Patients' perception of health-related quality of life during the first year after autologous and allogeneic stem cell transplantation.

Little attention has been paid to examine health-related quality of life (HRQoL) the first year post-transplant, despite that this period is crucial for returning to normal life and functioning and to prevent delayed psychosocial adjustment. The purpose of the present study was to describe HRQoL after autologous versus allogeneic stem cell transplantations during the first year post-transplant. The allogeneic group was further divided into two groups: allogeneic stem cell transplantation after reduced intensive conditioning and allogeneic stem cell transplantation after myeloablative conditioning. All together 202 patients were enrolled in the study. HRQoL was assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the treatment-specific module High-Dose Chemotherapy (HDC-19). The questionnaires were filled out at six occasions (from inclusion to 12 months after transplantation). The reduced intensive conditioning group seemed to recover in the same way as the autologous group and these two groups were closer in their scoring compared with the myeloablative conditioning group. One month after the transplantation there were no significant differences in change scores between the autologous and reduced intensive conditioning group, and 1 year after the transplantation levels of symptoms and functioning were back to baseline or better. The myeloablative conditioning group, who perceived more symptoms and lower levels of functioning during the whole period, was still impaired in 10 out of 29 scales 1 year after the transplantation and no significant improvements compared with baseline were observed for this group.

Attitude towards remission induction for elderly patients with acute myeloid leukemia influences survival.

Combination chemotherapy may induce remission from acute myeloid leukemia (AML), but validated criteria for treatment of elderly are lacking. The remission intention (RI) rate for elderly patients, as reported to the Swedish Leukemia Registry, was known to be different when comparing the six health care regions, but the consequences of different management are unknown. The Leukemia Registry, containing 1672 AML patients diagnosed between 1997 and 2001, with 98% coverage and a median follow-up of 4 years, was completed with data from the compulsory cancer and population registries. Among 506 treated and untreated patients aged 70-79 years with AML (non-APL), there was a direct correlation between the RI rate in each health region (range 36-76%) and the two-year overall survival, with no censored observations (6-21%) (chi-squared for trend=11.3, P<0.001; r2=0.86, P<0.02, nonparametric). A 1-month landmark analysis showed significantly better survival in regions with higher RI rates (P=0.003). Differences could not be explained by demographics, and was found in both de novo and secondary leukemias. The 5-year survival of the overall population aged 70-79 years was similar between the regions. Survival of 70-79-year-old AML patients is better in regions where more elderly patients are judged eligible for remission induction.

Autologous and allogeneic stem cell transplantation in adult ALL: the Swedish Adult ALL Group experience.

Adult patients with acute lymphoblastic leukaemia (ALL) have been treated according to national protocols in Sweden since 1986. Stem cell transplantation (SCT) has been recommended in first remission for patients with risk factors for relapse, and for standard risk patients only after relapse. In this retrospective study, the results of autologous and allogeneic SCT in these populations were evaluated. In total, 187 patients with a median age of 34 years (17-66 years) underwent SCT. The 5-year disease-free survival (DFS), for all patients, was 26% (Confidence intervals (CI) 20-32%). The 5-year DFS was higher for patients transplanted in first remission 32% (CI 24-40%) compared to 14% (CI 5-23%; P<0.0001) in patients transplanted beyond first remission. No significant differences in DFS (P=0.06) were determined between autologous, related donor and unrelated donor SCT in the whole cohort. A lower relapse rate was counterbalanced by higher treatment-related mortality in patients undergoing allogeneic SCT. In Philadelphia-positive ALL, allogeneic SCT was superior to autologous SCT, with a 5-year DFS of 30% (CI 12-47%) vs 0% (P=0.04). Limited chronic graft-versus-host-disease (GVHD) was associated with an improved DFS of 53% (CI 38-69%) compared to no chronic GVHD of 22% (CI 10-36%; P=0.0008), indicating a clinically important graft-versus-leukaemia effect.

Management and prognostic features of intracerebral hemorrhage during anticoagulant therapy: a Swedish multicenter study.

BACKGROUND AND PURPOSE: Patients treated with oral anticoagulants (ACs) have an increased risk of intracerebral hemorrhage (ICH), which is more often fatal than spontaneous ICH. Options to reverse the AC effect include intravenous administration of vitamin K, plasma, and coagulation factor concentrate. However, the optimal management of AC-related ICH has not been determined in any randomized trial. In this study, the present management of AC-related ICH was surveyed, and determinants of survival were assessed. METHODS: We retrospectively reviewed the medical records of all AC-related ICHs at 10 Swedish hospitals during a 4-year period, 1993 to 1996. Survival status after the ICH was determined from the Swedish National population register. RESULTS: We identified 151 patients with AC-related ICH. Death rates were 53.6% at 30 days, 63.6% at 6 months, and 77.5% at follow-up (mean 3.5 years). The case fatality ratio at 30 days was 96% among patients unconscious on admission (n=27), 80% among patients who became unconscious before active treatment was started (n=15), 55% among patients in whom no special action was taken except withdrawal of AC treatment (n=42), and 28% among patients given active anti-coumarin treatment while they were still conscious (n=64). The case fatality ratio at 30 days was 11% in the group treated with plasma (n=18), 30% in the group treated with vitamin K (n=23), and 39% in the group treated with coagulation factor concentrate (n=23). Within the first 24 to 48 hours after admission, 47% of the patients deteriorated. Choice of therapy to reverse the AC effect differed substantially between the hospitals (P<0.0001), as did the time interval from symptom onset to start of treatment. Multiple logistic regression analysis showed only 2 factors (intraventricular extension of bleeding and ICH volume) that were independently related to case fatality at both 30 days and 6 months. The results were similar when the analysis was restricted to patients who were conscious on admission. CONCLUSIONS: In AC-related ICH, a progressive neurological deterioration during the first 24 to 48 hours after admission is frequent, and the mortality is high. Choice of therapy to reverse the AC effect differed considerably between the hospitals. There was no evidence that any treatment strategy was superior to the others. A randomized controlled trial is needed to determine the best choice of treatment.

Naturally occurring IgG autoantibodies to platelet cytoskeleton tropomyosin.

We have observed that naturally occurring serum antibodies generated a 30 Kd band in a platelet immunoblot assay. The target protein had the same molecular weight (30 Kd) under nonreduced and reduced electrophoretic conditions, and could be immunoblotted from either autologous or homologous platelet lysates. Also, the 30 Kd reactive autoantibodies could be totally adsorbed by platelet cytoskeletons. From these data one likely candidate for the autoantibody target was the intracellular platelet protein tropomyosin. Indeed, a commercially available monoclonal anti-tropomyosin antibody reacted with proteins comigrating with this 30 Kd band; affinity purified human platelet tropomyosin was bound by the antibodies that recognized the 30 Kd protein. This body of evidence conclusively demonstrated that naturally occurring serum autoantibodies reacted with the platelet cyto-skeleton protein-tropomyosin. These tropomyosin specific antibodies were found in roughly the same percentage of sera from patients with chronic idiopathic thrombocytopenic purpura (ITP) as from normal individuals.

Pharmacokinetics and pharmacodynamics of melagatran, a novel synthetic LMW thrombin inhibitor, in patients with acute DVT.

Forty-eight patients with acute proximal deep vein thrombosis (DVT) were randomised to intravenous infusions for 4 to 6 days with melagatran, a novel synthetic low molecular weight thrombin inhibitor, or unfractionated heparin adjusted by the activated partial thromboplastin time (APTT). The aim of the study was to investigate the pharmacokinetics, pharmacodynamics and the safety of melagatran therapy at three different doses. Steady-state plasma concentrations were rapidly achieved and maintained throughout the infusion period. The mean plasma concentrations in the low, medium and high dose groups were 0.17, 0.31 and 0.53 micromol/l, respectively. The prolongation of APTT was stable during the melagatran infusions and correlated to the plasma concentration. Phlebographically verified regression of thrombus size measured as decrease in Marder score was seen after 4 to 6 days in 8 of 12 patients, 6 of 12 patients and 5 of 11 patients in the low, medium and high dose groups of melagatran and in 5 of the heparin-treated patients. In the low dose group with melagatran, thrombus extension was seen in one patient. At the dose levels studied, melagatran was well tolerated with no clinically significant bleeding problems, suggesting that melagatran could safely be given to patients suffering from DVT.

Favorable outcome with STI571 (imatinib mesylate) and allogeneic stem cell transplantation in a case of Ph+ chemorefractory acute lymphocytic leukaemia.

We present a patient with a Philadelphia chromosome positive (Ph+) acute lymphocytic leukaemia (ALL) refractory to standard induction chemotherapy. Treatment with the ABL-specific tyrosine kinase inhibitor STI571 (Glivec, Gleevec, imatinib mesylate) resulted in a complete haematologic and cytogenetic remission. Allogeneic stem cell transplantation from an unrelated donor could be undertaken while the patient was in STI571-induced complete remission from the leukaemia. At present, the patient has a 15-month post-transplantation follow-up and is in stable molecular remission as evaluated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) for the BCR/ABL fusion gene transcript. Our case demonstrates that STI571 can act as a bridge to potentially curative allogeneic stem cell transplant in otherwise poor prognosis Ph+ ALL.

More efficient mobilisation of peripheral blood stem cells with HiDAC+AMSA+G-CSF than with mini-ICE+G-CSF in patients with AML.

We have compared the efficacy of two PBSC mobilisation regimens, mini-ICE+filgrastim (second consolidation) and HiDAC+AMSA+filgrastim (third consolidation), in two consecutive cohorts of patients with AML CR1 receiving treatment according to a joint protocol. Group A: 18 patients, aged 41 (21-65) years, were mobilised with mini-ICE (idarubicin 8 mg/m(2)+cytarabine 800 mg/m(2)+etoposide 150 mg/m(2) days 1-3) followed by filgrastim 300-480 microg once daily s.c. from day 11 after start of chemotherapy. Only four patients reached >5 CD34+ cells/microl blood (B-CD34+) and were able to undergo leukaphereses. Two out of 18 (11%) reached the defined target of >/=2.0 x 10(6) CD34+ cells/kg after 1-3 leukaphereses. Group B: 20 patients, aged 50 (29-67) years, received HiDAC+AMSA (cytarabine 3 g/m(2) b.i.d. days 1, 3, 5+amsacrine 150 mg/m(2) q.d. days 2, 4) followed by filgrastim at a similar dose starting on day 7. A total of 18 patients reached B-CD34+ >5/microl and underwent PBSC harvesting, starting on day 23 (14-29) and yielding 4.0 (0.9-21) x 10(6) CD34+ cells/kg. Of 20 patients, 17 (85%) reached the defined target of >/=2.0 x 10(6) CD34+ cells/kg after 1-3 leukaphereses. We conclude that HiDAC+AMSA+G-CSF - in contrast to mini-ICE+G-CSF - is an efficient regimen for mobilising PBSC in patients with AML CR1.

The relation between plasma thrombopoietin and erythropoietin concentrations in polycythaemia vera and essential thrombocythaemia.

Plasma thrombopoietin (TPO) was measured, by immunoenzymometric assay, in 39 patients with polycythaemia vera (PV), 33 patients with essential thrombocythaemia (ET) and 10 healthy volunteers. The mean TPO concentration was significantly higher in ET patients than in PV patients (p=0.04) and normals (p<0.001). The 6 untreated ET patients had a significantly lower mean TPO concentration compared to the 27 ET patients who were on myelosuppressive regimens (p=0.01). The mean plasma TPO for the 5 PV patients treated with phlebotomy only did not differ significantly from the corresponding mean for the 34 PV patients treated with myelosuppressive agents. Concomitantly, plasma EPO was measured in 25 of the PV patients and in 30 of the ET patients by an immunoradiometric assay with normal reference interval in adults 3.7-16 IU/L. In the 14 PV patients with EPO <3.7 IU/L mean plasma TPO did not differ significantly from the mean for the 11 PV patients with EPO >or=3.7 IU/L; neither of these two groups had plasma TPO concentrations significantly different from the mean for the control subjects. The 7 ET patients with subnormal plasma EPO had significantly lower mean plasma TPO compared to the ET patients with normal and high plasma EPO concentrations (p=0.03 and p=0.02, respectively). Also, the 16 ET patients with normal plasma EPO had significantly lower plasma TPO compared to the 8 patients with high plasma EPO (p=0.04). The mean plasma TPO for each of these three groups of ET patients was significantly higher than the corresponding mean for the controls (p<0.001 for each group). The results of the present study indicate that a relationship between plasma EPO and TPO concentrations may exist and that myelosuppressive treatment affects the TPO concentration in ET but not in PV patients.

Treatment of Deep Vein Thrombosis with Low Molecular Weight Heparin at Patient's Home.

We have applied the low molecular weight heparin dalteparin as once-daily subcutaneous injections to the treatment of deep vein thrombosis (DVT) on an outpatient basis since 1994. Until today, 377 consecutive patients with DVT below the inguinal ligament have been treated at home with dalteparin. The patients administered the injections themselves or with the help of either a relative or a primary nurse. Here we report the outcome of the 212 patients treated during 1994-1995, which has been followed for 2 years after the start of treatment. At the 2-year follow-up only 13 patients (6.6%) had suffered a recurrent DVT and of these none were on continuous dicumarol treatment. No cases of major bleedings were seen. This new therapeutic approach for the treatment of DVT is safe, most of the patients are able to treat themselves, and the patients are satisfied with the home treatment model.

Platelet proteins as autoantibody targets in idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura (ITP), caused by autoantibodies directed against certain platelet antigens, is the most common entity of the immune thrombocytopenias. ITP is an acquired disorder and can affect both children and adults. However, the clinical syndromes of ITP are distinct between children and adults. Childhood (acute) ITP characteristically is acute in onset, occurs within 1-2 weeks of an infection, usually of viral origin, resolves spontaneously within 6 months. Adult (chronic) ITP has an insidious onset and rarely resolves spontaneously. Over the last decade considerable new information has accumulated as to the pathophysiological mechanisms of immune thrombocytopenias. In addition, most of the knowledge on this disorder has been obtained from studies of adult patients with chronic ITP. The present work gives an updated overview of the platelet autoantigens and the molecular immunological reactions in ITP.

Incidence and prognostic significance of karyotypic subgroups in older patients with acute myeloid leukemia: the Swedish population-based experience.

The Swedish population-based acute myeloid leukemia registry contains data from 3251 patients (excluding acute promyelocytic leukemia) diagnosed between 1997 and 2006. Informative cytogenetic data from 1893 patients were retrospectively added, including 1054 patients aged between 60 and 79 years. Clonal abnormalities were found in 57% of the informative karyotypes. Karyotypic patterns differed by age: t(8;21), inv(16) and t(11q23) were more common in younger patients, whereas loss of 5q, 7q and 17p, monosomal karyotype (MK) and complex karyotypes were more common in older patients. Loss of 5q, 7q and 17p often occurred together within MK. Patients with 5 chromosome abnormalities had worse overall survival than those with fewer abnormalities or normal karyotype in all age groups. Loss of 5q, 7q and/or 17p had, in contrast to MK, a further negative impact on survival. Multivariable Cox regression analyses on risk factors in patients <80 years with cytogenetic abnormalities and intensive treatment revealed that age and performance status had the most significant impact on survival (both P<0.001), followed by sex (P=0.0135) and a karyotype including -7/del(7q) (P=0.048).

Prerequisites required for the provision and use of web-based communication for psychosocial support in haematologic care.

PURPOSE: The purpose of this study was to describe the prerequisites required for the provision and use of web-based communication for psychosocial support within a haematology clinic, from a patient and family perspective. METHOD: A qualitative design using content analysis was used. A strategically selected sample of patients (n = 11) and family members (n = 6) were offered access to a web-based communication capability with a nurse. After four months, individual interviews were conducted with all participants, in order to identify necessary prerequisites. RESULTS: Preferences and characteristics of the individual patient or family member are crucial as to whether web-based communication for support is perceived as useful. To feel comfortable with writing and to self-identify the need for support are fundamental in getting motivated to use web-based communication. An effective organization around psychosocial support in general is another prerequisite. Goals and responsibilities must be clearly defined for patients and family members to understand their rights and enable the transformation of opportunities into practice. The use of web-based communication must also be a convenient and naturally incorporated part of both individual and organizational use of the web in general. CONCLUSIONS: Prerequisites of taking into account caretakers' different preferences and needs, providing highly structured psychosocial support activities and providing a congruent range of web services, are necessary for successful provision and use of web-based communication for psychosocial support.

Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry.

Our knowledge about acute promyelocytic leukemia (APL) patients is mainly based on data from clinical trials, whereas population-based information is scarce. We studied APL patients diagnosed between 1997 and 2006 in the population-based Swedish Adult Acute Leukemia Registry. Of a total of 3897 acute leukemia cases, 3205 (82%) had non-APL acute myeloid leukemia (AML) and 105 (2.7%) had APL. The incidence of APL was 0.145 per 100,000 inhabitants per year. The median age at the time of diagnosis was 54 years; 62% were female and 38% male. Among younger APL patients, female sex predominated (89% of patients <40 years). Of the 105 APL patients, 30 (29%) died within 30 days (that is, early death (ED)) (median 4 days) and 28 (26%) within 14 days from diagnosis. In all, 41% of the EDs were due to hemorrhage; 35% of ED patients never received all-trans-retinoic acid treatment. ED rates increased with age but more clearly with poor performance status. ED was also associated with high white blood cells, lactate dehydrogenase, creatinine, C-reactive protein and low platelet count. Of non-ED patients, 97% achieved complete remission of which 16% subsequently relapsed. In total, 62% are still alive at 6.4 years median follow-up. We conclude that ED rates remain very high in an unselected APL population.

Gut protection by palifermin during autologous haematopoietic SCT.

Conditioning therapy in connection with haematopoietic SCT (HSCT) induces a disruption of the intestinal barrier function facilitating the permeation of bacteria and endotoxin through the bowel wall with subsequent increased risk of septicaemia and a worsening of GVHD in the allogeneic setting. Palifermin (recombinant human keratinocyte growth factor) reduces the severity of oral mucositis with HSCT. The present trial investigates its effect on intestinal barrier function. Seventeen lymphoma patients undergoing autologous HSCT received palifermin. Intestinal permeability was assessed before the conditioning therapy and on days +4 and +14. Clinical oral and gastrointestinal toxicity was prospectively assessed in parallel. A comparison was made with matched historical study patients (n=21). Patients treated with palifermin had a significantly better preserved intestinal barrier function (P=0.01 on day +4) and were in less need of total parenteral nutrition (P=0.005) as compared with controls. No significant reduction of clinical gastrointestinal or oral toxicity was observed. The intestinal barrier function, normally disrupted by the conditioning therapy, is preserved by palifermin. Whether intestinal barrier preservation protects from invasive infections, and in the allogeneic setting diminishes GVHD severity, remains to be investigated in randomized controlled trials.

Optimization of the detection of microbes in blood from immunocompromised patients with haematological malignancies.

The present study aimed to improve the rate of detection of blood-borne microbes by using PCRs with pan-bacterial and Candida specificity. Seventeen per cent of the blood samples (n=178) collected from 107 febrile patients with haematological malignancies were positive using standard culture (BacT/Alert system). Candida PCR was positive in 12 patients, only one of whom scored culture-positive. Bacterial PCR using fresh blood samples was often negative, but the detection rate increased when the blood was pre-incubated for 2 days. These data indicate that PCR assays might be a complement for the detection of blood-borne opportunists in immunocompromised haematology patients.

Health related quality of life in stem cell transplantation: clinical and psychometric validation of the questionnaire module, High Dose Chemotherapy (HDC-19).

The objective of this study was to assess the psychometric properties of the HDC-19, a module questionnaire for assessing symptoms and problems of patients undergoing stem cell transplantation (SCT) following high-dose chemotherapy (HDC). It consists of 19 questions and was developed for use in conjunction with EORTC QLQ-C30. Psychometric evaluations were performed according to guidelines recommended by the EORTC. The principal component analyses suggested that nine of the HDC-19 items could be reduced to four components (sexual functioning, future health perspectives, skin irritations and joint/muscle pain). Multitrait scaling analysis showed that most item-scale correlation coefficients met the standards of convergent (>0.40) and discriminant validity. Test-retest reliability coefficients between assessments at inclusion and admission were high, indicating that perceived health status remained virtually unchanged during this period. As expected, correlations between admission and one month after transplantation were considerably lower. The internal consistency of the multi-item scales was also satisfactory, (Cronbach's alpha 0.59-0.87). Overall, the known-groups comparisons showed smaller differences between designated groups than expected. As expected, changes in the HDC-19 mirrored changes in QLQ-C30 'global quality of life'. These results lend support to the validity of the HDC-19 as a supplementary questionnaire for assessing specific health-related quality of life (HRQOL) issues relevant for SCT patients.