History of haematopoietic stem-cell transplantation.

After fifty years of investigations into the use of pluripotent haematopoietic stem-cell transplantation for cancer therapy, this procedure has progressed from one that was thought to be plagued with insurmountable complications to a standard treatment for many haematological malignancies. How have these hurdles been overcome, and how can the therapy be expanded to include patients who are too old or medically infirm to tolerate conventional transplant approaches?

Reduced-intensity conditioning in allogeneic stem cell transplantation for hematological malignancies: a historical perspective.

Allogeneic hematopoietic stem cell transplantation represents a curative treatment approach for a large range of hematologic malignancies. Traditionally, high-dose radiochemotherapy as preparative regimen has been thought to be necessary for successful allogeneic stem cell transplantation. However, high-dose conditioning often results in considerable medullary and extramedullary toxicity, contributing to high rates of treatment-related mortality. This limits the use of this procedure to patients below 60 years of age without significant comorbidities. Since the peak incidence of most hematological malignancies is beyond the 5th decade of life, the majority of patients are not eligible for high-dose treatment. During the last 15 years, several dose-reduced or even non-myeloablative conditioning regimens have been developed, offering a curative treatment option for these patients. This review summarizes the history of reduced-intensity conditioning (RIC) transplantations, depicts the differences among regimens, highlights significant patient factors, and describes the impact on selected hematological malignancies.

Incidence of haematological malignancies in Kosovo-A post "uranium war" concern.

BACKGROUND: During the Kosovo War (1998-99) approximately 31,000 rounds with Depleted Uranium (DU) were fired on 85 targets in Kosovo. The number of haematological malignancies (HM) increased after the war and the concern was the use of DU during the war. The aim of this study was to analyse the incidence rates of HM in Kosovo throughout a 20-year that includes pre- and post- war period (1995-2015); and to examine if there is any association between the use of DU rounds and incidence rates of HM in different regions of Kosovo. METHODS: In this retrospective register-based study, 1,798 new patients diagnosed with leukaemia, Hodgkin lymphoma, non-Hodgkin lymphoma and Multiple myeloma were analysed over a 20 year period. Incidence rates were calculated focusing on specific time periods, regions and age-groups. In addition, the correlation between the use of DU in different regions and their incidence of HM was analysed. RESULTS: The average annual crude rate of all HM in Kosovo was 5.02 cases per 100,000 persons. Incidence rates of HM in first post-war period (2000-2003) increased by 0.37 cases/100,000 persons (9.51%) compared to the pre-war period (1995-1998) whereas in the last post-war period (2012-2015), incidence of HM increased by 3.19/100,000 persons (82%). Gjakova and Peja, the first and third most exposed regions to DU ordnance ranked first and second in difference in HM. Prishtina, Gjilan and Ferizaj, regions with the least number of rounds/km2, were characterized by a decline of incidence rates. CONCLUSIONS: After the war, the increase in incidence rate of HM was higher in two regions with most DU rounds/km2 expended Despite these findings, this study warrants further investigation and does not lead us to a conclusive finding on the existence of a causal relationship between the use of DU during the war and the rise in incidence of HM in Kosovo.

Blood and marrow transplantation: a perspective from the University of Minnesota.

On the occasion of the first meeting of the Robert A. Good Immunology Society in June of 2006, I was asked to provide a perspective on the history and progress of the field of bone marrow transplantation. I was honored to provide this perspective at that meeting and subsequently in this manuscript. This review has a strong University of Minnesota bias, as Minneapolis is a place where important roots in this field were developed. Minnesota is also where I have spent my career in this field learning the excitement of laboratory research beginning as a medical student under Bob Good and Carlos Martinez in 1960, and clinical research in pediatrics under Bill Krivit and Mark Nesbit beginning in 1970. This review is dedicated to two of my recently deceased mentors: Bob Good was a pioneer in so many ways and a true giant in immunology and blood and marrow transplantation. Bill Krivit taught me a great deal about genetic diseases and the critical role of compassion and understanding patients and their families in dealing with fatal illness and new treatments such as bone marrow transplantation that are often risky and themselves may result in suffering and death. My affection for Bob Good and Bill Krivit is unending.

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience.

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue. FUNDING: F. Hoffmann-La Roche Ltd., Basel, Switzerland.

Hematologic malignancies in South Africa 2000-2006: analysis of data reported to the National Cancer Registry.

Little is known about the incidence patterns of hematologic malignancies in Sub-Saharan Africa, including South Africa. We estimated incidence rates of pathology-confirmed adult cases of leukemia, myeloma and related diseases (myeloma), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) reported to the National Cancer Registry of South Africa (NCR) between 2000 and 2006, by age, gender, and population group (Black, White, Coloured, Asian/Indian). Gender-specific age-standardized rates were calculated overall and by population group and incidence rate ratios (IRRs) were estimated using Poisson regression models. Between 2000 and 2006, there were 14662 cases of leukemia, myeloma, HL, and NHL reported to the registry. Incidence rates of reported hematologic malignancies were generally 20-50% higher among males than females. Our analyses suggested marked differences in the rates of reported hematologic malignancies by population group which were most pronounced when comparing the White versus Black population groups (IRRs ranging from 1.6 for myeloma to 3.8 for HL for males and females combined). Challenges related to diagnosis and reporting of cancers may play a role in the patterns observed by population group while the set-up of the NCR (pathology-based) could lead to some degree of under-ascertainment in all groups. This is the first country-wide report of the incidence of hematologic malignancies in South Africa. Despite challenges, it is important to analyze and report available national cancer incidence data to raise awareness of the cancer burden and to characterize patterns by demographic characteristics so as ultimately to improve the provision of cancer-related health care.

Donor lymphocyte infusion following allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Allogeneic hematopoietic stem cell transplantation (SCT) is the treatment of choice for many malignant hematological disorders. Following recent improvements in non-relapse-related mortality rates, relapse has become the commonest cause of treatment failure. Infusion of donor lymphocytes can potentially enhance immune-mediated antitumor activity and offers a salvage option for some patients. This paper reviews the current literature on the efficacy of this therapeutic strategy. AREAS COVERED: The biology of adoptive cellular therapy with allogeneic immune cells to treat relapse across a spectrum of diseases in both the full intensity and reduced intensity hematopoietic SCT settings is explored. The review discusses the current limitations of the approach and reviews several new experimental strategies which aim to segregate the desired graft-versus-tumor effect from the deleterious effects of more widespread graft-versus-host reactivity. EXPERT OPINION: Durable responses to DLI have been noted in chronic myeloid leukemia and responses have also been described in acute leukemia, multiple myeloma and chronic lymphoproliferative disorders. The new challenge in transplantation is to optimize DLI therapy in order to further improve patient outcomes.