Short-term side effects and attitudes towards second donation: A comparison of related and unrelated haematopoietic stem cell donors.

The Nordic Register of Haematopoietic Stem Cell Donors (NRHSD) has registered related and unrelated donors from 10 transplant centres in Sweden, Norway, Finland and Denmark since 1998. We present a prospective, observational study of 1,957 donors, focusing mainly on the differences between related and unrelated donors. Related donors are reported to have more comorbidities, but similar side effects compared with unrelated donors. Side effects after BM or PBSC donation are generally of short duration and in this study no deaths, myocardial infarctions, splenic ruptures, or thromboembolic events are reported. Interestingly, related donors express more hesitancy towards donating again when asked 1 month after donation.

Extracorporeal photopheresis (photochemotherapy) in the treatment of acute and chronic graft versus host disease: immunological mechanisms and the results from clinical studies.

Extracorporeal photopheresis (ECP) is an immunomodulatory alternative for treatment of graft versus host disease (GVHD). The blood is then separated into its various components through apheresis; buffy coat cells are thereafter treated with 8-methoxypsoralen before exposure to ultraviolet light and finally reinfused into the patient. There is a general agreement that this treatment has an anti-GVHD effect, but the mechanisms of action behind this effect are only partly understood. However, altered maturation of dendritic cells (DC) and thereby indirect modulation of T-cell reactivity seems to be one important mechanism together with DC-presentation of antigens derived from apoptotic donor T cells and induction of regulatory T cells. The treatment has been best studied in patients with chronic GVHD (both pediatric and adult patients), but most studies are not randomized and it is difficult to know whether the treatment is more effective than the alternatives. The clinical studies of ECP in adults with acute GVHD are few and not randomized; it is not possible to judge whether this treatment should be a preferred second- or third-line treatment. There is no evidence for increased risk of leukemia relapse or suppression of specific graft versus leukemia reactivity by this treatment, so specific antileukemic immunotherapy may still be possible. Thus, even though the treatment seems effective in patients with GVHD, further clinical (especially randomized) as well as biological studies with careful standardization of the treatment are needed before it is possible to conclude how ECP should be used in acute and chronic GVHD.

[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.

[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.

Immune reconstitution after allogeneic stem cell transplantation: the impact of stem cell source and graft-versus-host disease.

BACKGROUND AND OBJECTIVES: Bone marrow (BM) and blood stem cell (BSC) allografts differ considerably with respect to their content of progenitor cells and progenitor cell subsets as well as mature lymphocytes. The aim of this prospective, randomized study was to determine whether these differences have an impact on early post-transplant immune recovery. DESIGN AND METHODS: In a prospective randomised study, we found enhanced immune recovery in recipients of BSC allografts compared to in recipients of BM allografts despite transplantation of a lower number of lymphoid progenitors, particularly B-cell progenitors. The large number of mature lymphocytes in BSC allografts is a plausible explanation for this observation. At the progenitor cell level, we found a comparable and very high proportion of progenitor cells involved in lymphopoiesis in both study groups. RESULTS: Patients with extensive chronic GVHD, irrespective of the allograft received, had low immunoglobulin (Ig) levels in serum, low B-cell counts in blood and low numbers of B-cell progenitors in the bone marrow. They also showed high T-cell counts, particularly CD3+CD8+ T-cell counts, which was paralleled by a high number of T-cell progenitors in the bone marrow. In patients with extensive chronic GVHD we found low natural killer (NK)-cell counts which has not been reported previously. INTERPRETATION AND CONCLUSIONS: Early immune recovery is enhanced following BSC allografting compared with BM allografting. This is plausibly explained by the large inoculum of mature lymphocytes in BSC allografts. Following allografting, a higher proportion of the BM progenitor cell compartment is involved in lymphopoiesis than it is in healthy adults. However, B-lymphopoiesis is inhibited in patients with extensive chronic GVHD resulting in impaired B-cell recovery. These patients also seem to show impaired NK-cell recovery.

Eltrombopag in Good's Syndrome.

Good's syndrome is a rare acquired immunodeficiency associated with thymoma. Eltrombopag is a thrombopoietin receptor agonist and has been shown to be a valuable supplement to the treatment of several types of refractory cytopenias. In this paper, we describe a male patient suffering from Good's syndrome with immune-mediated T-cell driven pancytopenia and absence of megakaryopoiesis. He was successfully treated with eltrombopag resulting in a multilineage clinical response.

Malignant phyllodes tumor and acute megakaryoblastic leukemia sharing a common clonal origin.

There is a well-known association in male patients between mediastinal germ cell tumors (GCT) and hematologic malignancies, with a propensity towards acute megakaryoblastic leukemia. These rare malignancies have been shown to share a common clonal origin, often deduced from the finding of isochromosome 12p, i(12p), in cells from both the solid tumor and the leukemia, and thus are now known to represent different manifestations of the same clonal process. We treated a young female patient with a malignant phyllodes tumor followed by an acute megakaryoblastic leukemia and found several of the same marker chromosomes by karyotype analysis of cells from both the tumor and the leukemia implying a common clonal origin of the two. To the best of our knowledge, this has not been demonstrated in phyllodes tumors before, but indicates that the same type of leukemization may occur of this tumor as has been described in mediastinal GCT.

[Hairy cell leukemia treated with cladribine]. / Hårcelleleukemi behandlet med cladribin.

BACKGROUND: Hairy cell leukaemia is a chronic B-cell disorder that follows an indolent course. Cladribine has in the last decade emerged as the drug of choice for treating hairy cell leukaemia. MATERIAL: We report on the long-term follow-up of 26 patients treated from January 1992 to June 1993 with cladribine administered subcutaneously. RESULTS: 25 patients were evaluable for response. 21 patients (84%) achieved complete remission, three patients (12%) achieved partial remission, and one patient had no response. At a median follow-up of 6.8 years, 24 patients (92%) were still alive. One patient died from infections four months after treatment, while the other patient died from a malignant melanoma 4.4 years after treatment. Relapse assessed by flow cytometry was diagnosed in 95% of the patients. 38% of those in complete and 67% of those in partial remission were treated by a second course of cladribine during the follow-up. Retreatment led to normalisation of peripheral blood count in all patients. INTERPRETATION: Cladribine is not a curative treatment in hairy cell leukaemia, but it induces long lasting remission.