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

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

Incidence of thyroid cancer in the Kingdom of Saudi Arabia, 2000-2010

Thyroid cancer is the second most common malignancy among females at King Faisal Specialist Hospital and Research Centre [KFSH and RC] and in Saudi Arabia, accounting for about 11% of all newly diagnosed female cancers in the country in 2008. Over the past several decades, an increasing incidence of thyroid cancer has been reported in the Kingdom of Saudi Arabia. There are no comprehensive clinical epidemiological data for the trends of thyroid cancer incidence compared to the global incidence. This report reviews the thyroid cancer incidence in KFSH and RC and compares that with Saudi Arabia, the Gulf region, North America and globally from 2000 to 2010. Retrospective review of patients with thyroid cancer was carried out from 2000 to 2010, using the hospital Tumor Registry program as per the American College of Surgeons standards. Trends and patterns of all well-known prognostic factors were sub-stratified by age, stage and grade. A total of 2292 patients with thyroid cancer were treated at KFSH and RC, Riyadh, Saudi Arabia, from 2000 to 2010. Thyroid cancer constitutes about 9% of all malignancies and 12% of all female malignancies at KFSH and RC, which are significantly higher compared to the USA, where thyroid cancer represents only 2.9% of all malignancies and 4.6% of all female malignancies. Papillary adenocarcinoma was the most common histological subtype followed by papillary carcinoma, follicular variant. Median age at diagnosis was 40 for females and 44 years for males. Overall Age-Standardized Incidence Rate [ASR] was 4.4/100,000 [6.8 for female and 2/100,000 for males] in the Kingdom in 2008. Median age at diagnosis was 38 years and the highest incidence was in the 30-39 year age group in KFSH and RC. About 48% of patients presented in the localized stage and 60% underwent combined modality treatment consisting of surgery, radiation and hormonal therapy. There was significantly increased incidence among females as compared to males. The age-adjusted thyroid cancer incidence rates from 2000 to 2010 varied three-fold more for females than for males. Considerable geographical variations were present in thyroid cancer incidence in Saudi Arabia. Thyroid cancer incidence rates have increased exponentially between 2000 and 2010 and there is significant geographical variation in the incidence of thyroid cancer throughout the Kingdom. Thyroid cancer has become the second most common cancer among young Saudi women with a male to female ratio at 0.3:1. Rising incidence of thyroid cancer in Saudi Arabia may be due to the increased detection and diagnosis of the thyroid cancers and not only an increase in the true occurrence of thyroid cancer. More studies are required to determine this significant difference at the molecular level

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

Myeloid sarcoma of the vulva post-bone marrow transplant presenting as isolated extramedullary relapse in a patient with acute myeloid leukemia

Myeloid sarcoma is a tumor of myoblasts or immature myeloid cells occurring in an extramedullary site. Myeloid sarcoma of the female genital tract as an isolated initial presentation or isolated relapse is very rare as evidenced from a literature review. We report a case of vulvar myeloid sarcoma presenting as isolated relapse of acute myeloid leukemia [AML] after allogeneic hematopoietic stem cell transplant [HSCT]. A 41-year-old female diagnosed with AML M5 achieved remission with chemotherapy and underwent allogeneic HSCT from an HLA-matched sibling donor. The post-transplant period was complicated with chronic graft-versus-host disease. At 10 months post-transplant, she presented with a vulvar mass of six weeks duration. Excisional biopsy of the vulvar mass confirmed the diagnosis of myeloid sarcoma as extramedullary relapse. Bone marrow biopsy was without evidence of leukemia. Involvement of the vulva, vaginal and adjacent cervical area only was confirmed. She received re-induction chemotherapy with clinical regression of both the vulvar, vaginal and the cervical masses; this was followed by radiation therapy to an extramedullary site. The correct diagnosis of myeloid sarcoma, particularly of an isolated mass in the genital area, is important because of its rarity and the need for appropriate institution of therapy

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

Defecation of a "colon cast" as a rare presentation of acute graft-versus-host disease

Diffuse involvement of the gastrointestinal tract by graft versus host disease [GVHD] is a common complication of allogeneic hematopoietic stem cell transplant [HSCT]. Gastrointestinal GVHD usually presents 3 or more weeks after HSCT and is characterized by profuse diarrhea, anorexia, nausea, vomiting, abdominal pain and gastrointestinal bleeding. We report a case of a 23-year-old male who had undergone allogeneic HSCT and presented with bloody diarrhea on the 90th day post-HSCT. On the fourth day of admission, the patient passed per rectum a 27-cm long pinkish colored fleshy material recognized as a "colon cast". Sigmoidoscopy showed a congested and erythematous rectum with the remaining portion of the "colon cast" attached to the proximal part of the sigmoid colon. A biopsy from the rectal wall was suggestive of grade IV GVHD. The patient was treated with methylprednisolone, cyclosporin and mycophenolate mofetil, with a partial response [diarrhea and abdominal pain improved], but then he developed multiple other medical complications and died after 3 months

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

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