Summary:Multiple oral complaints develop following high-dose chemo/radiotherapy and hematopoietic cell transplantation (HCT) which can influence quality of life. The purpose of this investigation was to assess quality of life, oral function, taste and smell in a cohort of patients following HCT. A general quality of life survey (the European Organization for Research and Treatment of Cancer (EORTC)) Quality of Life (QOL) questionnaire (QLQ-C30), with an added oral symptom and function scale and assessment of taste and smell was administered to a consecutive series of patients at day 90-100 post HCT. General QOL was impacted by fatigue, affecting physical, social emotional and cognitive function. While oral function scales appeared to be little affected at day 90-100 post HCT, abnormalities of taste were reported. Reports of changes in taste and smell appeared to parallel each other and changes remained at the time of the survey post-HCT. Change in taste appeared to be closely associated with dry mouth. Patients appeared to have difficulty in differentiating sour and bitter, which had been more affected than salt and sweet taste. Females appeared to report greater changes in taste than males. Increased smell sensitivity and taste change resulted in changes in food preparation in some cases, as did reported increase in sensitivity to sour and bitter taste. Acute complications are well known to affect QOL during the early period following HCT, but little assessment of long-term changes in oral QOL and taste has been conducted following transplant. The EORTC QLQ C-30 questionnaire with the oral addendum provides a measure of the quality of life and oral function, and may provide useful outcome measures for assessment of oral care prevention and management in HCT patients.
We analyzed the late outcomes of 429 long-term survivors post allogeneic hematopoietic SCT (allo-HSCT) who received transplant in our center between 1981 and 2002, and were free of their primary disease for X2 years after allo-HSCT. Late recurrent primary malignancy was found in 58 (13.5%) patients and was the primary cause of late death. A total of 37 (8.6%) patients died of nonrelapse causes at a median of 5.5 years (range, 2-15.6 years) post allo-HSCT. The major non-relapse causes of death were chronic GVHD (cGVHD), secondary malignancy and infection. The probabilities of OS and EFS were 85% (95% cumulative incidence (CI) (81-89%)) and 79% (95% CI (74-83%)) at 10 years, respectively. Long-term allo-HSCT survivors were evaluated for late complications (median follow-up, 8.6 years (range, 2.3-22.8 years)). cGVHD was diagnosed in 196 (53.1%) survivors. The endocrine and metabolic complications were hypogonadism in 134 (36.3%) patients, osteopenia/ osteoporosis in 90 (24.4%), dyslipidemia in 33 (8.9%), hypothyroidism in 28 (7.6%) and diabetes in 28 (7.6%). Hypertension was diagnosed in 79 (21.4%), renal impairment in 70 (19.0%), depression in 40 (10.8%) and sexual dysfunction in 33 (8.9%) survivors. We conclude that in patients who receive allo-HSCT as treatment for hematological malignancy and who are free of their original disease 2 years post transplant, mortality is low and the probability of durable remission is high. Lifelong surveillance is recommended.
Summary:While allogeneic stem cell transplantation (SCT) is curative for a significant number of patients with AML, relapse of disease within the bone marrow and/or extramedullary (EM) sites following high-dose therapy continues to limit the success of this treatment. Between October 1985 and December 1996, 81 adults underwent allogeneic SCT for de novo AML at our centre. Fortytwo patients remain alive and free of leukaemia with a median follow-up of 50 months. The 5-year actuarial event-free survivals (EFS) for all patients and for those undergoing SCT in CR1 or with advanced disease were 46% (95% confidence interval (CI) 34-58%), 63% (CI 46-76%), and 19% (CI 7-36%), respectively. Twentytwo patients relapsed at a median of 8 (range 1.6-54.5) months with the actuarial risk of relapse for all, CR1 and advanced disease patients being 38%, (CI 27-52%), 23% (CI 13-40%) and 68% (CI 46-88%), respectively. Ten patients relapsed at EM sites; six of these (27% of relapses) had an isolated EM relapse at a median of 31 (range 8.5-54) months. Three of the patients with isolated EM relapse survived у24 months following relapse and two patients remain disease-free at 29+ and 33+ months. BuCy conditioning followed by allogeneic SCT in AML results in satisfactory EFS although there is a significant risk of late isolated EM relapse. Keywords: acute myelogenous leukemia; extramedullary relapse; allogeneic BMT Allogeneic stem cell transplantation (SCT) is an effective therapy for patients with AML. 1-3 Long-term event-free survival (EFS) can be achieved in approximately 60% of patients undergoing SCT in first complete remission (CR1) 4-9 and 25-30% of those with more advanced disease. 1,2,4,10,11 However, there remains some controversy regarding the optimal transplant preparative regimen in AML. For patients transplanted in CR1, one randomized study demonstrated a regimen employing TBI to be superior to busulfan/cyclophosphamide (BuCy) conditioning, 7 while another showed the regimens to be equivalent. 8 One of the contributing factors to an unsuccessful result with SCT regardless of the preparative regimen utilized is relapse, occurring in 20-25% and 30-50% of AML patients transplanted during CR1 or with advanced disease, respectively. 1,2,4,7,9 The site of relapse after a TBI-based preparative regimen is usually the marrow with or without extramedullary (EM) disease. 12 Isolated EM relapse occurred in only 13% of patients developing recurrent disease after TBI conditioning in one study. 12 Little is known about the risk of isolated EM relapse of AML following BuCy with a small number of such patients reported recently in a survey by the European Group for Blood and Marrow Transplantation (EBMT) of more than 3000 AML transplants. 13 The present review was prompted by the observation that several patients receiving allogeneic SCT after BuCy at our institution experienced isolated EM relapse.
Cyclosporin A (CsA) absorption is highly variable in BMT patients. Neoral, a new microemulsion formulation of CsA, permits increased absorption with less variable pharmacokinetic parameters in non-BMT patients. We evaluated the pharmacokinetics of CsA after BMT in patients received microemulsion CsA. Two oral doses of 3mg/kg were given 48 h apart between 14 and 28 days after allogeneic BMT in 20 adults, and one dose in seven children, while subjects were receiving a continuous i.v. infusion of CsA. Whole blood samples were taken throughout the dosing interval to calculate the incremental CsA exposure using maximum concentration (Cmax), time to Cmax (tmax), concentration at 12 h after the dose (C12), the area under the concentration-time curve (AUC), and to establish inter- and intra-patient pharmacokinetic variability. Drug exposure was substantially lower in children than adults, with an AUC of 861+/-805 vs 2629+/-1487 micromg x h/l (P = 0.001), respectively, and absorption was delayed and diminished in both groups by comparison with solid organ recipients. Intra-patient variability in adults for AUC was high at 0.59+/-0.34, while inter-patient variability, measured as the coefficient of variation (c.v.), was 0.55 for the first and 0.54 for the second dose. In adults, gastrointestinal (GI) inflammation due to either mucositis or GVHD resulted in a higher AUC of 3077+/-1551 microg x h/l compared to 1795+/-973 microg x h/l (P = 0.02), and a similar trend was observed in children. AUC seemed little affected by the CsA formulation (liquid or capsule), or co-administration with liquids or food. Trough (12 h) CsA levels correlated poorly with incremental AUC. Sparse sample modeling of the AUC using two-point predictors taken at 2.5 and 5 h after dosing accurately approximated AUC in adults (r2 = 0.94), while 1.5 and 5 h was superior in children (r2 = 0.98). These data suggest that 12 h postdose trough measurements of CsA may not be the most appropriate way to evaluate CsA blood concentrations in order to establish therapeutic efficacy in BMT patients. Based on this study, the dose of microemulsion CsA should be adjusted based on recipient age, and the presence of GI inflammation secondary to mucositis or GVHD. These data would suggest that sparse sampling at time points earlier than the trough more accurately reflects the AUC and may correlate more closely with therapeutic efficacy early post-BMT.
Background: Curative intent chemotherapy for acute myelogenous leukemia (AML) leads to prolonged severe neutropenia, during which patients are highly susceptible to infection. Traditionally these high-risk patients were treated as inpatients. Our center recently implemented a selective ambulatory management policy for AML patients undergoing chemotherapy. Materials and methods:A retrospective analysis was conducted to assess the occurrence of septicemia in AML patients treated over a 5 years period with curative intent chemotherapy. This review encompasses a change in policy from primarily inpatient care to selective outpatient management coupled with prophylactic antibiotic therapy.Results: A total of 294 patients, receiving 623 cycles of chemotherapy were identified. A significant decrease in septicemia was observed from the inpatient to outpatient cohort (22% to 13% P < 0.05), which correlated with the shift towards outpatient treatment of consolidation cycles. A shift from Gram-negative to Gram-positive organisms as the cause of septicemia was also detected in the outpatient cohort, likely due to the introduction of ciprofloxacin prophylaxis. No significant emerging resistance and no septicemia-related mortality were noted in the outpatient cohort. Conclusion:The observed decrease in the incidence of septicemia in the ambulatory cohort adds supportive evidence to the feasibility of selective outpatient management of AML patients with respect to infectious complications.
A treatment strategy for adults with chemosensitive T-LBL that includes planned consolidation with SCT in first response produces favorable long-term outcome.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disease characterized by intravascular hemolysis, thrombophilia, and marrow failure. Its phenotype is due to absent or reduced expression of GPI-linked complement regulators and subsequent sensitivity of hematopoietic cells to complement-mediated damage and lysis. Introduction of the terminal complement inhibitor eculizumab drastically improved outcomes in PNH patients; however, despite this improvement, there remain several challenges faced by PNH patients and physicians who care for them. One of the most important is increasing awareness of the heterogeneity with which patients can present, which can lead to significant delays in recognition. Data from the Canadian PNH Registry are presented to demonstrate the variety of presenting symptoms. In Canada, geography precludes consolidation of care to just a few centers, so management is distributed across academic hospitals, linked together as the Canadian PNH Network. The Network over the last several years has developed educational programs and clinical checklists and has worked to standardize access to diagnostics across the country. Herein, we address some of the common diagnostic and therapeutic challenges faced by PNH physicians and give our recommendations.Gaps in knowledge are also addressed, and where appropriate, consensus opinion is provided. K E Y W O R D Saplastic anemia and bone marrow failure, bone marrow transplantation, coagulation disorders, red cell disorders | 37 PATRIQUIN eT Al.
Summary:Twenty-six patients with low-grade lymphoma (LGL) (n ؍ 18) or chronic lymphocytic leukemia (CLL) (n ؍ 8) received allogeneic BMTs between 1985 and 1998. Median age was 42 years, median interval from diagnosis to transplant 22 months and median number of prior treatments three. Twenty (77%) had stage IV disease; 22 (85%) had never achieved CR. Donor source was HLA matched sibling (n ؍ 19, 73%), matched unrelated (n ؍ 6, 23%) or syngeneic (n ؍ 1). Conditioning therapy included total body irradiation in 23 patients and busulphan in three. Twenty-five received GVHD prophylaxis with cyclosporine A; ؉ methotrexate (n ؍ 19), ؉ methylprednisolone (n ؍ 2) or ؉ T cell depletion of allograft ؎ methotrexate (n ؍ 4). Sixteen patients are alive, a median of 2.4 years post BMT. Death occurred due to transplant complications (n ؍ 7) or underlying disease (n ؍ 3). Eighteen (12 LGL, six CLL) of 22 evaluable patients (82%) achieved CR post BMT. Cumulative incidence of refractory/recurrent disease was 18% (95% confidence interval (CI) 7-42%). Overall and event-free survivals were 58% (95% CI 35-75%) and 54% (95% CI 32-72%), respectively. Allogeneic BMT for young patients with advanced LGL or CLL is feasible and can result in long-term disease-free survival. Bone Marrow Transplantation (2000) 25, 605-612. Keywords: low-grade lymphoma; chronic lymphocytic leukemia; allogeneic bone marrow transplantation Low-grade lymphoma (LGL) and chronic lymphocytic leukemia (CLL) are indolent hematologic malignancies with median survival times approaching a decade.1-5 Although clinical remission can be achieved with standard 6-9 and newer 10-14 therapies, prolonged freedom from recurrence has not been demonstrated for patients with advanced stage, making death from disease almost inevitable. 8,9,11,[13][14][15][16] for younger patients, particularly those with refractory or recurrent disease, a more aggressive approach to treatment can be justified. 17-20High-dose therapy with allogeneic stem cell support is an attractive option for such patients, where marrow involvement is common and the occurrence of a graftversus-leukemia/lymphoma (GVL) effect 21-26 may contribute to the achievement of long-term disease control. Worldwide experience with allogeneic transplantation in this setting is, however, still limited. We report results from 26 patients with LGL or CLL receiving allogeneic BMT at the Vancouver General Hospital since 1985. Patients and methods PatientsTwenty-six patients with LGL (n ϭ 18) or CLL (n ϭ 8) received allogeneic BMT between September 1985 and January 1998, during which time, a total of 589 allografts and 512 autografts were performed in adults by the Leukemia/BMT Program of British Columbia. Eligibility criteria included: (1) age р50-55 years (related donor) and р45-50 years (unrelated donor); (2) Karnofsky performance score (KPS) у80%; and (3) adequate pre-transplant organ function including left ventricular ejection fraction у40%, forced expiratory volume in 1 s у60% and diffusing capacity for car...
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