Clinical Guide to Transplantation in Lymphoma

Bipin N. Savani, Mohamad Mohty

• Publisher: Wiley-Blackwell
• Year: 2015
• Print ISBN:
  9781118863329
• eBook ISBN:
  9781118863275
• Edition: 1
• Topic: Medicine
• Subtopic: Surgery & Surgical Medicine

The first book on clinical guide to transplantation in lymphoma to present cutting edge knowledge on how to integrate, transplantation and novel therapies in patients with lymphoid malignancies

• Provides practical management guidance on how to integrate, transplantation and novel therapies in patients with lymphoid malignancies
• Covers an overview of transplantation in lymphoma, and management of the lymphoid malignancies
• Discusses organizational aspects of transplant patients and managing a transplant program
• Appendices provide practical quick-reference information on follow-up after autologous and allogenic stem cell transplantation in lymphoma

Section 1
Transplantation in lymphomas

CHAPTER 1
Lymphoma and transplantation: historical perspective

Andrew R. Rezvani

Brief history of hematopoietic cell transplantation

The concept of hematopoietic cell transplantation (HCT) dates back more than 100 years. Writing in the Journal of the American Medical Association in 1896, Quine credited Brown-Séquard and d’Arsonval with proposing the therapeutic infusion of bone marrow to treat leukemia, and summarized anecdotal reports of bone marrow infusion as an adjunct to then-standard treatments such as arsenic for pernicious anemia [1]. Quine also described the first case of inadvertently transmitted blood-borne infection (malaria) in a marrow recipient. Anecdotal reports of marrow infusion continued to appear in the literature, but often used only several milliliters of bone marrow and were unsuccessful [2,3]. Classified animal experiments were carried out by the US Atomic Energy Commission during World War II on the use of HCT to treat radiation exposure (later published in 1950), but these were similarly unsuccessful [4]. The era of modern HCT is generally understood to have originated with the 1949 publication by Jacobson et al. of the observation that mice could survive otherwise lethal irradiation if splenocytes were protected from the radiation and reinfused afterward [5,6]. Subsequent work by Lorenz et al. [7] showed that infusion of bone marrow had similarly protective effects in irradiated mice and guinea pigs. Hematopoietic recovery after marrow infusion was initially hypothesized to derive from a humoral or hormonal factor in the infusate, but in the mid-1950s Main and Prehn and others proved conclusively that donor hematopoietic cells engrafted and persisted in HCT recipient animals [8–11].

The first successful use of HCT to treat leukemia in murine models was reported by Barnes and Loutit in 1956 [12]. These authors outlined the central premises of modern allogeneic HCT: first, that high-dose myeloablative therapy could eliminate hematologic malignancies and, second, that donor hematopoietic cells could mount an immunologic response which would eradicate residual leukemia in the recipient. In 1957, these authors reported that leukemic mice treated with myeloablative irradiation and syngeneic HCT had hematopoietic recovery but died of recurrent leukemia, while mice receiving allogeneic HCT demonstrated eradication of leukemia but died of so-called “secondary disease,” a syndrome of diarrhea and weight loss which would today be recognized as graft-versus-host disease (GVHD) [13,14].

Early efforts at allogeneic HCT in humans were carried out nearly simultaneously by Thomas et al. in the 1950s [15]. However, as the immunologic basis of histocompatibility was poorly understood at the time, these patients did not engraft. In fact, a summary of the first approximately 200 human recipients of allogeneic HCT, published in 1970, found no survivors [16]. During this time, however, a number of breakthroughs in animal models of HCT laid the groundwork for the future success of this approach. Billingham et al. [17,18] described the biological basis of GVHD and alloimmune tolerance, and Uphoff [19] and Lochte et al. [20] described the use of methotrexate to prevent GVHD. Thomas et al. [21,22] pioneered the use of canine models of allogeneic HCT. Perhaps most importantly, advances in the understanding of histocompatibility in both the human and the dog provided a basis for donor–recipient matching, a critical component of successful allogeneic HCT [23–25].

In the setting of these advances, allogeneic HCT in humans was revisited with greater success. By 1975, the Seattle group of investigators summarized the results of 110 patients with acute leukemias or aplastic anemia who had received allogeneic HCT from HLA-identical sibling donors. While deaths from recurrent leukemia, GVHD, and opportunistic infection were common, this report was the first to describe long-term survivors of allogeneic HCT [26,27]. Up to this point, allogeneic HCT had been reserved for patients with refractory leukemia; with the application of this approach to patients in first complete remission, substantial improvements in survival were seen [28]. With the advent of HLA typing, the first unrelated-donor transplant was performed using an HLA-matched volunteer donor in 1979 [29]. From these beginnings, HCT has become a fast-growing and increasingly widely used treatment approach for malignant and non-malignant hematologic disease [30].

Much of the benefit from allogeneic HCT derives from the immune effect of the graft against residual tumor (the graft-versus-tumor, or GVT, effect). In contrast, autologous HCT functions on the principle of dose escalation and relies entirely on high-dose, supralethal chemoradiotherapy to eradicate disease. Autologous hematopoietic cells are infused to rebuild the marrow and circumvent otherwise dose-limiting hematologic toxicity. Autologous HCT developed largely in parallel with allogeneic HCT, although without the barriers of histocompatibility, graft rejection, and GVHD. While a number of anecdotal reports and case series of autologous HCT appeared in the 1950s and 1960s, the first patients reported to be cured of otherwise lethal malignancies by this approach were described by Appelbaum et al. in 1978 [31,32]. Subsequent studies established autologous HCT as a potentially curative treatment for many lymphomas, and as an effective but not curative treatment for multiple myeloma.

History of autologous HCT in non-Hodgkin lymphoma

The curative potential of autologous HCT was first demonstrated in patients with non-Hodgkin lymphoma (NHL) [32,33] , and this approach continues to form a cornerstone of management of relapsed NHL, as described in subsequent chapters. The central principles of autologous HCT for NHL were established in the 1980s. Specifically, chemosensitivity is a key determinant of benefit from autologous HCT; Philip et al. [33] reported as early as 1987 that disease-free survival rates were approximately 40% in patients with chemosensitive relapsed NHL, approximately 20% in those with chemotherapy-refractory disease, and nearly zero for patients with primary refractory NHL who had never achieved complete remission. The benefit of autologous HCT in relapsed aggressive NHL was confirmed in a randomized controlled clinical ...

Table of contents

• Cover
• Title page
• Table of Contents
• List of contributors
• Foreword
• Introduction
• Section 1: Transplantation in lymphomas
• Section 2: Management
• Appendix I: Follow-up calendar after autologous stem cell transplantation in lymphoma
• Appendix II: Follow-up calendar after allogeneic stem cell transplantation in lymphoma
• Index
• End User License Agreement