Page 1788 - Hematology_ Basic Principles and Practice ( PDFDrive )

1592 Part X Transplantation

highly motivated and available for additional products. This source cord, and haploidentical donor transplants, but they do not show a
also has the potential for more graft-versus-tumor effects because of definitive advantage for either source of HSCs. 9,10 Most transplant
increased alloreactivity and the potential for a beneficial killer-cell units have therefore developed algorithms for donor selection based
immunoglobulin-like receptor mismatch. A haploidentical donor on local experience and patient characteristics such as size and disease.
also has a lower “cost of goods” for procurement of the product.
Several studies have compared outcomes of mismatched unrelated,
Autologous Transplantation

In autologous transplantation the recipient’s own HSCs are collected
TABLE Hematologic Disorders Treated by Hematopoietic then reinfused after high-dose chemotherapy to produce hemopoietic
103.1 Stem Cell Transplantation reconstitution. This approach allows dose intensification in settings
Hematologic Malignancies Chapters where there is a correlation between dose and tumor response rate
and hematopoietic toxicity is a limiting factor for dose intensification.
Acute lymphoblastic leukemia 65 (pediatric), 66, 104 (adult) HSCs are harvested and cryopreserved and then reinfused after doses
Acute myeloid leukemia 61, 104 (adult), 62 (pediatric) of chemotherapy and radiotherapy that would otherwise be lethal or
Myelodysplasia 61, 104 (adult), 63 (pediatric) require a prolonged period of recovery. In general, autologous trans-
plant is well tolerated, and data from the Center for International
Myeloproliferative disorders 63 (pediatric), 70 (myelofibrosis)
Bone Marrow Transplant Research (CIBMTR) show that the 100-day
8
Chronic lymphocytic leukemia 77, 104 mortality rate is less than 5%. The major cause of failure after
Chronic myeloid leukemia 63 (pediatric), 67 (adult) autologous transplant is relapse of the primary disease. One longer-
term concern is that recipients of autologous transplant have an
Multiple myeloma 86, 104
increased risk of secondary therapy-related myeloid leukemia or
Hodgkin lymphoma 75, 104 (adult), 84 (pediatric) myelodysplastic syndromes (t-MDS/acute myeloid leukemia [AML])
Non-Hodgkin lymphoma 80 (follicular), 81 (mantle cell), although this may also reflect effects of previous treatment. Indeed,
82 (diffuse large B cell), 84 a study that identified a pattern of altered gene expression in patients
(pediatric), 104 (all types) who developed t-MDS/AML after transplant for lymphoma found
Nonmalignant Disorders that the genetic programs associated with t-MDS/AML are perturbed
11
Hemoglobinopathies pre transplant.
Sickle cell disease 42 The most common indications for autologous transplant are cur-
Thalassemia 40 rently myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma,
in which it has been shown in randomized trials or concluded in
Immune deficiencies evidence-based reviews that dose intensification and hemopoietic
SCID 51 rescue result in improved DFS. 12,13 Patients with newly diagnosed
Wiskott–Aldrich syndrome 51 myeloma who are considered potential candidates for autologous
Bone marrow failure syndromes transplant autologous stem cell transplantation are usually treated
Aplastic anemia 30 with two to four cycles of therapy that usually includes an immuno-
Paroxysmal nocturnal 31 modulatory agent and a proteasome inhibitor before proceeding to
14
hemoglobulinuria autograft. High- or intermediate-dose melphalan is the most widely
Fanconi anemia and other 29 used conditioning regimen with patients who are younger than the
inherited bone marrow age of 65 years and do not have significant comorbidities receiving
2
failure syndromes high-dose regimens (200 mg/m ); older patients or those with comor-
2 14
bidities receive a reduced dose regimen (usually 140 mg/m ). The
Neutrophil disorders optimal postautograft therapy is under investigation. A multicenter
Chronic granulomatous disease 50
randomized trial showed no advantage for performing nonmyeloabla-
Histiocytic disorders tive allogeneic HSCT compared with tandem autologous HSCT for
Hemophagocytic 52 patients with standard-risk multiple myeloma, while lenalidomide
15
lymphohistiocytosis maintenance therapy, initiated at day 100 after hematopoietic stem-
Lysosomal storage diseases 53 cell transplantation, was associated with a significantly longer time to
SCID, Severe combined immunodeficiency. disease progression and significantly improved overall survival among
16
patients with myeloma. Current studies are evaluating vaccines
TABLE Donor Choice
103.2
Mismatched Unrelated Donor Haploidentical Donor Cord
Availability Over 80% Over 95% Over 80%
Time to procure 1–4 months Immediate 2–5 days
Engraftment Over 95% Over 95% Over 90% with slower engraftment
GVHD Moderate More genetic disparity but moderate Moderate—may be less acute but
with most modern regimens chronic similar
Availability donor for posttransplant Usually, but takes 2–4 weeks Yes No
immune therapy
Relative cost Moderate Low if unmanipulated product. Moderate Moderate (1 unit) or high (2 units)
if ex vivo selection
Risk of relapse Moderate Higher with regimens that are effective Moderate
in preventing GVHD