Hematopoietic stem cell transplantation in SCD.

Hematopoietic stem cell transplantation (HSCT) is the one and only curative therapy available for patient with severe sickle cell disease (SCD). Until today, several hundreds of patients have undergone geno-identical HSCT. More than 200 patients were transplanted in France. The first indication was cerebral vasculopathy. Among both malignant and non-malignant diseases treated with HSCT, the success rate obtained in SCD patients appears as the best one. From the year 2000, more than 95% of transplanted patients survived the HSCT procedure and more than 90% are completely cured and experience a very satisfying health condition post-transplantation. However, the current standard procedure includes a myeloablative conditioning regimen for warranting engraftment. Such regime is linked to severe long-term side effects such as hypofertility. Due to the excellent obtained results, we have to think about a possible widening of indications, a decrease of conditioning intensity and toxicity, and about HSCT from alternative stem cell sources, such as mismatch family donor, unrelated volunteer donor or unrelated cord blood.

Decision analysis of peripheral blood versus bone marrow hematopoietic stem cells for allogeneic hematopoietic cell transplantation.

Peripheral blood stem cells (PBSCs) and bone marrow (BM) hematopoietic stem cells represent therapeutic alternatives in allogeneic hematopoietic cell transplantation. Randomized controlled trials and an individual patient data meta-analysis (IPDMA) have demonstrated a decreased risk of disease relapse and an increased risk of acute and chronic graft-versus-host disease (aGVHD, cGVHD) in patients receiving PBSCs compared with those receiving BM stem cells. Decision modeling provides quantitative integration of the risks and benefits associated with these alternative treatments, incorporates survival discounts for lower quality of life in patients with aGVHD or cGVHD and post-transplantation relapse, and allows sensitivity analyses for all model assumptions. We have constructed an externally validated Markov model to represent and analyze the decision to use PBSC or BM, estimating post-transplantation state transition probabilities (eg, GVHD and relapse) and quality-of-life discounts from the IPDMA and relevant literature; importantly, this IPDMA synthesized data from primarily adult patients treated with myeloablative (MA) conditioning regimens with T cell-replete matched sibling donors. In this setting, the model demonstrates the superiority of PBSC over BM in both overall and quality-adjusted life expectancy, with a 7-month advantage for PBSC. Sensitivity analyses support this conclusion through a range of values for each variable supported by the IPDMA and quality-of-life discounts, as supported by the literature. However, BM is the optimal strategy in conditions in which the 1-year relapse probability is < 5%. PBSC is the optimal stem cell source in terms of both overall and quality-adjusted life expectancy, except in conditions with a very low relapse probability, in which BM provides optimal outcomes.

Olive oil-based intravenous lipid emulsion in pediatric patients undergoing bone marrow transplantation: a short-term prospective controlled trial.

BACKGROUND & AIMS: Parenteral nutrition (PN) is an important component of the supportive care of children undergoing bone marrow transplantation (BMT). The study aimed to assess short-term safety and metabolic effects of an olive oil-based (OO) lipid emulsion compared with a MCT/LCT (M/L) emulsion in the clinical setting of pediatric BMT. METHODS: Twenty-eight pediatric BMT patients (age 1-18 years) expected to need PN support for at least 2 weeks, were prospectively enrolled and randomly assigned to receive either OO or M/L lipid emulsions within PN. Clinical and routine laboratory parameters, plasma fatty acids profile, vitamin E and peroxidation status were recorded at baseline and after 14 days of PN. RESULTS: No significant differences were found for hematological parameters, liver enzymes, vitamins, plasma peroxidation status, percentage and time to engraftment. Taking into consideration the baseline fatty acids levels, the OO group showed higher oleic acid (p=0.012), linoleic (p=0.012) and arachidonic acid (p=0.002) enrichment but similar eicosapentanoic and docosahexanoic acids levels compared to the M/L group at day 14. Cholesterol levels decreased significantly in the OO group after 14 days on PN (p=0.017). CONCLUSIONS: OO lipid emulsion was well tolerated, maintained essential fatty acids and peroxidation status, and generated a favorable plasma lipid profile. In this study short-term use of OO intravenous lipid emulsions was safe in children who needed PN support during BMT.

The Italian SIdEM registry for apheresis: an overview of the 2005 statistics.

Data collection on apheresis activities in Italy throughout 2005 including techniques, types of blood cell separators, clinical indications and adverse effects was performed by means of a standardized questionnaire. These data provided by 83 Apheresis Units from 16 Italian regions, albeit rough, are sufficiently informative, mainly in comparison with previous surveys on these statistics (1997 and 2000). In 2005 a total number of 204,746 apheresis procedures were carried out, with a clear-cut prevalence of apheresis production (87.7%), performed by 66 out of 83 Apheresis Units (79.5). Lombardy, Veneto and Tuscany were the most active regions for therapeutic apheresis (51.1% of the total national procedures). An increasing number in extracorporeal photochemotherapy as compared to the 2000 national survey (3,386 vs. 704 procedures) is the most striking observation to emerge from the 2005 data collection on therapeutic apheresis in Italy. Adverse effects, predominantly mild ones (i.e., paresthesia due to citrate-induced hypocalcemia), occurred in 0.12% of apheresis production and 6.04 of therapeutic sessions, particularly in the course of peripheral blood stem cell collection (20.79%), as already reported in the 2000 national survey.

Comparable outcomes of matched-related and alternative donor stem cell transplantation for pediatric severe aplastic anemia.

Matched sibling donor (MSD) bone marrow transplantation is the treatment of choice for pediatric patients with severe aplastic anemia (SAA); however, only about 33% of patients will have an HLA-identical sibling. Alternative donor (AD) transplants may be an option for these patients, but such therapies have been associated with greater incidence of graft failure and graft-versus-host disease (GVHD). We retrospectively analyzed 36 pediatric patients who received 38 bone marrow or peripheral blood stem cell transplants (15 MSD and 23 AD) for SAA at our institution from April 1997 to October 2005. Nineteen AD recipients received reduced intensity conditioning with cyclophosphamide, low-dose total body irradiation, and antithymocyte globulin (ATG) or Campath. The 4-year overall survival for MSD recipients was 93% versus 89% for AD recipients treated with reduced intensity conditioning regimens at a median follow-up of 52 months (range, 6-99 months). No patient receiving Campath, compared with 3 of 9 patients receiving ATG, developed extensive, chronic GVHD. We conclude that, for children with SAA, AD transplantation is as effective as MSD transplantation. Further, compared with ATG, preparatory regimens containing Campath may be associated with a lower incidence of extensive, chronic GHVD.

Keynote address: The challenge of thalassemia for the developing countries.

The thalassemias occur at some of their highest frequencies in the developing countries, particularly those of Asia. In many countries, facilities for the control of these conditions are extremely limited. Although a great deal can be done to help the situation by developing further North-South and South-South partnerships for disseminating better practice, the major problem for the future lies in the unwillingness of governments and international health agencies to accept that the thalassemias present a health burden comparable to that of other major diseases in the developing countries. However, preliminary analyses suggest that, at least in the case of Asia, this is not true. Further work of this nature, together with more detailed frequency and economic data, are required to provide solid evidence for the health burden posed by thalassemia in the developing world. Unless this is done, the large populations of patients with thalassemia in these countries will continue to be neglected.

Bone marrow transplantation in adults with thalassemia: Treatment and long-term follow-up.

Current regular blood transfusion programs and chelation treatment have considerably improved survival of patients with thalassemia, which resulted in a larger proportion of adult patients. However, disease- and treatment-related complications in these patients progress over time, causing severe morbidity and shortened life expectancy. Stem cell transplantation still remains the only cure currently available for patients with thalassemia. This study updates transplant outcomes in 107 adult patients with median age of 22 years (range, 17-35 years) who received bone marrow transplantation (BMT) from human leukocyte antigen (HLA)-identical related donors between 1988 and 1996 (group A) and describes the results of BMT in 15 adult patients with median age of 21 years (range, 17-31 years) who were treated with a new treatment protocol (Protocol 26) between 1997 and 2003 (group B). The probability of survival, event-free survival, nonrejection mortality, and rejection for group A patients were 66%, 62%, 37%, and 4%, respectively, with a median follow-up of 12 years (range, 8.3-16.2 years). Group B patients treated with the new protocol had some improvement in thalassemia-free survival (67%) and lower transplant-related mortality (27%) than that of previous protocols. However, transplant-related mortality in these high-risk patients remains elevated. Current myeloablative BMT in adult patients is characterized by higher transplant-related toxicity due to an advanced phase of disease. Although this new approach to transplant adult patients with a reduced-dose intensity-conditioning regimen has improved thalassemia-free survival, transplant-related mortality in these high-risk patients remains elevated.

Bone marrow transplantation for chronic myelogenous leukemia: clinical outcomes.

Marrow transplant is potentially curative therapy for CML. Allogeneic sibling-donor marrow transplant may be the therapy of choice for younger patients early in the course of disease. Early transplant is an important influence on disease-free survival and relapse after related-donor transplant therapy, although additional patient characteristics influencing outcome can be identified and may have cumulative adverse effects. The 5-year disease-free survival of patients transplanted within one year of diagnosis and without signs of advanced disease is greater than 65%. Significant problems remain, however, including early mortality (primarily from infection, pneumonia, and pneumonitis) and relapse of CML following transplant, including late relapse occurring more than 5 years posttransplant. For patients without a matched, related donor, unrelated-donor marrow transplant may be a treatment option and can result in successful outcome for patients with CML. Relapse following unrelated-donor marrow transplant is rare. However, the use of an unrelated donor is associated with significant toxicity, including early mortality, engraftment failure, and ongoing morbidity and mortality associated with acute and chronic graft-versus-host disease. For patients who lack an available matched-related or -unrelated donor, autologous marrow transplant has been developed as an alternative approach to therapy. Long-term survival following autologous marrow transplant is possible and may even approach the survival for allogeneic related-donor recipients, although cure of disease is not achieved.

Report from the International Bone Marrow Transplant Registry and the Autologous Blood and Marrow Transplant Registry--North America.

Bone marrow transplants are an effective treatment for many life-threatening diseases. Considerations for use include potential for cure, availability of a suitable donor, feasibility of using autologous stem cells, and risks of transplant-related mortality. Not addressed in this article, but also important, is consideration of the relative efficacy of conventional therapy in specific settings. The IBMTR and ABMTR offer a unique resource for examining the role of allogeneic and autologous transplants in cancer treatment.

Comparison of peripheral blood stem-cell and autologous bone marrow transplantation for lymphoma patients: a case-controlled analysis of the EBMT Registry data. Lymphoma Working Party of the EBMT.

A case-controlled analysis was performed to assess the effect of stem-cell source on autograft in a group of patients with malignant lymphoma reported to the European Bone Marrow Transplant Group (EBMT). The study was performed matching 83 patients autografted with peripheral blood stem cells (PBSC) with 83 autologous bone marrow transplantation (ABMT) patients. The case-matching was carried out following selection of the main prognostic factors for progression-free survival by multivariate analysis. The progression-free survival was similar in both types of transplants (38.5% PBSCT vs. 36.4% ABMT). The overall relapse and progression rate for the PBSCT was 51.2% compared with 50.1% for the ABMT patients. The differences were not significant statistically. The transplant-related mortality was 6% for both groups. The neutrophil and leucocyte recovery occurred faster in the peripheral blood stem-cell transplantation (PBSCT); the platelet recovery was not significant. A higher number of interstitial pneumonitis and fungal infection episodes were observed in the ABMT group. In conclusion, in these closely matched groups, there is no difference in PFS between patients undergoing PBSCT and those undergoing ABMT. However, the patients autografted with PBSC have a more rapid engraftment and a lower toxicity.

ISHAGE bone marrow processing survey: report on an international information gathering process. International Society for Hematotherapy Graft Engineering.

Significant amounts of information are currently available within the database generated by the responses to the Bone Marrow Processing Survey. As additional Surveys are returned, the data will continue to be entered into a Lotus spreadsheet, until a more sophisticated database with a programmed interface becomes available. The readership is encouraged to enter or edit the databank by returning a completed or amended Survey to the Society. Copies of the form are available from the Society or can be found in the first issue of the Journal of Hematotherapy.

Unrelated bone marrow transplantation in Canada, the national experience. Canadian Red Cross Society.

The Canadian Unrelated Bone Marrow Donor Registry (UBMDR) of the Canadian Red Cross Society (CRCS) was officially funded as of April 1, 1989 for an initial three year period with a mandate to recruit 50,000 unrelated bone marrow donors and to conduct the search activities for unrelated bone marrow donors worldwide on behalf of Canadian patients. Since February of 1988, 162 unrelated bone marrow transplants have been carried out in Canada. The registry now stands at an enrollment of 35,705 with approximately 1,200 donors being added monthly. Recruitment of unrelated bone marrow donors is now established in fourteen Canadian cities, and an active ethnic recruitment is now in progress.

Bone marrow transplantation for acute myeloid leukemia: the EBMT experience. A prospective analysis from HLA-typing. The EMBT Leukemia Working Party.

In 1990, 4,234 BMT were performed in Europe; 2,097 autologous BMT (388 AML) and 2,137 allogeneic BMT (494 AML). Although an established therapy with leukemia free survival (LFS) at five years of 41% +/- 5% (EBMT results) its value compared to alternative therapies remains controversial. During the year 1985, the EBMT conducted a prospective evaluation study. In 12 centres 168 patients with AML were registered at the time of HLA-typing. Basic patient data and treatment intention were recorded. 79 patients were HLA-typed at diagnosis. 68 patients in 1st CR and 21 at other stages. Follow-up of these patients was obtained as of January 1, 1991. Three-year LFS is 44% for patients with an HLA-identical donor and 21% for those without (p = 0.02). Of the 68 patients HLA-typed in first CR, 40 had an HLA-identical donor and 28 no donor. Three-year LFS is 42% and 35%. resp. (n.s.). The difference in results between patients typed at diagnosis and first CR patients illustrates the problem of selection. We conclude that patient registration early in the disease can give insight into the process of selection. Allogeneic BMT incorporated prospectively at diagnosis into therapy offers a survival advantage for patients in this age category compared to alternative therapies.

Costs of bone marrow transplants using unrelated donors.

Bone marrow transplantation is an expensive treatment, rationed primarily by the availability of donors. Recruiting potential unrelated bone marrow donors to a register would add not only to the cost, but also to the volume, of transplantation. Proposals to establish such registries have thus been subject to rigorous financial scrutiny. In Australia, 3 alternative estimates suggest that approximately 200 patients, otherwise suitable for bone marrow transplantation, do not receive transplants because they have no suitable related donor. The population of Australia is approximately 16 million. The alternatives for these patients are thus chemotherapy or unrelated bone marrow transplantation. The costs of chemotherapy and transplantation have been directly compared in 1 trial of treatment for acute nonlymphoblastic leukaemia. The cost per year of life saved was approximately the same for the 2 treatments, with better patient survival from transplantation. The estimated cost difference in both the United States and Australia, between the policy extremes of no patients transplanted, and all transplanted, was between 1.3-2.4% of the total costs of managing these patients. The cost of searching existing registers for unrelated donors for Australian patients, averages A$24,000-28,000 to the point of a successful donor procedure. The cost of establishing and maintaining an Australian Register of a size predicted to find donors for half of the potential recipients, has been estimated at A$ 10,000 per donor procedure. The decision to proceed with unrelated bone marrow transplantation commits resources that are currently used by the alternative therapies. It is thus important to monitor both the costs and effects of the new approach.(ABSTRACT TRUNCATED AT 250 WORDS)