ABSTRACT
Busulfan [Bu]-based preparative regimens in hematopoietic stem cell transplantation are commonly used. Previous studies have shown that Bu at a fixed dose of 3.2 mg/kg/day [FBD] given intravenously decreases variability in drug pharmacokinetics and this decreases the dependency on therapeutic drug monitoring [TDM] of Bu. We compared the Bu dose given using TDM with the FBD of 3.2 mg/kg/day. Seventy-three patients with acute leukemia, myelodysplasia, chronic myeloid leukemia, thalassemia major, and sickle cell disease were included. The mean age at transplant was 15 years [range 2-55 years] with 57% adults. Indication for transplantation was leukemia/myelodysplastic syndrome in 46% of the patients, while the remaining 54% were transplanted for inherited blood disorders. We found that the median FBD was lower than the median TDM dose by 39 mg/day with a statistically significant difference [p < 0.001] even after adjusting for the weight [median total FBD of 349 mg, median TDM dose of 494 mg, p < 0.0001]. Age and underlying condition [malignant vs. nonmalignant] were the main factors affecting Bu clearance [p < 0.001 and p < 0.07, respectively]. TDM remains an important tool for the appropriate dosing of Bu in preparative regimens of hematopoietic stem cell transplantation, especially in populations with genetic admixture
ABSTRACT
The Eastern Mediterranean Bone Marrow Transplantation [EMBMT] Group has accumulated over 25 years of data and experience in hematopoietic stem cell transplantation [HSCT], most particularly in he-moglobinopathies, severe aplastic anemia [SAA], and inherited metabolic and immune disorders, in addition to hematologic malignancies peculiar to the region and where recent updates in trends in activities are warranted. To study trends in HSCT activities in the World Health Organization-Eastern Mediterranean [EM] region surveyed by EMBMT between 2008 and 2009. STUDY DESIGN: Retrospective analysis of the survey data, mainly of the cumulative number of transplants, types of transplants [autologous vs. allogeneic], types of conditioning as myeloablative [MAC] vs. reduced intensity conditioning [RIC] and trends in leukemias, hemo-globinopathies, SAA, inherited bone marrow failure syndromes amongst others. Fourteen teams from ten Eastern Mediterranean Region Organization [EMRO] countries reported their data [100% return rate] to the EMBMT for the years 2008-2009 with a total of 2608 first HSCT [1286 in 2008; 1322 in 2009]. Allogeneic HSCT represented the majority [63%] in both years. The main indications for allogeneic HSCT were acute leukemias [732; 44%], bone marrow failure syndromes [331, 20%], hemoglobinopathies [255; 15%] and immune deficiencies [90; 5%]. There was a progressive increase in the proportions of chronic myeloid leukemia [CML] cases transplanted beyond the first chronic phase [3; 7% of all CML cases in 2008 vs 13; 29% in 2009]. The main indications for autologous transplants were plasma cell disorders [345; 36%] Hodgkin disease [256; 27%], non-Hodgkin lymphoma [207; 22%] and solid tumors [83; 9%]. RIC continued to show a progressive increase over the years [7% in 2007, 11% in 2008 and 13% in 2009], yet remained relatively low compared to contemporary practices in Europe published by EBMT. The vast majority [95%] of allo-HSCT sources were from sibling donors with a continued dominance of peripheral blood [PB] [1076; 63%], while cord blood transplant [CBT] increased to 83 [5% of allo-HSCT], matched unrelated donor [MUD] remained underutilized [1; 0%] and there were no haploidentical transplants reported. Large centers with >50 HSCT/year showed a plateau of the total number of allo-HSCT over the last 5 years that may be related to capacity issues and needs further study. There is an overall increased rate of HSCT in the EMRO region with a significant increase in utilization of CBT and allogeneic PB-HSCT as a valuable source. However, further research on outcome data and development of regional donor banks [CB and MUD] may help facilitate future planning to satisfy the regional needs and increase collaboration within the group and globally
Subject(s)
Humans , Retrospective Studies , Health Surveys , Transplantation, Homologous , Transplantation, AutologousABSTRACT
It is more than 20 years since the first cord blood transplant [CBT] was performed, following the realisation that cord blood [CB], which is normally wasted, is rich in progenitor cells and capable of rescuing haematopoiesis. Since then it has been appreciated that CB is rich in stem cells, and has many other features not the least of which is its ability to rescue the transplanted patient without a rigid need for full human lymphocyte antigen [HLA] compatibility. Also it is easily accessible, relatively free from infections and poses no medical risk to the donor. However, the quantity of the stem cells is rather small, thus predominantly restricting its use to children or adults requiring double units. In Oman, we have taken a keen interest in stem cell research and also CBT. We see such activities as an avenue for our patients, for whom a compatible bone marrow [BM] or a peripheral blood donor cannot be found, to have an alternative in the form of CBT. This has encouraged us to establish a national voluntary cord blood bank [CBB] which is a valuable option open to a selected group of patients, as compared to the controversial private CBB. This national CBB will have a better representation of HLA-types common in the region, an improvement on relying on banks in other countries. Considering the need for stem cell transplant/therapy in this country, it is only appropriate that this sort of bank is established to cater for some of these requirements
Subject(s)
Fetal Blood/cytology , Blood Banks , Tissue and Organ Harvesting , Transplantation, Autologous , Histocompatibility Testing , Histocompatibility AntigensABSTRACT
Donor lymphocyte infusion [DLI] is nowadays routinely used for inducing remission in patients who relapse into chronic myeloid leukaemia [CML] after allogeneic bone marrow transplantation. In the present case, it took more than 10 months and several DLI along with alpha interferon injection for development of post DLI acute GVHD and remission of the disease. One of the surprising findings was development of accelerated phase like symptoms and blood picture with rising white cell counts, rising basophils, eosinophils and circulating blast cells when the patient developed acute GVHD. Clinically the patient also developed 8 cms enlarged tender splenomegaly at the same time. After a short period of acute GVHD and accelerated phase like blood picture, he entered into clinical and haematological remission with mild persistent chronic GVHD in the skin and mouth. The present case showed that DLI may need to be repeated several times and persistence may often be rewarded