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H J Sutherland

Publications and source records attributed to H J Sutherland.

At least 55 records · Page 3Linked to original sources
PubMed1995

Prophylaxis for acute graft-versus-host disease following unrelated donor bone marrow transplantation.

Despite the use of conventional chemoprophylaxis regimens, patients receiving unrelated-donor BMT are at high risk of developing severe acute GVHD. We evaluated a prophylactic regimen combining CsA, MTX and anti-CD5-ricin A chain immunotoxin (H65-RTA) in 31 patients; pentoxifylline was also given to reduce the anticipated nephrotoxicity of CsA. In most cases, planned doses of CsA, MTX and H65-RTA were given (i.e. to 77%, 77% and 93% of patients, respectively). Although fluid retention requiring diuretic therapy was frequent, only 1 patient had a > 10% unexplained increase in body weight during the first 21 days post-BMT. Also, while significant increase of the baseline serum creatinine was noted in 7 patients, none required dialysis. One patient suffered a reversible allergic reaction to the immunotoxin; no other side effects attributable to this regimen were observed. All but 2 patients engrafted (1 died of fungemia on d + 19 and the other had persistent leukemia) and no late graft failures were observed. Seventeen patients developed acute GVHD grade > or = II (probability, 58% [95% CI 41-76%]); 7 had grade > or = III (probability, 24% [95% CI 12-43%]). In the 27 patients who achieved stable engraftment and have survived beyond d + 100, the 3-year probability of developing chronic GVHD was 66% (95% CI 48-84%). As of the last follow-up prior to 01 May 1994, 13 patients are alive in CR and one in relapse; 9 of these patients are off all immunosuppressives and well. Four other patients relapsed and died, and 13 died of other transplant-related causes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Treatment of myeloma using intensive therapy and allogeneic bone marrow transplantation.

Over a 5-year period we evaluated 65 myeloma patients aged < or = 55 years as potential candidates for intensive therapy and allogeneic BMT. Twenty six (40%) patients were transplanted; the median duration of disease was 4 months (range 2-58 months) and median number of prior regimens was 1 (range 1-5); all but five patients had chemosensitive disease. Conditioning regimens included combinations of BU+CY+MEL in 14 patients, BUCY2 in eight and CY+TBI in four. Donors were HLA-matched siblings in 19 cases, one antigen mismatched siblings in three and unrelated donors in four. All patients received CsA, plus either methylprednisolone (n = 5) or MTX with or without other agents (n = 19). Grade III or IV regimen-related toxicity (RRT) was relatively infrequent (3 patients) and was not seen in nine patients conditioned with BU (total dose 12 mg/kg) + MEL (100 mg/m2) + CY (90 mg/m2). Grade II-IV acute GVHD occurred in 20 patients, and was the cause of death in three. Chronic GVHD also caused three deaths. Thirteen of 21 evaluable patients (62%) achieved a CR and six achieved a PR. Actuarial progression-free survival (PFS) was 40% (95% confidence interval (CI) 19-61%) at a median follow-up of 14 months (range 3-56 months); the PFS was 52% (95% CI 24-74%) in chemoresponsive patients, compared with 0% in chemoresistant patients (P = 0.0066).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Allogeneic bone marrow transplantation for severe aplastic anemia: the Vancouver experience.

We report a retrospective analysis of the experience of a single centre in treating severe aplastic anemia (SAA) with allogeneic bone marrow transplant (BMT). Between 1982 and 1992, we transplanted 21 patients with SAA (14 males, 7 females); median age at BMT was 15 y (range 2-40 y); median time from diagnosis of SAA to BMT was 29 d (range 6 d-5.5 y). Thirteen patients had received multiple transfusions before BMT. Patients were conditioned with cyclophosphamide 50 mg/kg for 4 d, +/- total body irradiation 300-500 cGy as a single fraction; 1 patient received total nodal irradiation (750 cGy) plus antithymocyte globulin. Sixteen patients received bone marrow from human leucocyte antigen (HLA)-identical siblings, 3 from haplo-identical parents, and 2 from unrelated volunteer donors; graft-versus-host disease (GVHD) prophylaxis was variable. Three patients failed to fully engraft following BMT; 2 achieved successful engraftment following a second BMT. Six of 20 evaluable patients (30%) developed grade II-IV acute GVHD, of whom 3 died; 3 patients developed limited and 5 patients (31%) developed extensive chronic GVHD, of whom 1 died. Fourteen patients (67%) are alive and well following BMT with a median follow-up of 6 y (range 2.1-11 y). Survival was superior in patients receiving sibling-donor BMT (75%) compared with those receiving parent- or unrelated-donor BMT (40%). We conclude that allogeneic BMT remains an important mode of treatment for SAA, but long-term survival remains limited by graft failure and GVHD.

Adolescent↗
PubMed1994

Kinetics of committed and primitive blood progenitor mobilization after chemotherapy and growth factor treatment and their use in autotransplants.

Peripheral blood cells (PBCs) collected by leukapheresis after progenitor mobilization with chemotherapy and growth factors have been used successfully to replace marrow autografts in protocols requiring stem-cell support. Moreover, such transplants are often associated with more rapid recovery of blood cell counts than is routinely achieved with bone marrow. While conditions that mobilize colony-forming cells (CFCs) into the circulation are becoming increasingly well characterized, little information is available as to how these or other mobilizing treatments may influence the release of more primitive cells into the peripheral blood. To quantitate the peripheral blood content of such cells, we used the long-term culture-initiating cell (LTC-IC) assay, which detects a cell type that is able to produce progeny CFCs after a minimum of 5 weeks in cultures containing marrow fibroblasts. In this report, we present the findings on 21 patients who were transplanted over a 7-year period at our institution with PBCs alone. PBCs were collected in steady-state (n = 6) or during the recovery phase after high-dose cyclophosphamide (Cy; n = 15, nine with and six without additional growth factor administration). PBCs collected from another 11 patients given granulocyte colony-stimulating factor (G-CSF) were transplanted together with autologous marrow. Time-course studies of nine patients after Cy +/- granulocyte-macrophage CSF (GM-CSF) showed that CD34+ cells, CFCs, and LTC-ICs fell from normal to undetectable levels after Cy, and increased at the time of white blood cell (WBC) recovery: LTC-ICs to a mean of sixfold and CFCs to a mean of 26-fold higher than normal. The mean number of CD34+ cells, CFCs, and LTC-ICs present in the PBC harvest was twofold to 10-fold higher after mobilization than in steady-state collections; however, more than 2-log interpatient variability was observed. After PBC transplantation, the median time to a WBC count more than 10(9)/L was 12 days; polymorphonuclear leukocyte (PMN) count more than 0.5 x 10(9)/L, 15 days; and platelet count more than 20 x 10(9)/L, 17 days, although patients who received fewer than 1.5 x 10(5) CFCs/kg had a more than 50% chance of delayed count recovery (> 28 days). Patients who received Cy + GM-CSF-stimulated PBCs had more rapid and consistent platelet recoveries as compared with other groups receiving Cy mobilized or steady-state PBCs alone, and a rapid WBC recovery after Cy predicted a rapid WBC recovery after transplantation.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Separation↗
PubMed1994

Intensive therapy with cyclophosphamide, carmustine, etoposide +/- cisplatin, and autologous bone marrow transplantation for Hodgkin's disease in first relapse after combination chemotherapy.

The optimal timing in which to use intensive chemotherapy and autologous bone marrow transplantation (BMT) in Hodgkin's disease (HD) is uncertain. In 1985, we initiated a program in which this modality was used as the initial salvage therapy in patients relapsing after combination chemotherapy. Fifty-eight patients with HD in first relapse after primary chemotherapy received conditioning with high-dose cyclophosphamide, carmustine, etoposide (VP16-213) +/- cisplatin (CBV +/- P) followed by autologous BMT. All but six of these patients were given a median of two cycles of conventional chemotherapy +/- involved field radiation therapy before CBV +/- P and autologous BMT. These measures were not used as a means for patients selection; all patients receiving such therapy ultimately were transplanted. The probability of nonrelapse mortality, progression of HD, and progression-free survival post-BMT were calculated, and prognostic factors for progression-free survival were evaluated using the Cox proportional hazards method. Treatment-related deaths occurred in only three patients. Thirteen patients have relapsed at a median 0.7 years (range 0.1 to 3.5) post-BMT. At a median follow-up of 2.3 years (range 0.4 to 7.2), the actuarial progression-free survival is 64% (95% confidence interval, 46% to 78%). In the statistical analysis, three similarly weighted but independent prognostic factors were identified: "B" symptoms at relapse, extranodal disease at relapse, and initial remission duration of less than 1 year. Patients with no risk factors had a 3-year progression-free survival of 100%, compared with 81% in patients with one factor, 40% in those with two factors, and 0% in patients with all three factors. CBV +/- P and autologous BMT is highly effective salvage therapy for HD patients in a first relapse, particularly in the subset of patients with less than two adverse factors. Therapy must be improved in the future for patients with > or = 2 adverse factors.

Adolescent↗
PubMed1994

Opinion polling and decision making: a critical appraisal of quality of life assessment.

The relationship between quality of life (QOL) assessments and decision making, in relation to the delivery of health services, is subjected to critical appraisal. Three levels of decision making in the health care system are taken into account in the analysis. Criticisms of opinion polling provide the basis for the appraisal. Examples of criticisms considered are: Might the use of QOL information be manipulative? Could the interviews or questionnaires used to obtain QOL data influence personal opinions? Are the methods used sometimes defective and/or superficial? Will QOL information always be used in decision making in ways that are ascertainable and justifiable? It is concluded that the time has come for the main focus of critical appraisal in QOL research to shift, from an emphasis on evaluation of the quality of methods used for assessments of QOL, toward an emphasis on the practical usefulness of QOL data.

Decision Making↗
PubMed1994

Cytokines acting early in human haematopoiesis.

In long-term cultures (LTC) of human haematopoietic cells, primitive progenitors termed LTC-initiating cells can be maintained for several months and will differentiate to produce clonogenic cells and mature granulocytes and macrophages when provided with a supportive feeder layer of adherent mesenchymal cells. Primitive haematopoietic cells become associated with this feeder layer and their proliferative status and differentiation are regulated by their interaction with these feeder cells and the growth factors they produce. Both positive and negative regulators are generated in LTC and the balance between these diverse factors is readily manipulated by both direct and indirect mechanisms which appear to operate in a localized fashion. These features parallel those believed to characterize the mechanisms that regulate haematopoiesis in the bone marrow microenvironment in vivo and suggest that further analysis of the LTC system will be useful in delineating the full mystery of this process.

Cell Division↗
PubMed1994

Transplantation of patients with high risk acute myeloid leukemia in first remission with autologous marrow cultured in interleukin-2 followed by interleukin-2 administration.

Relapse rates in patients after autologous bone marrow transplantation (BMT) for acute myeloid leukemia (AML) continue to be high despite the use of aggressive conditioning regimens. Based on studies in the murine system a clinical protocol was developed that utilizes immunotherapy to obtain a graft-versus-leukemia (GVL) effect both pre-BMT (to purge leukemic cells from the autograft) and post-BMT (to eradicate residual leukemia in the patient). As part of a phase I study, 10 consecutive patients (median age 41 years, range 15-60 years) with 'high risk' AML (i.e. any of the following: FAB M5, WBC of > or = 50 x 10(9)/l at diagnosis or 'unfavorable' cytogenetic abnormalities) were transplanted at a median of 32 days (range 13-128 days) after achieving first remission. Marrow cells to be autografted were first cultured for 8 days at 37 degrees C in standard long-term culture medium (containing 12.5% horse serum, 12.5% fetal calf serum and 10(-6) M hydrocortisone) to which 1000 U/ml of interleukin-2 (IL-2) was also added. During this time patients received busulfan 4 mg/kg for 4 days and cyclophosphamide 60 mg/kg for 2 days). On the day of transplantation (day 0), the cultured marrow cells were collected from the flasks and infused over 1 h. Between days 0 and 7 patients were given escalating doses of subcutaneous IL-2 (2, 4 and 6 x 10(5) U/m2/day, 3-4 patients/dose level). Side-effects attributable to IL-2 were generally mild, dose-dependent and consisted of fever and malaise.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1993

Alternative mechanisms with and without steel factor support primitive human hematopoiesis.

As a first approach to defining the molecular requirements for supporting human hematopoietic stem cell maintenance and differentiation in vitro, we have analyzed and compared the ability of various factors to support the maintenance and initial differentiation of human long-term culture-initiating cells (LTC-ICs), a distinct, rare primitive hematopoietic cell type whose progeny after 5 weeks include cells detectable as colony-forming cells. Normal human marrow cells highly enriched in LTC-ICs (approximately 1% pure) were placed in cultures containing either preestablished, irradiated human marrow adherent feeder layers, or feeders consisting of Steel factor-deficient SI/SI, or normal +/+ murine fibroblasts, or no feeders. In some groups, either Steel factor alone, granulocyte colony-stimulating factor (G-CSF) and interleukin-3 (IL-3), or all three factors combined were also added repeatedly. SI/SI murine fibroblasts were equivalent to +/+ controls and to normal human marrow feeders in supporting both LTC-IC maintenance and clonogenic cell output over a 5-week period. Soluble Steel factor alone could, however, effectively substitute for human marrow feeders to support LTC-IC maintenance, although clonogenic cell output was markedly reduced under these conditions. Conversely, soluble Steel factor with G-CSF and IL-3 or with feeders (or all together) did not further enhance (or depress) LTC-IC maintenance, although under these conditions clonogenic cell output was markedly increased. These findings confirm previous evidence that LTC-IC maintenance and clonogenic cell production are differentially regulated and show for the first time that LTC-IC maintenance can be supported by different nonsynergizing factors that may, but need not, include Steel factor.

Animals↗
PubMed1993

Autografting in chronic myeloid leukemia with cultured marrow: update of the Vancouver Study.

When chronic myeloid leukemia (CML) marrow is set up in long-term culture (LTC), Philadelphia chromosome (Ph)-positive (Ph+) cells typically decline and Ph-negative (Ph-) hematopoietic cells often become detectable. In 1987, we initiated a study to evaluate the feasibility of using 10-day cultured marrow autografts to allow intensive treatment of CML. Patients were selected on the basis of a previous assessment of the frequencies of normal and leukemic LTC-initiating cells (LTC-IC) remaining in their marrow after 10 days of LTC. Of the 87 patients evaluated, 36 (41%) were considered eligible, and 22 (15 in first chronic phase [CP], Group 1; and 7 with more advanced disease, Group 2) were autografted with 10-day cultured marrow after intensive therapy. Satisfactory hematological recovery occurred in 16 patients, and of these, only Ph- cells were detected in 13 (nine in Group 1), with 76-94% Ph- cells in the other three (two in Group 1). Ph+ cells reappeared between 4 and 36 months post-autograft in all but one of the 13 patients in whom complete (morphological and cytogenetic) remission had been achieved; the remaining patient died in remission. Nine of these twelve patients were then treated with alpha-interferon (IFN-alpha) 1-3 x 10(6) units/m2, 3-7 days/week; four returned to complete remission, three developed increasing numbers of Ph+ cells, and two are still too early to evaluate. Fifteen patients (12 in Group 1) remain alive and well, nine in hematological remission (eight in Group 1), 9 to 64 months (median 28) post-autograft.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

A study of diet and breast cancer prevention in Canada: why healthy women participate in controlled trials.

Little research has been undertaken to determine why healthy people agree to enroll in randomized controlled trials of cancer prevention. This study describes the beliefs of Canadian women participating in a trial designed to determine the effect of reducing dietary fat on the development of breast cancer. Healthier eating, nutritional counseling, contributing to science, and helping others were the most frequently cited advantages of participation. Weight control and general better health were specifically associated with the dietary regimens. Attending appointments and difficulties when eating out were the main disadvantages of participation. Suggestions that would promote adherence to the trial protocol also were elicited. Responses cited most often included opportunities to meet other participants, more nutritional counseling (particularly psychological tips), updates about the trial, and more recipes. Attention should be paid to these suggestions as they characterize some of the major determinants of adherence behavior.

Adult↗
PubMed1993

Quality of life assessments and levels of decision making: differentiating objectives.

The purpose of this paper is to examine uses of quality of life (QOL) measurements at different levels of decision making within the health care system, ranging from the micro (clinical) level, through the meso (agency, institutional or regional) level to the macro and meta (governmental) levels. We use individualized, group and population-based QOL and preference assessments as illustrative examples of ways in which QOL information and decision making level interact. We conclude that the meso and macro levels pose particularly challenging problems, and suggest that, if the primary emphasis is placed on applications of QOL assessments at the micro (clinical) level of decision making, a research agenda that is much too limited may be adopted.

Chronic Disease↗
PubMed1993

Judging clinical research questions: what criteria are used?

The research question is a crucial aspect of every study. Criteria for the evaluation of the merit of the study question or hypothesis have received surprisingly little attention. A set of non-methodological criteria derived from interviews with 40 researchers (clinical investigators and laboratory scientists) is presented. For both types of researcher, the terms that best described the nature of the criteria included potential impact, justification, feasibility, track record, innovation, intuitive response, aesthetics and politics. The latter three criteria are notably subjective; however all the criteria have an element of non-objectivity. There may well be a reluctance to openly acknowledge that crucial choices about what scientific questions should be explored involve criteria which are themselves not 'objective', and indeed, not even 'scientific'.

Adult↗
PubMed1993

High-dose chemotherapy and autologous bone marrow transplantation for patients with poor prognosis nonseminomatous germ cell tumours.

Twenty-one patients with poor prognosis nonseminomatous germ cell tumours (six with extreme burden disease at presentation in whom partial remission had been achieved with initial induction therapy, and 15 with recurrent disease after induction therapy) were treated with high-dose chemotherapy and autologous bone marrow transplantation (BMT). The first six received etoposide 3.0 g m-2, ifosfamide 6.0 g m-2 and carboplatin 1.2 g m-2 (Regimen 1), and the subsequent 15 received etoposide 2.4 g m2 (continuous infusion), cyclophosphamide 7.2 g m-2 and carboplatin 0.8 g m-2 (Regimen 2) followed by infusion of previously stored autologous marrow. Regimen 1 was associated with considerable renal toxicity and mucositis, whereas Regimen 2 was relatively well tolerated. Two patients died as a consequence of the treatment: one of candidemia and one of interstitial pulmonary fibrosis. Only one of 17 patients who were autografted in or approaching marker remission subsequently developed disease progression (event-free survival 82%, 95% confidence interval [CI] 55% to 94%), whereas all four patients who had progressive disease at autografting subsequently developed further disease progression and died. Fourteen patients remain well and free of disease 0.5 to 6.5 years (median 3.3) post-BMT (event-free survival 67%, 95% CI 43% to 83%). A strategy of prompt reinduction followed by high-dose chemotherapy and autologous BMT at the first sign of failure of standard therapy may allow cure to be a realistic expectation.

Adolescent↗
PubMed1993

Do patients' evaluations of a future health state change when they actually enter that state?

Fundamental to using utilities for future health states for clinical decision analysis is the assumption that the utilities are stable. The purpose of this study was to determine if cancer patients' prior evaluations of a treatment-induced health state remain stable when they later experience that state. Before a four-week course of radiation therapy, 66 laryngeal cancer patients evaluated three common treatment-induced outcome scenarios (mild/moderate/severe) using rating scales and the time trade-off, and provided self-assessments of voice symptoms, voice function, and general health. Evaluations and self-assessments were repeated at the end of therapy, and respondents indicated which outcome scenario described their actual end-of-therapy state. Twenty-four patients identified the mild scenario as their outcome state, 36 the moderate, and 6 the severe. No across-time differences in evaluations were detected, although significant (P < .0001) downward shifts in scores for voice symptoms (t = 5.67), voice function (t = 5.10), and general health (t = 6.69) indicated that actual change in health status had occurred. These results imply that patients' evaluations of imagined short-term health states encountered during radiation therapy for laryngeal cancer remain consistent when those states are experienced at a later time. The design of this project provides a model for determining if this consistency appears in other clinical situations.

Activities of Daily Living↗
PubMed1993

Induction therapy for acute myelogenous leukemia in patients over 60 years with intermediate-dose cytosine arabinoside, mitoxantrone and etoposide.

Twenty-three patients greater than age 60 years with acute myelogenous leukemia (AML) received induction therapy with continuous infusion cytosine arabinoside (1.5 g/m2/day, day 1-3), mitoxantrone (10 mg/m2/day, day 1-3) and etoposide (800 mg/m2, day 4). Patients entering complete remission (CR) were eligible to receive an identical consolidation cycle. Eighteen of the 23 patients (78%; 95% confidence interval 56% to 93%) entered CR. Twelve of these received consolidation therapy and 4 of these remain in remission at 3 to 20 months. Hematologic toxicity of the regimen was acceptable; only 1 patient died following therapy (having attained a CR). Non-hematologic toxicity was mostly mild (grade 2 or less) with one episode of grade 3 cerebellar toxicity. While this regimen induces a high CR rate in patients > age 60 years, relapses remain common and overall survival is too early to assess.

Aged↗