Cost and quality issues in establishing hematopoietic cell transplant program in developing countries

The hematopoietic cell transplant [HCT] activity has grown significantly over the past two decades in both developing and developed countries. Many challenges arise in establishing new HCT programs in developing countries, due to scarcity of resources and manpower in expertise in HCT. While cost issues can potentially hinder establishment of new HCT programs in certain regions, the focus on quality and value should be included in the general vision of leadership before establishing an HCT program. The main challenge in most developing countries is the lack of trained/qualified personnel, enormous start-up costs for a tertiary care center, and quality maintenance. Herein, we discuss the main challenges from a cost and quality perspective which occur at initiation of a new HCT program. We give real world examples of two developing countries that have recently started new HCT programs despite significant financial constraints. We also portray recommendations from the Worldwide Network of Blood and Marrow Transplantation for levels of requirements for a new HCT program. We hope that this review will serve as a general guide for new transplant program leadership with respect to the concerns of balancing high quality with concurrently lowering costs

Leukemia during pregnancy: long term follow up of 32 cases from a single institution

Background and objectives: There is limited information regarding the outcome of patients treated for leukemiaduring pregnancy. This study was performed on all cases of leukemia during pregnancy identified in our institution leukemia database

Patients and Methods: It is a retrospective study from our existing database. Thirty two cases were identified among the cohort of patients treated for acute and chronic leukemia between January 1991 and July 2003

Results: Among the acute leukemia patients [n = 21], 10 patients [47.6%] received chemotherapy during pregnancy, seven had live birth and three had spontaneous abortion. No teratogenicity or congenital malformations or postnatal complication were reported. The remaining 11 [52.4%] were not given chemotherapy while pregnant; three patients presented after 34 weeks of gestation ending in normal live births and then received chemotherapy and eight patients had abortion before starting chemotherapy. Among the chronic myeloid leukemia [CML] patients [n = 11], nine patients received hydroxyurea, one patient received alfa-interferon and one patient was treated with leukapheresis. Eight patients had normal live births and three patients had abortion. Out of the 32 patients, 18 patients [56.2%] subsequently underwent HLA matched sibling allogeneic stem cell transplantation, seven for acute myeloid leukemia [AML], two for acute lymphocytic leukemia [ALL] and nine for CML. After a median follow up of 16 years, five patients [15.6%] are alive in remission [one from chemotherapy group and four from SCT group]

Conclusions: Our report lends credence to the safety and feasibility of administering anti-leukemic therapy in acute and chronic leukemias during pregnancy although acute leukemia patients had possibly a poor long term outcome compared to non-pregnant patients

simplified method for autologous stem cell transplantation in multiple myeloma

We evaluated the efficacy and safety of non-cryopreserved storage of autologous hematopoietic stem cells with no post-transplant granulocyte colony-stimulating factor [G-CSF] support in adult patients undergoing autologous stem cell transplantation [ASCT] for multiple myeloma [MM]. Retrospective review of patients undergoing ASCT from May 2009 to July 2011. Autologous stem cell were mobilized using G-CSF. Leukapheresis to harvest stem cells was performed on day -2 and -1. The grafts were kept in a conventional blood bank refrigerator at 4°C until reinfusion on day 0. The conditioning regimen consisted of melphalan 200 mg/m[2] in all patients. The post-chemotherapy myeloablative phase was managed without growth factors. Between May 2009 to July 2011, 54 adults with MM were treated in our center in Oran. The median age at ASCT was 55 years [range, 35-65]. There were 37 males and 1 7 females. The median harvested CD34+ cell count was 3.60x10[6]/kg [range, 1.90 to 10.52]. All patients had neutrophil engraftment on the median of day 10 [range, 6-17] and platelet transfusion independence on the median of day 13 [range 9-24]. In the 47 evaluable patients the median post-transplant overall survival had not been reached; the estimated overall survival at 30 months was 93.8% [0.05%], and the estimated disease-free survival at 27 months was 93.6% [0.05%]. High-dose chemotherapy and ASCT using non-cryopreserved stem cells and no G-CSF support is safe and feasible in the treatment of MM under our work conditions in developing countries

Hematopoietic stem cell transplantation in the eastern mediterranean region [EMRO] 2008-2009: report on behalf of the eastern mediterranean bone marrow transplantation [EMBMT] group

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

High efficacy and low toxicity of short-course oral valganciclovir as pre-emptive therapy for hematopoietic stem cell transplant cytomegalovirus infection

Cytomegalovirus [CMV] infection is a major infectious complication post-allogeneic hemato-poietic stem cell transplantation [HSCT]. CMV seropositivity in Eastern Mediterranean and certain Asian countries is reported to be close to 100%; hence, the need for effective pre-emptive treatment strategy that has low toxicity. Valganiciclovir [VGC] is a prodrug of ganciclovir with high biovailability. HSCT patients with documented CMV infection [as defined by positive CMV anti-genemia] were treated as outpatients with VGC at a starting dose of 900 mg once daily for antoher week and treatment was subsequently discontinued. Those who were positive after one week of therapy continued on the twice daily treatment schedule for another week and changed to a daily schedule once they converted to antigenemia negativity. From January 2004 to December 2007, 47 HSCT patients received preemptive treatment with VGC for 61 episodes of CMV infection. The antigenemia range was 1 to 700 infected cells/slide. Complete responses were observed in 92% and 97% after the 1st and 2nd week of treatment, respectively. Three percent of the episodes were considred refractory, requiring alternative therapy. No CMV disease was observed in this cohort. Neutropenia was the main observed toxicity, requiring granulocyte-colony stimulating factor in 8 episodes. Outpatietn treatment of CMV infection with "short-course oral VGC" given as a one week twice dialy treatment and one week once daily maintenance is a highly effective therapy with minimal toxicity. These results require validation in a larger, randomized study

Identification of a novel peptide derived from the M-phase phosphoprotein 11 [MPP11] leukemic antigen recognized by human CD8+ cytotoxic T lymphocytes

There is an urgent need for the development of leukemia-targeted im-munotherapeutic approaches using defined leukemia-associated antigens that are preferentially expressed by most leukemia subtypes and absent or minimally expressed in vital tissues. M-phase phosphoprotein 11 protein [MPP11] is extensively overexpressed in leukemic cells and therefore is considered an attractive target for leukemia T cell therapy. We sought to identify potential CD8+ cytotoxic T lymphocytes that specifically recognised peptides derived from the MPP11 antigen. A computer-based epitope prediction program SYFPEITHI, was used to predict peptides from the MPP11 protein that bind to the most common HLA- A*0201 molecule. Peptide binding capacity to the HLA-A 0201 molecule was measured using the T2 TAP-deficient, HLA-A*0201 -positive cell line. Dendritic cells were pulsed with peptides and then used to generate CD8+ cytotoxic T lymphocytes [CTL]. The CML leukemic cell line K562-A2.1 naturally expressing the MPP11 antigen and engineered to express the HLA-A*0201 molecule was used as the target cell. We have identified a potential HLA-A*0201 binding epitope [STLCQVEPV] named MPP-4 derived from the MPP11 protein which was used to generate a CTL line. Interestingly, this CTL line specifically recognized peptide-loaded target cells in both ELISPOT and cytotoxic assays. Importantly, this CTL line exerted a cytotoxic effect towards the CML leukemic cell line K562-A2.1. This is the first study to describe a novel epitope derived from the MPP11 antigen that has been recognized by human CD8+ CTL