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

Establishing an autologous versus allogeneic hematopoietic cell transplant program in nations with emerging economies

More than 70,000 hematopoietic cell transplants are currently performed each year, and these continue to increase every year. However, there is a significant variation in the number of absolute transplants and transplant rates between centers, countries, and global regions. The prospect for emerging countries to develop a hematopoietic cell transplantation [HCT] program, as well as to decide on whether autologous HCT [auto-HCT] or allogeneic HCT [allo-HCT] should be established to start with, relies heavily on factors that can explain differences between these two procedures. Major factors that will influence a decision about establishing the type of HCT program are macroeconomic factors such as organization of the healthcare network, available resources and infrastructure. Prevalence of specific diseases in the region as well genetic background of donors and recipients will also influence the mandate or priority of the HCT in the national healthcare plan to explain some of the country-specific differences. Furthermore, microeconomic factors play a role, such as center-specific experience in treating various disorders requiring hematopoietic stem cell transplantation, along with accreditation status and patient volume. The objective of the transplant procedure was to improve the survival and quality of life of patients. The regional difference that one notices in emerging countries about the higher number of allo-HCT compared with auto-HCT procedures performed is primarily based on suboptimal healthcare network in treating various malignant disorders that are the primary indication for auto-stem cell transplantation. In this context, nonmalignant disorders such as bone marrow failure syndromes, inherited genetic disorders and hemoglobinopathies have become the major indication for stem cell transplantation. Better understanding of these factors will assist in establishing new transplant centers in the emerging countries to achieve their specific objectives and positive outcome

Hematopoietic cell transplantation: training challenges and potential opportunities through networking and integration of modern technologies to the practice setting

Hematopoietic cell transplantation [HCT], particularly allogeneic HCT, is a complex and a high-risk procedure requiring expertise to manage potential treatment complications. Published data supports the value of quality management systems in improving post-transplant outcomes; however, there are no universally established, or agreed upon, criteria to assess adequacy of training of physicians, transplant or nontransplant, and supporting staff, among others. It is of paramount importance for transplant centers to identify the needed area[s] of expertise in order to seek appropriate training for their staff. Moreover, transplant physicians need to keep up-to-date with the rapidly occurring advances in the field. Outcomes of patients undergoing HCT are affected by various factors related to patient, disease, procedure, preventative, and supportive strategies, among others. Accordingly, availability of databases is necessary to collect information on these variables and use to benchmark future prospective clinical trials aiming at further improving clinical outcomes. Twinning with leading centers worldwide is helping to not only bridge the survival gap of patients diagnosed with cancer in the developing vis-à-vis the developed world, but eventually closing it. The advent of the World Wide Web and revolution in telecommunication has made access to information more readily available to various sectors including healthcare. Telemedicine is enabling healthcare delivery to remote and underserved geographic areas. In the setting of HCT, ensuring compliance to prescribed therapies and post-transplant surveillance are some areas where implementing telemedicine programs could fulfill an unmet need

Current concepts on hematopoietic stem cell transplantation outcome registries; emphases on resource requirements for new registries

There is tremendous variability in size, scope, and resource requirements for registries depending on the number of patients and participating sites. The outcome registries are organized systems to collect uniform data using an observational study methodology. Patient registries are used to determine specified outcomes for a population for predetermined scientific, clinical, or policy purposes. Historically, outcome registries established in the development of hematopoietic stem cell transplantation [HSCT] have now evolved into myriads of locoregional and international transplant activity and outcome resources. Over time, these registries have contributed immensely in determining trends, patterns, and treatment outcomes in HSCT. There is wider variation in the goals, mission, objectives, and outcomes of the ongoing registries depending on the organizational structure. There is a growing trend toward overarching relationship of these registries to serve as complementary and interoperable resources for high potential collaborative research. In addition to capacity building, standardized, accredited, and optimally operational registries can provide unmatched and unparalleled research data that cannot be obtained otherwise. Moving forward, HSCT data collection, collation, and interpretation should be an integral part of the treatment rather than an option. Quality assurance and continuous quality improvement of the data are pivotal for credibility, measurable/quantifiable outcomes, clinically significant impact, and setting new benchmarks

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

Ocular manifestations of graft-versus-host disease

Allogeneic hematopoietic stem cell transplantation [HSCT] has evolved over the past two decades to become the standard of care for hematologic and lymphoid malignancies. Major ocular complications after allogeneic HSCT have been increasing in number and severity. Graft-versus-host disease [GVHD] remains a major cause of ocular morbidity after allogeneic HSCT. The main objective of this review is to elucidate the ocular complications in patients developing GVHD following HSCT. Ocular complications secondary to GVHD are common and include dry eye syndrome, acquisition of ocular allergy from donors with allergic disorders. Eyelid changes may occur in GVHD leading to scleroderma-like changes. Patients may develop poliosis, madarosis, vitiligo, lagophthalmos, and entropion. The cornea may show filamentary keratitis, superficial punctate keratitis, corneal ulcers, and peripheral corneal melting which may lead to perforation in severe cases. Scleritis may also occur which can be anterior or posterior. Keratoconjunctivis sicca appears to be the most common presentation of GVHD. The lacrimal glands may be involved with mononuclear cell infiltration of both the major and accessory lacrimal glands and decrease in tear production. Severe dry eye syndrome in patients with GVHD may develop conjunctival scarring, keratinization, and cicatrization of the conjunctiva. Therapy of GVHD includes systemic immunosuppression and local therapy. Surgical treatment in refractory cases includes surgical intervention to improve the manifestation of GVHD of the eye. This may include tarsorrhapy, prose lenses, punctal occlusions and corneal transplantation

Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation

Advances in hematopoietic cell transplantation [HCT] technology and supportive care techniques have led to improvements in long-term survival after HCT. Emerging indications for transplantation, introduction of newer graft sources [eg, umbilical cord blood] and transplantation of older patients using less intense conditioning regimens have also contributed to an increase in the number of HCT survivors. These survivors are at risk for developing late complications secondary to pre-, peri-, and posttransplantation exposures and risk factors. Guidelines for screening and preventive practices for HCT survivors were published in 2006. An international group of transplantation experts was convened in 2011 to review contemporary literature and update the recommendations while considering the changing practice of transplantation and international applicability of these guidelines. This review provides the updated recommendations for screening and preventive practices for pediatric and adult survivors of autologous and allogeneic HCT

Successful treatment of steroid-refractory autoimmune thrombocytopenia associated with Castleman disease with anti-CD-20 antibody [rituximab]

Multicentric Castleman disease [MCD] is a lymphoproliferative disorder of incompletely understood etiology and with various clinical presentations. The best therapeutic option for this disease is not well established. MCD is known to be associated with autoimmune phenomena. A 70-year-old female patient of MCD with progressive nodal disease associated with autoimmune thrombocytopenia failed steroid treatment and showed a transient response to intravenous immunoglobulin. The patient achieved complete recovery of her platelet count and a very good response in nodal disease after 3 weekly doses of anti-CD-20 antibody [rituximab]. Anti-CD20 antibody treatment could be a good therapeutic option for MCD, mainly when associated with immune-related disorders

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

Maternal acute lymphocytic leukemia with rearrangement of the mixed lineage leukemia gene occurring during pregnancy

Acute lymphoblastic leukemia [ALL] is a relatively rare disease during pregnancy, accounting for about 15% of all cases of pregnancy-associated leukemia. Although mixed lineage leukemia gene [MLL] rearrangement is the dominant genetic aberration in infantile acute leukemia, the occurrence of MLL gene rearrangement in maternal ALL occurring during pregnancy has not been reported. Out of 31 cases of maternal leukemia diagnosed during pregnancy at our institution, 5 were ALL cases. Three of the 5 patients had MLL gene rearrangement. The data for these 5 patients are presented in this report. We believe that the association of MLL gene rearrangement with maternal leukemia is biologically plausible and this observation needs to be validated in a larger cohort of pregnancy-associated maternal leukemia cases

Autologous bone marrow transplanation for extramedullary plasmacytoma presenting as adrenal incidentaloma

Extramedullary adrenal plasmacytoma [EMP] involving the adrenal glands is rarely encountered clinicaly. We report a A 47-year-old male who presented with bilateral adrenal incidentalomas. After confirming EMP, the patient received two consecutive autologous hematopoietic stem cell transplants [HSCT] using high-dose melphalan. Following HSCT, a serial follow-up helical CT revealed a substantial decrease in the size of both adrenal masses. Serial periodic serum protein and urine electrophoresis and immunofixation showed abrogation of a previously noted monoclonal band. At 50 months follow-up the patient was alive and well. Our patient is the first with EMP to have received an autologous HSCT, which may prove to have a role in therapy due to the immunological effect of the infused donor marrow T-lymphocytes against the clonal proliferation of abnormal plasma cells in extrammedullary sites. This case indicates that an EMP should be added to the differential diagnosis of adrenal incidentalomas

Cancer prevention and control in the eastern mediterranean region: the need for a public health approach

Cancer is increasingly recognized as a major health Concern in the Eastern Mediterranean [EM] region. The emergence of cancer and other non-communicable diseases [NCDs] in most EM region countries is related to increases in life expectancy, an increasing proportion of elderly people, and the successful control of most childhood communicable diseases, along with rapid strides in socioeconomic development. In the next 15 years, cancer incidence in the EM is expected to increase by 100% to 180%, according to World Health Organization [WHO] projection modelling, the largest increase foreseen among developing countries. Even though 30% of cancers can be prevented and controlled using available knowledge, death rates will increase by 17% by 2015 because of the challenges and barriers to implementing national strategic action plans. Other problems facing countries in the region are the lack of national cancer surveillance and little harmonization in monitoring and surveillance methodologies. Data on cancer mortality in the 21 countries is limited or lacking, with only 7 countries having national population-based registries. There is no linking of cancer mortality data to NCD prevention and control. A model of integrated care for NCD prevention programs in general and cancer in particular is lacking, and finally, there is inadequate national capacity-building and a lack of program sustainability. The WHO Regional Committee for the EM has adopted a resolution recognizing the considerable magnitude of cancer as a major cause of morbidity, human suffering, and mortality in the region. In the last 15 years, the WHO Cancer Control Programme has fostered the development of national cancer control programs as a primary intervention strategy for a comprehensive and cost-effective approach at the country level

challenge of risk stratification in acute myeloid leukemia with normal karyotype

Cytogenetic aberrations have long been recognized as the most important prognostic variable in acute myeloid leukemia [AML] and are now a major stratification tool for post-remission therapy. Cytogenetics-based stratification improves survival. Patients with AML and normal cytogenetics, the largest single subgroup, have had a very heterogeneous outcome with standard chemotherapy in multiple clinical trials. Hence it is difficult to recommend a [one size fits all] kind of treatment for this heterogeneous population of AML patients. New emerging data from preclinical, retrospective, and large, randomized controlled studies indicate that in addition to cytogenetic abnormalities, many other molecular aberrations are operative in the response to treatment as well as in the risk of relapse. Such molecular markers are being tested for developing targeted therapies and may help in improved stratification of patients in the selection of post-remission therapy. Emerging evidence reveals that at the submicroscopic level, AML with normal cytogenetics may carry poor prognostic genetic lesions or [molecular signatures] as is the case with FLT3 mutations and overexpression of BAALC, ERG or MN1, or may have aberrations that predict better risk as is the case with isolated NPM1 or CEBPA mutations. Later studies have tried to explore the interaction of various prognostically important genes in this group of AML patients. The utility of the evolving data for bedside management of such patients is expected to improve with the wider application of modern tools, using the proposed clinical outcome models, and probably by development of a risk-scoring system based on the relative risk associated with each molecular aberration. The goals include identifying those patients most likely to benefit from upfront allogeneic HSCT and sparing good-prognosis patients from unnecessary transplant-related morbidity. The following is an outline of the most common molecular changes, their impact on the outcome of AML patients with normal cytogenetics and challenges in their wide scale application in risk stratification