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Chapter 104 Indications and Outcomes of Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies in Adults 1597

Indications for Allogeneic Hematopoietic Stem Cell Transplants for Adults in the
United States, 2013

Related Unrelated
2000

1500
Frequency 1000

500

0 AML MDS/MPS NHL ALL CLL MM/PSD CML HD Other Leuk Other Malig

SAA

Primary disease Other Nonmalig
Fig. 104.1 INDICATIONS FOR ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTA-
TION IN ADULTS (US DATA), 2013. ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia;
CLL, chronic lymphocytic leukemia; CML, chronic myeloid leukemia; HD, Hodgkin disease; Leuk, leukemia;
Malig, malignancy; MDS, myelodysplastic syndrome; MM, multiple myeloma; MPS, myeloproliferative
syndrome; NHL, non-Hodgkin lymphoma; PSD, plasma cell dyscrasia; SAA, severe aplastic anemia.

novel conditioning regimens produced a major change in practice in cohort was 35%. However, RIC regimens are increasingly used in
the past decade (Fig. 104.2). patients of all ages receiving both related and unrelated donor trans-
Consensus criteria have been developed by the CIBMTR and the plants, as is shown in Fig. 104.2.
European Society for Blood and Marrow transplantation (EBMT) to Despite the growing popularity of RIC regimens, large retrospec-
distinguish between myeloablative, reduced intensity and nonmye- tive database studies from the EBMT and CIBMTR (summarized in
loablative regimens based on the likelihood of the regimen to produce Table 104.2) have generally failed to show a definite survival advan-
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toxicity to the recipient marrow (Table 104.1). Myeloablative regi- tage resulting from the use of such conditioning regimens. Although
mens produce profound pancytopenia and are usually fatal in the RIC regimens allow a potent graft-versus-leukemia response to occur
absence of stem cell rescue. Nonmyeloablative regimens cause brief with lower toxicity, there are concerns about a higher risk of disease
and often less severe pancytopenia and in the absence of donor stem relapse following RIC regimens. Since the distribution of condition-
cell rescue, autologous hematopoietic recovery is likely to occur. RIC ing regimens in registry studies reflects physician choice or patient
regimens are an intermediate category not fitting well in either of the selection bias, retrospective data are of limited use. Randomized trials
above, since they produce pancytopenia that may recover without have been performed to gauge the true impact of regimen intensity.
stem cell rescue but which is prolonged and, in clinical practice, The US prospective trial Bone Marrow Transplant-Clinical Trial
requires stem cell support. Network (BMT-CTN 0901) randomized patients with myeloid
RIC regimens induce less immune compromise in the immediate malignancies eligible for myeloablative conditioning to RIC-versus-
post-HCT setting as the duration and depth of neutropenia is myeloablative regimens. This trial was suspended after enrolling 272
reduced and host-derived immunocompetent cells are not immedi- out of the planned 356 patients when early results indicated better
ately eliminated. In addition, the reduced risk of organ toxicity makes outcomes for myeloablative regimens (National Heart, Lung and
RIC regimens attractive for patients ineligible for conventional high- Blood Institute clinical advisory and personal communication—Mary
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dose regimens. Whether these benefits outweigh the risks of poten- Horowitz). Detailed results are not available yet and RIC transplants
tially reduced antitumor effects in patients fit for myeloablative remain the standard of care for those not eligible for myeloablative
conditioning regimens, remains controversial. conditioning. A recently concluded prospective European trial
It is generally accepted that reduced intensity regimens allow (RICMAC) showed similar 2-year relapse-free and overall survival for
HCT to be done in some patients who will not be offered HCT with busulfan based RIC versus myeloablative regimens in patients with
myeloablative conditioning. For example, in the US, the proportion MDS and secondary AML. 4
of transplantations done in patients older than 60 years increased
from <5% before 2000 to ~22% in 2013. Two-thirds of the latter
patients received RIC regimens. The Seattle consortium described the GRAFT SOURCES
outcomes of 372 “older” patients (aged 60–75 years) receiving non-
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myeloablative regimens. Increasing age was not associated with The sources of hematopoietic cells for transplantation, historically
increase in organ toxicity or GVHD and 5-year survival of the entire donor bone marrow, now also include peripheral blood hematopoietic