Umbilical cord blood is an alternative source of hematopoietic stem cells for transplantation. Cord blood units are obtained by collecting blood remaining in the umbilical cord and placenta after the delivery of an infant. Umbilical cord blood transplants are less likely to produce GVHD than are hematopoietic cells from adult donors, which allows successful transplants using unrelated units matched for four or five of the six HLA-A, HLA-B, and HLA-DR antigens.⁵ An international network of cord blood banks has been established, with collection of umbilical cord blood from volunteer unrelated donors after delivery of the newborn. Approximately 500,000 umbilical cord blood units are available worldwide. An umbilical cord blood unit provides a relatively low stem cell dose, which results in a slower pace of hematopoietic and immune recovery. Results are improved with higher cell doses and better HLA matching. Adequately matched umbilical cord blood units can be identified for most patients. Initial studies reported better results in children than in adults. A sufficient cell dose cannot be achieved with a single umbilical cord blood unit for most adult recipients; two umbilical cord blood units have been reported to improve outcomes and allow treatment of most adults. Centers focusing on this approach have reported results in children and adults similar to those obtained with matched bone marrow and peripheral blood progenitor cell transplants from unrelated adult donors. A recent registry analysis showed similar results with double umbilical cord blood transplants as with matched or one antigen mismatched unrelated donor peripheral blood progenitor cell transplants.⁶ Because the units are already collected and banked, umbilical cord blood transplants can generally be performed more rapidly than transplants from an unrelated adult donor.

Haploidentical relatives are another potential donor source. Parents, children, and half of siblings are haploidentical, and thus these donors are readily available for most patients. Several centers have reported success with transplantation of T-cell–depleted peripheral blood progenitor cells with a low rate of GVHD.⁷ These transplants are associated with a relatively high rate of rejection, slow immune recovery, and a substantial risk of treatment-related mortality. An alternative approach uses unmodified haploidentical bone marrow transplantation with posttransplant treatment with cyclophosphamide, tacrolimus, and mycophenolate; this regimen produces a low rate of severe acute and chronic GVHD and treatment-related morbidity and mortality.⁸

Recent multicenter studies confirm that successful transplants can be performed in children and adult recipients from either unrelated cord blood or a haploidentical related donor ⁹; overall, results have been similar with each approach and comparable with those reported with matched unrelated donors. Further studies are required to directly compare these strategies and to optimize results of HCT from every donor source. Use of these alternative donors provides an opportunity for treatment of nearly all patients with a clinical indication for HCT. A comparison of different sources of hematopoietic stem cells is presented in Table 30-1.

Table 30-1

Comparison of Different Types of Allogeneic Transplantation

	Related	Unrelated	Cord Blood	Haploidentical
Chances of finding a match	25%	50%	90%	>95%
HLA-matching requirement	Strict (8/8 is optimal; 1 mismatch may be feasible)	Strict (8/8 is optimal; 1 mismatch may be feasible)	Less strict (6/6 is optimal; 1 or 2 mismatches allowed)	Less strict (matched at only one haplotype)
Banking needs	Minimal*	Minimal*	Dedicated CB banks	Minimal*
Time required	15-30 days	3-4 mo	15-30 days	15-30 days
Donor attrition	Unlikely	Likely	Unlikely	Unlikely
Donor safety	Toxicity due to BM harvest or G-CSF	Toxicity due to BM harvest or G-CSF	None	Toxicity due to BM harvest or G-CSF
Type of graft	BM or PB	BM or PB	Cryopreserved CB	BM or PB
Stem cell dose	Standard†	Standard†	Low	Standard†
Graft manipulation	TCD	TCD	None	TCD
Conditioning	Myeloablative conditioning or reduced- intensity conditioning	Myeloablative conditioning or reduced- intensity conditioning	Myeloablative conditioning or reduced- intensity conditioning	Myeloablative conditioning or reduced-intensity conditioning
Engraftment	Standard†	Standard†	Delayed	Delayed
Treatment-related mortality	Standard†	Standard†	High	High
Risk of GVHD	Standard†	Slightly high	Low	High
Availability of additional cells (DLI)	Yes	Yes	None	Yes
Immune reconstitution	Standard†	Standard†	Delayed	Delayed

BM, Bone marrow; CB, cord blood; DLI, donor-lymphocyte infusion; G-CSF, granulocyte colony-stimulating factor; GVHD, graft-versus-host disease; HLA, human-leukocyte antigen; PB, peripheral blood; TCD, T-cell depletion.

^*Grafts are occasionally cryopreserved.

^†For the purpose of this table, results with a related donor transplant are considered standard.

Disease Indications for HCT

Allogeneic HCT can replace defective hematopoietic and immune cells with cells from a normal donor and is indicated to correct severe congenital and acquired bone marrow failure syndromes, metabolic disorders involving hematopoietic cells, and immune deficiency disorders. These disorders include aplastic anemia, hemoglobinopathies, and Fanconi anemia. HCT is also indicated for treatment of severe combined immunodeficiency and other severe immunodeficiency states.

This review focuses on HCT for treatment of cancer. HCT is performed for a wide array of hematologic malignancy and chemotherapy-sensitive solid tumors. Allogeneic HCT is associated with higher treatment-related mortality compared with autologous HCT, but it provides a graft that is free of disease, has a competent immune system, and confers the immune-mediated graft-versus-malignancy effect. Donor lymphocyte infusions (DLIs) can be given to augment this antitumor effect and may induce complete remission (CR) in selected patients with disease relapse after HCT.¹⁰

Several factors are considered when making a decision to perform HCT. A careful evaluation of available nontransplant treatment options is necessary. Communication barriers with the patients should be identified, and patients should be educated about their disease and the risks and potential benefits of HCT, as well as alternative forms of therapy. Once the decision is made to proceed with a transplant, a thorough assessment of factors such as the patient’s age, performance status, disease status, comorbidities, and financial and psychosocial support is necessary.

Because HCT is associated with significant morbidity and mortality, it is generally reserved for life-threatening diseases for which no other satisfactory treatment option exists. As new therapeutic options continue to evolve, so does the role of HCT. The indications for HCT vary by the disease type. Several organizations such as the European Blood and Marrow Transplantation ¹¹ and the National Comprehensive Cancer Network (www.nccn.org) have provided detailed treatment guidelines for specific diseases and clinical settings.

Malignant diseases constitute the most common indication for HCT. Generally, the malignancies that exhibit a marked dose response to myelosuppressive therapy are best treated with HCT. Use of myeloablative conditioning regimens prior to autologous HCT and allogeneic HCT provide the maximum disease response; however, long-term DFS and risk of relapse vary by disease type and status. The toxicity is generally high, particularly in elderly patients. In recent years, use of reduced-intensity conditioning has shown better tolerability and equivalent results to that seen with myeloablative-conditioning HCT. Reduced intensity conditioning HCT primarily relies on the graft-versus-tumor effect for maximal disease control. This approach has allowed transplants to be successfully performed in older patients and in persons with comorbidities that preclude a myeloablative-conditioning transplant.

The indications for HCT vary by disease type. Results are better in patients who have chemosensitive disease or are in remission. Outcomes of HCT are not favorable in patients with poor performance status and who have refractory or progressive disease. Evidence-based reviews have been published by the American Society for Blood and Marrow Transplantation regarding the role of blood and marrow transplantation in the treatment of selected disease.¹² The numbers of patients receiving autologous and allogeneic transplantation for each major indication are shown in Figure 30-1.

Figure 30-1 Disease indications for allogeneic and autologous hematopoietic transplantation. ALL, Acute lymphoblastic leukemia; AML, acute myeloid leukemia; CML, chronic myeloid leukemia; HD; Hodgkin disease; MDS/MPD, myelodysplastic syndrome/myeloproliferative disease; NHL, non-Hodgkin lymphoma.

Acute Myeloid Leukemia

Allogeneic HCT is an optimal treatment for appropriately selected patients with acute myeloid leukemia (AML).¹³ Some centers have also successfully used autologous HCT for patients with AML who are experiencing their first or second remission. Recent advances have allowed risk stratification of patients with AML based on cytogenetic and molecular abnormalities, and this risk stratification helps guide therapeutic decisions.¹⁴ HCT is not recommended for patients in the “favorable” category. Large metaanalyses have shown that availability of an HLA-matched sibling did not result in superior DFS or OS with allogeneic HCT performed in the first period of remission for patients with favorable cytogenetics, t(8;21), inv16, or t(15;17). HCT prolongs DFS in patients with “intermediate-risk” and “high-risk” disease. Patients with diploid cytogenetics are considered intermediate risk, but recent studies have identified prognostically important subgroups based on molecular abnormalities. A large donor versus no-donor analysis of patients with cytogenetically normal AML showed that patients with the prognostically adverse FLT3-internal tandem duplication had improved DFS with allogeneic transplantation.¹⁵ Patients with nucleophosmin (NPM1) or CEBPA mutations without FLT3-internal tandem duplication had a better prognosis with chemotherapy, and there was a similar outcome with HCT compared with standard chemotherapy. HCT can also result in long-term DFS in approximately one third of patients with primary refractory AML.

AML is most common in elderly persons. Reduced intensity conditioning HCT allows for successful transplantation in patients with AML who would otherwise be considered ineligible because of age or comorbidities. Disease relapse is an important concern after HCT. The prognosis of patients who relapse with AML after undergoing a transplant is poor. However, approximately 20% of patients with chemosensitive disease can achieve a durable remission with a second allogeneic transplant ¹⁶ (see Chapter 98).

Myelodysplastic Syndromes

Allogeneic HCT is an established indication for the treatment of myelodysplastic syndromes (MDSs).¹⁷ An international prognosis scoring system (IPSS) is used to classify patients with MDS into low, intermediate-1, intermediate-2, and high-risk categories based on bone marrow blast percentage, karyotype, and cytopenias.¹⁸ A modification of the IPSS system that incorporates a larger number of cytogenetic abnormalities, IPSS-R, was recently presented.¹⁹

Only gold members can continue reading. Log In or Register to continue