Lorentz Brinch

A prospective study of health-related quality of life, fatigue, anxiety and depression 3-5 years after stem cell transplantation

Summary:Health-related quality of life (HRQOL), fatigue and psychological distress were prospectively assessed in 248 cancer patients treated with allogeneic (SCT, N=61), or autologous (ASCT, N=69) stem cell transplantation or conventional chemotherapy (CT, N=118) of whom 128 completed the assessments after 3 years. The European Organization for Treatment and Research of Cancer Core Quality of Life Questionnaire and the Hospital Anxiety and Depression Scale were administered nine (SCT/ASCT groups) or seven times (CT group) during the first year. The Fatigue Questionnaire was added at the final assessment. The SCT group displayed greater changes from baseline scores than the ASCT group, with more symptoms in the first months post transplant. A gradual improvement was found in both groups during the following 4–6 months, before stabilizing at baseline levels. Only minor changes were observed after the first year. All groups reported more fatigue than the population values after 3 years (P<0.01). The ASCT group also reported less optimal HRQOL (P<0.01–0.0001). No differences were found in anxiety and depression. Despite a faster recovery during the first months after transplant, the ASCT patients reported poorer functioning and more fatigue compared to the SCT group after 3 years. This suggests a need for a closer follow-up of these patients with special emphasis on functional status and fatigue.

Transplantation of peripheral blood progenitor cells from HLA-identical sibling donors

Transplantation of peripheral blood progenitor cells (PBPCs) has largely replaced autologous bone marrow transplantation. The same might occur in the allogeneic setting if the favourable initial experience with allogeneic PBPCT is confirmed. We analysed all primary transplants utilizing unmodified PBPC from HLA‐identical sibling donors reported to the European Group for Blood and Marrow Transplantation (EBMT) for 1994. 59 patients with a median age of 39 years received myeloablative therapy for acute myelogenous leukaemia (23 patients), acute lymphoblastic leukaemia (13), chronic myelogenous leukaemia (nine), lymphoma (seven), or other diagnoses (seven) mostly of advanced stages followed by transplantation of allogeneic PBPC.

Anterior myocardial infarction with acute percutaneous coronary intervention and intracoronary injection of autologous mononuclear bone marrow cells: safety, clinical outcome, and serial changes in left ventricular function during 12-months' follow-up.

To the Editor: Intracoronary injection of bone marrow cells (BMC) has been introduced for improvement of left ventricular (LV) function after acute myocardial infarction (AMI). In the randomized ASTAMI (Autologous Stem cell Transplantation in Acute Myocardial Infarction) study, BMC treatment did not

Thrombotic thrombocytopenic purpura after allogeneic stem cell transplantation: a survey of the European Group for Blood and Marrow Transplantation (EBMT)

Summary. A survey was carried out among the European Group for Blood and Marrow Transplantation (EBMT) centres to determine the incidence, risk factors, treatment and outcome of thrombotic thrombocytopenic purpura (TTP) following allogeneic haematopoietic stem cell transplantation. TTP was defined as the simultaneous occurrence of red cell fragmentation, laboratory findings of haemolysis, red cell transfusion requirement and de novo or persistant thrombocytopenia caused by consumption, in the absence of disseminated intravascular coagulation. Forty‐five centres reported all patients (n = 406) transplanted between July and December 1996. Twenty‐three patients developed TTP; the risk of developing TTP was 6·7% at 2 years (95% CI: 4·1% to 9·3%). The median time of onset was 44 d (range 13–319) post transplantation. Significant risk factors for the development of TTP were female gender (P = 0·005) and an unrelated donor (P = 0·046). To treat TTP, cyclosporin administration was discontinued in 10 cases, plasma exchanges were performed in five cases and 12 patients received plasma infusions without plasma exchange. TTP resolved in 13 of the 23 patients (57%). The only factor predictive of resolution of TTP was the absence of nephropathy. Seven patients (30%) were alive at follow‐up of 38–45 months from the onset of TTP. Sixteen patients died; the causes were multiple, only three patients had TTP as a central factor. The median time to death was 41 d (range 1–762 d) from the onset of TTP. TTP is a relatively frequent complication of allogeneic stem cell transplantation and it is associated with high mortality, though death is usually caused by multiple factors.

Health-related quality of life in multiple myeloma patients receiving high-dose chemotherapy with autologous blood stem-cell support

In a population-based study, the Nordic Myeloma Study Group found a survival advantage for high-dose melphalan with autologous blood stem-cell support compared to conventional chemotherapy in myeloma patients under 60 yr of age (risk ratio: 1.62; confidence interval [CI] 1.22–2.15; p=0.001). A study of health-related quality of life (HRQoL) was integrated in the trial, using the EORTC QLQ-C30 questionnaire. Of the 274 patients receiving intensive therapy 221 (81%) were compared to 113 (94%) of 120 patients receiving conventional melphalan-prednisone treatment.Prior to treatment, there were no statistically significant differences in any HRQoL score between the two groups. One month after the start of induction chemotherapy, the patients on intensive treatment had more sleep disturbance than the control patients. At 6 mo, corresponding to a mean of 52 d after high-dose melphalan, the patients on intensive treatment had moderately lower scores for global QoL and role and social functioning and there was also a significantly higher score for appetite loss. At 12 and 24 mo, the HRQoL was similar to that of the control patients. At 36 mo, there was a trend toward less fatigue, pain, nausea, and appetite loss in the intensive-treatment group. Thus, the 18 mo of prolonged survival seem to be associated with a good health-related quality of life. Despite the moderate HRQoL reduction associated with the early intensive chemotherapy phase, this treatment modality must be regarded as an important step forward in the care of multiple myeloma.

Impact of age on survival after intensive therapy for multiple myeloma: a population-based study by the Nordic Myeloma Study Group.

The value of intensive therapy, including autologous stem cell transplantation, in newly diagnosed myeloma patients >60 years is not clear. We evaluated the impact of age (<60 years vs. 60–64 years) on survival in a prospective, population‐based setting and compared survival with conventionally treated historic controls. The prospective population comprised 452 patients registered between 1998 and 2000. Of these, 414 received intensive therapy. The historic population, derived from our most recent population‐based study on conventional therapy, comprised 281 patients. Of these, 243 fulfilled our eligibility criteria for intensive therapy. For patients undergoing intensive therapy it was found that two factors, beta‐2‐microglobulin and age <60 years vs. 60–64 years, had independent prognostic impact on survival. However, compared with the historic controls a survival advantage was found both for patients <60 (median 66 months vs. 43 months, P < 0·001) and 60–64 years (median 50 months vs. 27 months; P = 0·001). We conclude that in a population‐based setting higher age adversely influences outcome after intensive therapy. Our results indicate that intensive therapy prolongs survival also at age 60–64 years but with less superiority than in younger patients.

NO PREVENTION OF CYTOMEGALOVIRUS INFECTION BY ANTI-CYTOMEGALOVIRUS HYPERIMMUNE GLOBULIN IN SERONEGATIVE BONE MARROW TRANSPLANT RECIPIENTS

A randomized multicentre study was conducted to evaluate the effect of anti-CMV hyperimmune globulin in the prophylaxis of CMV infections in CMV seronegative allogeneic BMT patients who received a transplant from a seropositive donor or who had received blood products unscreened for CMV during the treatment before BMT. Twenty-eight patients were included in the study. Thirteen were randomized to receive and 15 not to receive intravenous CMV hyperimmune globulin. A dose of 0.4 g/kg of immunoglobulin was given on day −8 and 0.2 g/kg on days −1, +7, +14, +21, +28, +35, +42, +56 and +70 in relation to the day of transplantation. Among the 15 patients not given immunoglobulin CMV was isolated in three, and two of them developed clinical CMV disease. In addition, one more patient developed CMV antibodies without virus isolation. In five of the 13 patients given immunoglobulin the virus could be isolated, and four of them developed CMV disease. One additional patient showed seroconversion but no other findings of CMV infection. The incidence of acute and chronic GVHD was similar in the two arms. There was no significant difference in survival. In conclusion, the present results do not indicate a beneficial effect of CMV hyperimmune globulin infusions in the prophylaxis of CMV infection or disease in seronegative allogeneic bone marrow transplant recipients from a seropositive donor.

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.

Ocular findings in allogeneic stem cell transplantation without total body irradiation

OBJECTIVE To evaluate the ophthalmologic complications in hematologic patients after allogeneic stem cell transplantation (ASCT) without total body irradiation. DESIGN Retrospective noncomparative case series. PARTICIPANTS A total of 150 ASCT patients. INTERVENTION Ophthalmologic examinations of 130/150 patients were made, with particular attention to the occurrence of graft-versus-host disease (GVHD). RESULTS One hundred thirty patients with a mean age of 35.5 (SD 10.6) years at the time of ASCT were followed up for a mean of 12 months (range 3-60 months). GVHD developed in 73 patients (56.2%). Of 130 patients, 52 (40.0%) had ocular complications, and 29 (22.3%) of those had GVHD. Keratoconjunctivitis sicca was diagnosed in 13 (10.0%) patients, and 12 (9.2%) had different stages of pseudomembranous conjunctivitis. Cataract developed in 3 patients (2.3%) in the observation period, and 7 (5.4%) had keratitis. Six (4.6%) patients had uveitis, and 8 (6.2%) had retinal hemorrhages. No ischemic retinopathy was found. Bilateral optic disc edema developed in 10 (7.7%) patients. CONCLUSIONS Fewer ocular complications were observed in this series than in earlier studies, and the visual outcome was favorable. Cyclosporine has been linked to the development of optic disc edema and ischemic retinal lesions. The latter condition was not observed in the study patients, and the optic disc edema resolved within 1 year in all patients without any detectable visual impairment, in spite of continuation of the drug. Seven patients had acute GVHD at the time of optic disc edema, which is considered to be another manifestation of acute GVHD.

Donation of stem cells from blood or bone marrow: results of a randomised study of safety and complaints

Biological consequences and physical complaints were compared for donors randomly assigned either to blood stem cell (BSC) or bone marrow (BM) donation. In the period 1994–1999, 61 consecutive donors were included. The BSC donors were given G-CSF 10 μg/kg s.c., daily during 5 days before the first leukapheresis. Nineteen donors had one leukapheresis, 10 required two and one donor needed three leukaphereses in order to reach the target cell number of 2 × 106 CD34+ cells/kg bw of the recipient. A median platelet nadir of 102 × 109/l was reached shortly after the last leukapheresis. Three weeks post harvest, 17 of 30 BSC donors had a mild leukopenia. Six had a leukopenia lasting more than a year before returning to normal values. Both groups were monitored prospectively through a standardised questionnaire completed by the donors. BSC donation was significantly less burdensome than BM donation and was preferred by the donors. The short-term risks of BSC mobilisation and harvest seem negligible. The potential long-term effects of G-CSF are unresolved and the donors must be followed closely.Bone Marrow Transplantation (2002) 29, 479–486. doi:10.1038/sj.bmt.1703418