Page 491 - Hematology_ Basic Principles and Practice ( PDFDrive )

412 Part IV Disorders of Hematopoietic Cell Development

Immunosuppression Versus Bone expense and availability of transplantation, and risk factors such as active
infections, advanced age, or a heavy transfusion burden lead most
Marrow Transplantation patients to automatically undergo treatment with ATG/CSA. For a few
patients with AA, a choice does exist between transplantation and
Immunosuppression and transplantation are both effective therapies for immunosuppressive therapy. BM transplantation offers a permanent
AA (Figs. 30.12 and 30.13). Lack of a matched sibling donor, the cure. Its disadvantages are cost, procedure-related morbidity and mortal-
ity (especially GVHD in older patients), and an increased incidence of
A solid organ malignancies. Immunosuppressive therapy is easier and
100 initially cheaper. However, many patients do not achieve normal blood
“Untransfused patients” (n = 50) cell counts and remain at high risk for relapse and the more serious
complications of late-onset clonal hematologic disease, especially MDS.
80 Retrospective analyses of the large number of European patients
Sustained graft (n = 181) reported to the EGBMT show consistently improved results with
% Surviving 60 advantage for transplantation over immunosuppression. Single-center
both therapies but have repeatedly failed to demonstrate a survival
studies are similar. Certain categories of patients, defined by neutro-
40
phil number and age, probably benefit from one therapy or the other.
Seattle
In general BM transplantation yields superior results in children,
20 Graft rejection (n = 44) immunosuppression in older adults
Remarkable improvements in results using unrelated donors have
made this approach available to many patients who lack a sibling
0 donor. Increasingly, children who have failed a single course of
0 2 4 6 8 10 12 14
B Years immunosuppression and adults refractory to multiple courses of ATG
are offered this procedure, and some transplant groups advocate for
100 early MUD or even haploidentical donor transplant, even before a
trial of immunosuppression.
80
Transplant (n = 218) Androgens
% Surviving 60 ALG (n = 291) Testosterone and synthetic anabolic steroids appeared to be major

advances in the treatment of AA when they were introduced in
40
the 1960s. The high response rates in some early series may be
20 EGBMT retrospectively attributed to the inclusion of patients with moderate
acquired and constitutional AA. For severe AA, controlled trials in
general have not demonstrated efficacy, as measured by survival rates
0
0 1 2 3 4 5 6
C Years
100 A Time to increase ANC by 1000/µL
(in recovered patients)
6
80 Utah, total (n = 99) 5
% Surviving 60 “Controls” Number of patients 4
3
40
AA Utah, extrapolated severe 2
20 study 1
group, 0
nontransplanted (n = 31) Time to increase ANC to >1000/µL
0 B (if initial ANC <200 µL)
0 1 2 3 4 5 6
Years
Fig. 30.12 ACTUARIAL SURVIVAL RATES FOR PATIENTS WITH 4
APLASTIC ANEMIA. (A) Data on bone marrow transplantation from the Number of patients 5
3
University of Washington. (B) Data from the EGBMT on bone marrow
transplantation versus immunosuppression with ALG. (C) Natural history as 2
indicated by survival with supportive and other treatments. Two groups are 1
illustrated. Extrapolated survival curves for patients with severe disease are
derived from retrospective reviews from the University of Utah of 101 records 0 10 20 30 40 50 60 70 80 90
collected from the late 1940s to early 1970s. The patients received blood
transfusions and, later in this period, also received platelets. Almost all were Time (days)
treated with corticosteroids, and one-half were also treated with androgens. Fig. 30.13 TIME TO RESPONSE AFTER TREATMENT WITH ANTI-
Data for patients who did not receive transplants come from a multicenter LYMPHOCYTE GLOBULIN. (A) Distribution of patients with severe
study of the efficacy of marrow transplantation performed in the early 1970s; aplastic anemia by time to achieve an increase in the absolute neutrophil
3
this control group was treated with androgens. AA, Aplastic anemia; ALG, count of 1000 cells/mm . (B) Distribution of patients with an initial absolute
3
antilymphocyte globulin; EGBMT, European Group for Bone Marrow neutrophil count of less than 200 cells/mm by time to achieve an absolute
3
Transplantation. neutrophil count of 1000 cells/mm . ANC, absolute neutrophil count.