Reduced exercise capacity is associated with left ventricular systolic dysfunction in long-term survivors of allogeneic hematopoietic stem-cell transplantation.

PURPOSE: Exercise intolerance is a common complication in survivors of allogeneic hematopoietic stem-cell transplantation (allo-HSCT). The aim of this study was to determine if cardiac function measured with echocardiography is associated with exercise capacity measured with cardio-pulmonary exercise tests in long-term survivors treated in their youth with allo-HSCT. METHODS: The study included 96 patients, of which 54.2% were female, aged 34.9 ± 11.6 years and 17.7 ± 9.3 years after allo-HSCT. Reduced exercise capacity was defined as <85% of predicted-peak oxygen uptake (VO2peak ). Linear regression was used in the prediction of VO2peak (ml/kg/min). Receiver operating characteristic evaluated the accuracy of predicting reduced exercise capacity. RESULTS: VO2peak was 36.2 ± 7.7 ml/kg/min and 43 (44.8%) had reduced exercise capacity. Left ventricular ejection fraction was 55.4 ± 5.9% and global longitudinal strain (GLS) was -17.6% ± 2.0%. Left and right ventricular functions were significantly lower in survivors with reduced exercise capacity. Increased body mass index, lower physical activity score, reduced pulmonary function (by forced expiratory volume in 1-s) and reduced left ventricular systolic function (by GLS) were significant independent predictors for reduced VO2peak . GLS was superior to other echocardiographical indices for identifying reduced exercise capacity (area under curve = 0.64, p = 0.014). CONCLUSIONS: Left ventricular systolic dysfunction measured by GLS is associated with reduced exercise capacity in long-term allo-HSCT survivors.

Oral chronic GVHD after allogeneic stem cell transplantation without total body irradiation performed at a young age.

PURPOSE: Long-term survivors (LTSs) of allogeneic hematopoietic stem cell transplantation (allo-HCT) may experience oral long-term effects like chronic graft-versus-host disease (oral cGVHD). The aim of this study was to investigate oral cGVHD in patients treated at a young age (< 30 years) more than 5 years after allo-HCT without total body irradiation (TBI). METHODS: All 94 participants went through a semi-structured interview, and an oral examination. Diagnosis of oral cGVHD was based on the "National Institutes of Health (NIH) cGVHD diagnosis and staging consensus criteria" from 2014. RESULTS: Mean age at transplantation was 17.5 years (range 0.4-29.9 years), and mean time since transplantation was 16.7 years (range 6-26 years). Oral cGVHD was diagnosed in 26 (28%) of 94 LTSs. Of which 20 (21.5%) showed lichen planus-like (LPL) changes, and additionally six (6.5%) also fulfilled the diagnostic criteria of oral cGVHD since they had one or more distinctive signs and symptoms of oral cGVHD combined with definite cGVHD in another organ. No LTSs reported oral cGVHD (NIH) grade 3. There was a significant association between cGVHD in the oral cavity and cGVHD in another organ (77% vs 29%, p < 0.001). Out of 72 LTSs, who answered the questions regarding taste disturbances, 16 (22%) reported dysgeusia. No LTSs developed secondary malignancies in the oral cavity during follow-up time. CONCLUSION: Oral long-term effects, such as oral cGVHD, may persist for many years after allo-HCT without TBI-conditioning in patients treated at a young age.

Late-Onset, Noninfectious Pulmonary Complications following Allogeneic Hematopoietic Stem Cell Transplantation: A Nationwide Cohort Study of Long-Term Survivors.

BACKGROUND: Survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk for pulmonary adverse events. Data on late-onset noninfectious pulmonary complications in long-term adult survivors of allo-HSCT are limited and incomplete. OBJECTIVES: This study aimed (1) to determine occurrence and degree of pulmonary sequelae in adult survivors of allo-HSCT and (2) to identify associations between pulmonary function, high-resolution CT (HRCT), and clinical characteristics. METHOD: In a nationwide, single-center cross-sectional study, 103 survivors (aged median [range] 35 [17-58] years, 53% females) were examined 17 (6-32) years after allo-HSCT and compared with healthy controls (n = 105). Methods included pulmonary function tests and HRCT. RESULTS: Chronic graft-versus-host disease was diagnosed in 33% of survivors, including 12% with bronchiolitis obliterans syndrome (BOS). Mean lung volumes (TLC, FVC, and FEV1) and gas diffusing capacity were >80% of predicted for the survivors as a group, but significantly lower than in healthy controls. Pathological HRCT findings were detected in 48% of the survivors (71% airways disease, 35% interstitial lung disease, and 24% apical subpleural interstitial thickening). Air trapping (%) on HRCT correlated with % predicted FEV1, p < 0.001. In a multiple logistic regression model, both BOS and pathological findings on HRCT were associated with chemotherapy prior to allo-HSCT, p < 0.05. CONCLUSIONS: Long-term allo-HSCT survivors had significantly lower pulmonary function than age- and gender-matched healthy controls and nearly half had pathological findings on HRCT. Longitudinal data will determine if pulmonary sequelae will remain stable or progress. We recommend lifelong monitoring of pulmonary function in allo-HSCT survivors. HRCT provides additional information, but is not suited for surveillance.

Determinants of cardiorespiratory fitness in very long-term survivors of allogeneic hematopoietic stem cell transplantation: a national cohort study.

PURPOSE: Survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk for cardiopulmonary adverse events. Data on long-term effects on cardiorespiratory fitness are limited. To address the gap in knowledge, we aimed to determine peak oxygen uptake (V̇O2peak) and identify associations between cardiorespiratory fitness and clinical characteristics, self-reported physical activity, cardiac, and pulmonary function. METHODS: In a nationwide, single-center cross-sectional study, 90 survivors [aged median (range) 35 (17-54) years, 56% females] were examined, 17 (6-26) years after allo-HSCT. Myeloablative conditioning comprised busulfan/cyclophosphamide or cyclophosphamide only. Methods included pulmonary function tests, echocardiography, and cardiopulmonary exercise test. RESULTS: Chronic graft-versus-host disease (cGVHD) was found in 31% of the subjects, of whom 40% had bronchiolitis obliterans syndrome (BOS). Seventy-one percent of the survivors did not meet WHO recommendations for physical activity and 42% were overweight. Reduced gas diffusion (DLCO) and systolic ventricular dysfunction (LVEF) were found in 44% and 31%, respectively. For the group, mean (95% CI), V̇O2peak was 36.4 (34.7-38.0) mL/min/kg [89 (85-93)% of predicted]. V̇O2peak was low at 43%. Cardiopulmonary factors and deconditioning were equally common limitations for exercise. In a multiple linear regression model, low V̇O2peak was associated with low DLCO, low LVEF, BOS, overweight, and inactivity. CONCLUSION: Half of the survivors had reduced cardiorespiratory fitness median 17 years after allo-HSCT. Cardiopulmonary factors and deconditioning were equally common limitations to exercise. We encourage long-term cardiopulmonary monitoring of allo-HSCT survivors and targeted advice on modifiable lifestyle factors.

Glutathione Transferase Gene Variants Influence Busulfan Pharmacokinetics and Outcome After Myeloablative Conditioning.

BACKGROUND: Busulfan (Bu) and cyclophosphamide (Cy) are frequently included in conditioning regimens before hematopoietic stem cell transplantation (HSCT). Both drugs are detoxified by glutathione transferases (GST), and GST gene variants may explain some of the interindividual variability in pharmacokinetics and drug toxicity. METHODS: The study investigated adult patients (n = 114) receiving oral Bu pre-HSCT. Bu doses were adjusted to obtain an average steady-state concentration (Css) of 900 mcg/L. RESULTS: Median first dose Bu Css was 1000 mcg/L (600-1780 mcg/L). Patients carrying 1 and 2 GSTA1*B (rs3957357) alleles demonstrated median 12% and 16% higher Bu Css (P ≤ 0.05). Bu exposure (average Css; odds ratio = 1.009, 95% confidence interval = 1.002-1.017, P = 0.013) and GSTM1 gene copy number (odds ratio = 17.1, 95% confidence interval = 1.46-201, P = 0.024) were significant predictors of mortality ≤30 days. The mortality was 25% versus 2% among carriers of 2 versus no GSTM1 copies (P = 0.021). Mortality ≤3 months was associated with higher first dose Bu exposure (1090 versus 980 mcg/L, P = 0.021). GSTM1 expression and high Bu exposure may increase Cy toxicity by reducing intracellular glutathione. CONCLUSIONS: GST genotyping before HSCT may allow better prediction of Bu pharmacokinetics and drug toxicity, and thereby improve outcome after BuCy conditioning.

[Allogeneic stem-cell transplantation in adults 1985-2012: results and development]. / Allogen stamcelletransplantasjon hos voksne 1985-2012.

BACKGROUND: Allogeneic stem cell transplantation (ASCT) has been a treatment option for patients with serious diseases of the blood and haematopoietic organs in Norway since 1985. Such treatment is potentially curative for selected patients who have a relatively short predicted survival with other treatment modalities. This article summarises the experience and results from ASCT at Oslo University Hospital Rikshospitalet. MATERIAL AND METHOD: The study included all of the 734 adult patients who had undergone allogeneic stem cell transplantation at the Department of Haematology, Rikshospitalet, later Oslo University Hospital Rikshospitalet, from November 1985 to October 2012. RESULTS: At the time of analysis, altogether 384 patients were alive, and the five and ten-year survival rates were 54% and 48% respectively. The median follow-up time was six years. A total of 339 patients (46%) had developed acute graft-versus-host disease (GvHD), and 250 (73%) of these had GvHD ≥ grade II. Altogether 280 out of 602 patients who lived ≥ 100 days after the transplantation (46.5%) developed chronic GvHD. The most frequent causes of death included recurrence of the initial disease in 116 patients (33.1 %), multi organ failure after transplantation in 88 patients (25.4%), infections in 54 patients (16%) and GvHD in 33 patients (9.4%). INTERPRETATION: ASCT is a treatment option with a curative potential for patients with serious haematological diseases when other forms of treatment provide few prospects for recovery. The total survival rate in our study is in accordance with international results for the same time period, and the indications have consistently been in line with what is accepted internationally.

Syngeneic transplantation in aplastic anemia: pre-transplant conditioning and peripheral blood are associated with improved engraftment: an observational study on behalf of the Severe Aplastic Anemia and Pediatric Diseases Working Parties of the European Group for Blood and Marrow Transplantation.

Aplastic anemia is usually treated with immunosuppression or allogeneic transplant, depending on patient and disease characteristics. Syngeneic transplant offers a rare treatment opportunity with minimal transplant-related mortality, and offers an insight into disease mechanisms. We present here a retrospective analysis of all syngeneic transplants for aplastic anemia reported to the European Group for Blood and Marrow Transplantation. Between 1976 and 2009, 88 patients received 113 transplants. Most transplants (n=85) were preceded by a conditioning regimen, 22 of these including anti-thymocyte globulin. About half of transplants with data available (39 of 86) were followed by posttransplant immunosuppression. Graft source was bone marrow in the majority of cases (n=77). Transplant practice changed over time with more transplants with conditioning and anti-thymocyte globulin as well as peripheral blood stem cells performed in later years. Ten year overall survival was 93% with 5 transplant-related deaths. Graft failure occurred in 32% of transplants. Risk of graft failure was significantly increased in transplants without conditioning, and with bone marrow as graft source. Lack of posttransplant immunosuppression also showed a trend towards increased risk of graft failure, while anti-thymocyte globulin did not have an influence. In summary, syngeneic transplant is associated with a significant risk of graft failure when no conditioning is given, but has an excellent long-term outcome. Furthermore, our comparatively large series enables us to recommend the use of pre-transplant conditioning rather than not and possibly to prefer peripheral blood as a stem cell source.

Severe hemolytic transfusion reaction due to anti-A1 following allogeneic stem cell transplantation with minor ABO incompatibility.

Blood components should be compatible both with the recipient and the donor in the ABO incompatible allogeneic stem cell transplantation setting. A patient with blood type A2 received peripheral blood stem cells from a blood type O donor. The patient was in critical condition due to treatment-related toxicity. He had acquired anti-A1 that was unfortunately overlooked. Following transfusion of A1 red blood cells in error, he developed a severe hemolytic transfusion reaction. Anti-A1 is rarely clinically significant. We discuss the role of passenger lymphocytes in development of the anti-A1, and stress the importance of investigating unusual/atypical reactions in blood typing.

Graft-Versus-Host-Disease and Health-Related Quality of Life in Young Long-term Survivors of Cancer and Allogeneic Hematopoietic Stem Cell Transplantation.

Purpose: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an established treatment predominantly for malignancies. Chronic graft-versus-host disease (cGVHD) is the leading long-term complication after allo-HSCT, but knowledge on cGVHD and health-related quality of life (HRQOL) in long-term survivors of allo-HSCT performed in childhood, adolescence, and young adulthood (CAYA) is scarce. Therefore, we aimed to (1) assess prevalence and risk factors of active cGVHD using the 2014 National Institutes of Health-Consensus criteria, (2) investigate associations between cGVHD severity, patient-reported symptom burden, and HRQOL, and (3) compare HRQOL of survivors to population norms. Methods: We conducted a nationwide cross-sectional study in long-term survivors of CAYA allo-HSCT combining clinical examinations and patient-reported outcome measures. Results: We included 103 survivors, 55 (53%) females, median age of 19.6 years [range 0.3-29.9] at HSCT, 16.8 years [6.0-32.0] from HSCT, and 77 (75%) with underlying malignancy. Overall, 32 (31%) survivors were diagnosed with active cGVHD. The risk of active cGVHD was increased with prior acute GVHD and reduced with in vivo T cell depletion. cGVHD severity was associated with increased symptom burden, but not with adverse HRQOL. Compared to Norwegian population norms, allo-HSCT survivors reported significantly lower HRQOL. Conclusion: These results indicate a high prevalence of cGVHD in long-term survivors of CAYA allo-HSCT. Although we did not find an association between cGVHD severity and HRQOL, survivors reported significantly poorer HRQOL compared to population norms. Knowledge on the long-term consequences of cGVHD will be important for optimizing treatment and long-term follow-up care after CAYA allo-HSCT.

A clinical study of cervical dysplasia in long-term survivors of allogeneic stem cell transplantation.

This retrospective study examined the prevalence of and risk factors for cervical dysplasia and genital human papillomavirus (HPV) infection in 89 female recipients of allogeneic stem cell transplantation (allo-SCT) between 1985 and 2005 who survived for more than 5 years after transplantation. All patients underwent regular gynecologic examination and cervical cytological testing. The incidence rates of cervical cytological abnormalities and HPV infection were calculated. Various clinical parameters were evaluated for association with cytological high-grade squamous intraepithelial lesion (HSIL) posttransplantation to identify risk factors for cervical dysplasia. Multivariate analysis with logistic regression was used to identify independent risk factors for cervical dysplasia after adjusting for confounding factors. Sixty-one of the 89 patients (68.5%) had cervical cytological abnormalities of varying grades, including atypical squamous cells of undetermined significance (ASC-US; 31.5%; 28 of 89), low-grade squamous intraepithelial lesion (LSIL; 10.1%; 9 of 89), and HSIL (27%; 24 of 89). HPV status was available for 43 patients, 12 of whom (27.9%) were HPV-positive. Among the 69 patients with normal cytological cervical smear findings pretransplantation, the incidence of cytological HSIL was 23.2% (16 of 69) posttransplantation. After adjusting for confounding factors, only unrelated HLA-matched donor and the presence of vulvovaginal chronic graft-versus-host disease (cGVHD) were independent risk factors for cervical cytology HSIL after transplantation, with the highest risk among patients with vulvovaginal cGVHD (adjusted odds ratio, 31.97). We conclude that long-term survivors of allogeneic stem cell transplantation are at high risk for cervical cytological abnormalities. Vulvovaginal cGVHD and unrelated HLA-matched donor were the only independent risk factors for cervical cytological HSIL in patients with normal cervical cytology before transplantation. Regular surveillance by gynecologic examination, including cervical cytological testing, in these patients allows for early diagnosis and effective management of cervical abnormality and decreases the burden of this potentially fatal, but treatable, condition.

Impaired right ventricular function in long-term survivors of allogeneic haematopoietic stem-cell transplantation.

AIMS: Survivors of allogeneic haematopoietic stem-cell transplantation (allo-HSCT) are at higher risk of cardiovascular disease. We aimed to describe right ventricular (RV) systolic function and risk factors for RV dysfunction in long-term survivors of allo-HSCT performed in their youth. METHODS AND RESULTS: This cohort included 103 survivors (53% female), aged (mean±SD) 17.6±9.5 years at allo-HSCT, with a follow-up time of 17.2±5.5 years. Anthracyclines were used as first-line therapy for 44.7% of the survivors. The RV was evaluated with echocardiography, and found survivors to have reduced RV function in comparison to a group of healthy control subjects: Tricuspid annular plane systolic excursion, (TAPSE, 20.8±3.7 mm vs 24.6±3.8 mm, p<0.001), RV peak systolic velocity (RV-s', 11.2±2.3 cm/s vs 12.3±2.3 cm/s, p=0.001), fractional area change (FAC, 41.0±5.2% vs 42.2±5.1%, p=0.047) and RV free-wall strain (RVFWS, -27.1±4.2% vs -28.5±3.3%, p=0.043). RV systolic dysfunction (RVSD) was diagnosed in 14 (13.6%), and was strongly associated with progressive left ventricular systolic dysfunction (LVSD). High dosages of anthracyclines were associated with greater reductions in RV and LV function. Multivariable linear regressions confirmed global longitudinal strain to be a significant independent predictor for reduced RV function. CONCLUSION: Impaired RV function was found in long-term survivors of allo-HSCT who were treated in their youth. This was associated with progressive left ventricle dysfunction, and pretransplant therapies with anthracyclines. The occurrence of RVSD was less frequent and was milder than coexisting LVSD in this cohort.

Left Ventricular Systolic Function in Long-Term Survivors of Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT), a potentially curative therapy for malignant and nonmalignant diseases, is being increasingly used in younger patients. Although allo-HSCT survivors have an established increased risk of cardiovascular disease, there is limited knowledge of the long-term effects on cardiac function in survivors. OBJECTIVES: The purpose of this study was to describe left ventricular (LV) systolic function in long-term allo-HSCT survivors treated in childhood, adolescence, or early adulthood. METHODS: Our cross-sectional cohort study included 104 patients (56% women), age 18 ± 10 years at time allo-HSCT with 17 ± 6 years of follow-up. Echocardiography included 2-dimensional (2D) and 3-dimensional (3D) analyses and speckle tracking imaging. In total, 55 healthy control subjects with a similar age, sex, and body mass index were used for comparison. Left ventricular systolic dysfunction (LVSD) was defined as reduced 2D left ventricular ejection fraction (LVEF) of <52% in men and <54% in women, and/or a reduced global longitudinal strain (GLS) of ≥-17%. Multivariable linear regression was used to determine independent predictors of 2D-LVEF and GLS. RESULTS: Allo-HSCT survivors had significantly reduced LV systolic function compared with control subjects: 2D-LVEF (55.2 ± 5.8% vs. 59.0 ± 2.9%; p < 0.001), 3D LVEF (54.0 ± 5.1% vs. 57.6 ± 2.7%; p < 0.001), and GLS (-17.5 ± 2.2% vs. -19.8 ± 1.4%; p < 0.001). LVSD was found in 44.2%, of whom 28.3% were symptomatic. Clinical factors independently associated with 2D-LVEF and/or GLS included age, anthracyclines, graft versus host disease (GVHD), heart rate, and hypertension. In the 45% of survivors pre-treated with anthracyclines, the effect of anthracyclines on 2D-LVEF and GLS was dose-dependent. CONCLUSIONS: LVSD is common in long-term survivors of allo-HSCT treated in their youth. Pre-HSCT therapies with anthracyclines, age, heart rate, hypertension, and graft versus host disease are associated with measures of LV function.

[High-dose treatment of systemic AL-amyloidosis with autologous stem cell support]. / Høydosebehandling med autolog stamcellestøtte ved systemisk AL-amyloidose.

BACKGROUND: AL-amyloidosis is a serious disease with a short median survival without treatment. Treatment with high-dose melphalan with autologous stem cell support (HMAS) has a potential to increase survival, but is associated with toxicity and mortality. In this paper we report the Norwegian results retrospectively. MATERIAL AND METHODS: We used questionnaires and had personal contact with a local physician from each hospital with HMAS experience. Diagnosis and treatment were evaluated according to the guidelines at the time of treatment, and the results were compared to internationally published reports. RESULTS: Stem cell harvesting was attempted in 18 patients from 1997 to 2006. 15 of these received HMAS treatment. Treatment-related mortality was 20%, and 5 of 11 (45%) had an organ response. Median survival was not reached within the 55-month median observation time. The course of the disease was more complicated when known risk factors for HMAS treatment were present, such as reduced kidney function, advanced heart involvement, reduced performance status, and multiorgan disease. Three of 18 patients were not diagnosed according to relevant guidelines. In seven of 12 patients the response to treatment was not evaluated adequately with respect to haematology. INTERPRETATION: AL-amyloidosis is a difficult diagnosis and the condition is probably under-diagnosed in Norway. The results of HMAS treatment in Norway are comparable with those in published reports from centres abroad. The follow-up of patients should be improved.

[Allogeneic stem cell transplantation in adults with acute lymphoblastic leukaemia]. / Allogen stamcelletransplantasjon hos voksne med akutt lymfoblastisk leukemi.

BACKGROUND: The success rate for chemotherapy of adults with acute lymphoblastic leukaemia in Norway compares favourably with that in international reports, but improvements are still needed. Allogeneic stem cell transplantation is an option for patients up to 60 years and may contribute to improving the outcome for these patients. MATERIAL AND METHODS: Allogen stem cell transplantation was performed in 61 high-risk patients (38 men and 23 women) with acute lymphoblastic leukaemia at Rikshospitalet between 1985 and 2005. 19 patients were transplanted in first remission and 42 at a later stage of the disease. RESULTS: At the end of 2006, 26 patients (43%) were alive; 21 (35%) in complete remission and 5 with relapse. Median survival time was 1.5 years. Relapse was the most important cause of treatment failure (38%), but transplantation-related mortality (25%) was also a substantial problem. Estimated 5-year actuarial leukemia-free survival was 35 %. INTERPRETATION: Our results are in line with international reports on the results of allogen stem cell transplantation in high-risk acute lymphoblastic leukaemia. This treatment offers cure for patients with an otherwise dismal prognosis. A larger number of patients should be offered such treatment during the first remission than what was the case in the 20-year period this study took place.

Ocular findings and ocular graft-versus-host disease after allogeneic stem cell transplantation without total body irradiation.

Patients treated with allogeneic stem cell transplantation (allo-SCT) often develop ocular complications. To investigate the ocular findings in young long-term survivors after allo-SCT without TBI, we examined 96 patients more than 5 years after transplantation. All patients were under 30 years of age at transplantation. The mean follow-up time was 16.8 years (range 6.0-26.1 years). The study was a part of the Norwegian Allo Survivorship Study investigating health impairments in young survivors after allo-SCT. Ophthalmological examination included visual acuity, tear break-up time, corneal fluorescein staining, Schirmer I test, tear film osmolarity, biomicroscopy and dilated ophthalmoscopy. In patients with known systemic chronic GVHD (cGVHD), ocular GVHD (oGVHD) diagnosed by clinical examination was compared with diagnosis using National Institutes of Health (NIH) or International Chronic Ocular Graft-vs-Host-Disease (ICCGVHD) Consensus Group criteria. We diagnosed dry eye disease (DED) in 52 patients (54%), cataract in 3 patients (3%) and retinopathy in 1 patient (1%). Systemic cGVHD was a risk factor for DED (OR 4.40, CI 1.33-14.56, p = 0.02). Comparison of diagnostic criteria suggests that the more stringent ICCGVHD criteria can better differentiate DED from oGVHD after allo-SCT as compared with the NIH criteria.

Effects of individualized nutrition after allogeneic hematopoietic stem cell transplantation following myeloablative conditioning; a randomized controlled trial.

BACKGROUND & AIMS: Reduced quality of life (QoL) is prevalent after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this randomized trial we examined the effect of individualized nutritional support during hospitalization for allo-HSCT. Primary outcome was change in global QoL three months post-HSCT with oral mucositis (OM) and acute graft-versus-host disease (aGVHD) as main secondary outcomes. METHODS: Whereas the intervention group received recommended minimum daily intakes of 126 kJ/kg and 1.5-2.0 g protein/kg as food, supplements, enteral or parenteral nutrition, the controls received routine feeding. QoL was self-reported using the EORTC QLQ-C30 questionnaire. RESULTS: Between August, 2010 and February, 2016, we randomized 59 and 60 patients to intervention and control, respectively; 40 and 48 being eligible for analysis of QoL. There was no difference between the two groups in mean global QoL after three months (-3.10, 95% CI -11.90-5.69; P = 0.49). Nor were there any differences in OM grades 3 or 4 (RR (vs grades 0-2), 1.11, 95% CI 0.59-2.11 and 0.95, 95% CI 0.72-1.25, respectively; P = 0.78), or aGVHD grades 3 or 4 (RR (vs grades 0-2) 0.44, 95% CI 0.12-1.60; and 0.65, 95% CI 0.20-2.20, respectively; P = 0.37). CONCLUSION: Individualized nutritional support with recommended energy and protein intakes during hospitalization had no effect on QoL, OM or aGVHD three months after allo-HSCT compared to routine nutrition.

[Non-myeloablative allogeneic stem cell transplantation]. / Allogen stamcelletransplantasjon med redusert forbehandling.

BACKGROUND: Several haematological malignancies can be cured using allogeneic stem cell transplantation (SCT). Maximal tolerable chemoradiotherapy doses are given as part of the conditioning-regimen. This treatment causes substantial toxicity, and the procedure is therefore restricted to patients younger than 60 years without co-morbidity. Non-myeloablative allogeneic SCT, is a treatment modality that can be offered to patients up to 70 years of age and to younger patients with co-morbidity. MATERIAL AND METHODS: 21 patients (17 men and 4 women) with different haematological malignancies, have been treated with non-myeloablative allogeneic SCT in our institution from October 2000 to May 2005. RESULTS: The transplant procedure was relatively non-toxic. Four patients required transfusions and 3 required empirical antibiotic treatment, which is always necessary after myoablavative allogen SCT. A stable donor chimerism was achieved for most of our patients before day 84. 11 patients suffered from acute graft versus host disease (GVHD), 6 with debut of symptoms after day 100. 11 patients developed chronic GVHD. 14 patients are alive and 7 are dead; 2 due to transplant-related complications and 5 due to disease progression. INTERPRETATION: We have shown that non-myeloablative allogeneic SCT is feasible with an acceptable toxicity. Acute and chronic GVHD is still a substantial problem. Prospective studies with adequate controls are warranted to determine the future role of non-myeloablative allogeneic SCT.

Intensive therapy for multiple myeloma in patients younger than 60 years. Long-term results focusing on the effect of the degree of response on survival and relapse pattern after transplantation.

BACKGROUND AND OBJECTIVES: From 1994 to 1997 we conducted a population-based, prospective study on intensive therapy in newly diagnosed symptomatic myeloma patients younger than 60 years, comparing their survival to that of a conventionally treated historic population. Long-term results are presented, including the impact of the degree of response on survival and relapse pattern after transplantation. DESIGN AND METHODS: The prospective population was formed of 397 patients and the historic population of 313 patients. Both populations were calculated to comprise more than 75% of the expected number of new cases. RESULTS: After a median follow-up of 7 years survival was longer in the prospective population than in the historic one (median 60 versus 39 months; p=0.0002). When comparing only patients eligible for intensive therapy the median survival was 63 versus 44 months (p<0.0001). Attaining a complete response was associated with prolonged event-free survival but not overall survival. The pattern of relapse after transplantation was heterogeneous but could be divided into four major groups; insidious, classical, plasmacytoma form and transformed disease. The median survival after relapse was 29 months. The relapse pattern and time to relapse predicted outcome. Patients relapsing with an insidious or classical form of disease with skeletal events only, or after a long lasting first response were likely to respond well to conventional salvage therapy. In contrast, relapse with multiple symptoms, transformed disease or a short duration of first response implied bad prognosis. INTERPRETATION AND CONCLUSIONS: The relapse pattern after autologous transplantation is heterogeneous and response to salvage therapy is variable. The degree of response and event-free survival after transplantation are not reliable surrogate markers for survival.

A phase I/II study of the MDR modulator Valspodar (PSC 833) combined with daunorubicin and cytarabine in patients with relapsed and primary refractory acute myeloid leukemia.

The cyclosporine analog Valspodar (PSC 833, Novartis Pharma) is a strong inhibitor of the mdr1 gene product p-glycoprotein (pgp). A phase I/II study was conducted in order to evaluate if addition of Valspodar to treatment with daunorubicin and cytarabine, given to patients with primary refractory or relapsed acute myeloid leukemia, could increase the complete remission rate.Fifty-three patients were treated in cohorts of three to six patients. Twelve patients reached a complete remission in bone marrow, five of whom also normalized their peripheral blood values. Three patients experienced treatment-related deaths from pneumonia, liver failure and cerebral hemorrhage, respectively. It is concluded that Valspodar 10 mg/kg per 24 h in combination with daunorubicin 45 mg/m(2) for 3 days and cytarabine 1 g/m(2) twice daily for 4 days is tolerable in this heavily pre-treated group of patients. Due to the moderate treatment results, the phase II part of the study was ended prematurely. The modulation of only pgp did not give an obvious improvement of the treatment results in this group of patients.

[Clinical use of haematopoietic stem cells from cord blood]. / Klinisk bruk av hematopoetiske stamceller fra navlestrengsblod.

A group of experts appointed by the Norwegian Centre for Health Technology Assessment (SMM) has undertaken a systematic review of available literature on the clinical effectiveness of transplanting haematopoietic stem cells from cord blood. A total of 17 studies form the documentary basis of the review. Autologous transplants of stem cells from cord blood have not been published. Retrospective studies suggest that the clinical effect of allogeneic cord blood transplants, at least in children, is comparable to transplants with allogeneic stem cells from bone marrow or peripheral blood cells. This review demonstrates the need for prospective studies comparing transplantations of cord blood with bone marrow or peripheral blood stem cells.