-1520610

ABSTRACT

Erythroid regeneration is an important and separate element in the engraftment process in allogeneic and autologous bone marrow transplantation (alloBMT, autoBMT). Qualitative visual reticulocyte counting has proved inadequate in the evaluation of erythropoiesis after BMT but automated flow cytometry now allows the reliable quantitation of reticulocytes even to very low levels. Reticulocyte counts and highly fluorescent reticulocyte (HFR) counts (very early reticulocytes) were estimated daily in recipients of 22 autoBMT and 14 alloBMT using a Sysmex R-1000 automated reticulocyte counter. Marrow ablation caused an immediate and rapid fall in both the reticulocyte count and the HFR. Measurable numbers of reticulocytes persisted throughout the hypoplastic period, but HFR fell to zero in the majority of both the autoBMT and alloBMT. HFR rose significantly after a median time of 14 d post-autoBMT, and 12 d post-alloBMT. Attainment of 15 x 10(9)/l reticulocytes and 0.5 x 10(9)/l HFR at day 21 post-transplant was associated with ultimate engraftment in 100% cases. Inadequate engraftment was seen in the majority of patients whose responses fell below these levels. Graft-versus-host disease was associated with a transient slight reduction in reticulocyte count. Neither episodes of infection nor blood transfusions had any significant impact on trends of reticulocytes or HFR. Automated flow cytometric reticulocyte counting has been shown to provide an accessible measure of erythroid activity which may be of predictive value in the management of patients following bone marrow transplantation.


Subject(s)
Blood Cell Count/methods , Bone Marrow Transplantation/physiology , Erythropoiesis/physiology , Reticulocytes/cytology , Cell Division/physiology , Flow Cytometry , Humans , Reticulocytes/physiology , Transplantation, Autologous , Transplantation, Homologous
20.
Clin Oncol (R Coll Radiol) ; 4(1): 60-1, 1992 Jan.
Article in English | MEDLINE | ID: mdl-1736984

ABSTRACT

A case of intermittent superior vena cava syndrome caused by a Hickman catheter is reported. The symptoms resolved on removal of the catheter. The use of anticoagulants in conjunction with indwelling venous catheters is discussed.


Subject(s)
Catheterization, Central Venous/instrumentation , Catheters, Indwelling , Superior Vena Cava Syndrome/etiology , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Catheterization, Central Venous/adverse effects , Hodgkin Disease/drug therapy , Humans , Male , Middle Aged
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