Portada Simposios - Supplements - Haematologica

XLII Reunión Nacional de la AEHH y XVI Congreso de la SETH. Simposios
87
transplant complications between days 54 and 360.
Of 42 patients evaluated, all had persistent donor engraftment
at 2 months posttransplant. Non-fatal
graft rejection subsequently occurred in nine (20 %)
patients. Twenty-nine patients had pretransplant exposure
to intensive chemotherapy or to multiple cycles
of purine analogues, and 28 of them had sustained
donor cell engraftment. Major disease responses
were observed in 16 of 23 (70 %) patients who
had measurable disease pretransplant. These included
all four CML patients with complete molecular
response, 5 of 7 CLL patients, 1 of 1 AML patient,
1 of 1 ALL patient, 2 of 5 MM patients, 2 of 4 HD patients,
and 1 of 3 NHL patients. Four patients with
CML and two with CLL achieved complete molecular
(PCR) remissions. Although follow-up is too short
to assess definitive antitumor effects, this novel approach
dramatically reduced the acute toxicities of
allografting even in elderly patients and has allowed
for the induction of graft-versus-tumor effects, all in
an ambulatory care setting. Modifications of the immunosuppression
should enhance engraftment and
reduce GVHD without significantly increased toxicity,
and thus facilitate further studies of adoptive immunotherapy
in various malignancies and of allografting
for selected nonmalignant diseases. The results have
prompted us to investigate use of these transplants in
other clinical settings, including transplants from
HLA-matched unrelated donors.
References
1. Jacobson LO, Marks EK, Robson MJ, Gaston EO, Zirkle RE. Effect of
spleen protection on mortality following x-irradiation. J Lab Clin Med
1949; 34: 1538-1543.
2. Nowell PC, Cole LJ, Habermeyer JG, Roan PL. Growth and continued
function of rat marrow cells in x-radiated mice. Cancer Res 1956; 16:
258-261.
3. Ford CE, Hamerton JL, Barnes DWH, Loutit JF. Cytological identification
of radiation-chimaeras. Nature 1956; 177: 452-454.
4. Main JM, Prehn RT. Successful skin homografts after the administration
of high dosage X radiation and homologous bone marrow. J Natl
Cancer Inst 1955; 15: 1023-1029.
5. Thomas ED, Storb R, Clift RA, Fefer A, Johnson FL, Neiman PE et al.
Bone-marrow transplantation. N Engl J Med 1975; 292: 832-843,
895-902.
6. Burchenal JH, Oettgen HF, Holmberg EAD, Hemphill SC, Reppert JA.
Effect of total body irradiation on the transplantability of mouse leukemias.
Cancer Res 1960; 20: 425.
7. Barnes DWH, Loutit JF. Treatment of murine leukaemia with x-rays and
homologous bone marrow: II. Br J Haematol 1957; 3: 241-252.
8. Mathe G, Amiel JL, Schwarzenberg L, Catton A, Schneider M. Adoptive
immunotherapy of acute leukemia: Experimental and clinical results.
Cancer Res 1965; 25: 1525-1531.
9. Weiden PL, Flournoy N, Thomas ED, Prentice R, Fefer A, Buckner CD et
al. Antileukemic effect of graft-versus-host disease in human recipients
of allogeneic-marrow grafts. N Engl J Med 1979; 300: 1068-1073.
10. Weiden PL, Sullivan KM, Flournoy N, Storb R, Thomas ED, and the Seattle
Marrow Transplant Team. Antileukemic effect of chronic graft-versus-host
disease. Contribution to improved survival after allogeneic marrow
transplantation. N Engl J Med 1981; 304: 1529-1533.
11. Kolb HJ, Mittermüller J, Clemm Ch, Holler G, Ledderose G, Brehm G
et al. Donor leukocyte transfusions for treatment of recurrent chronic
myelogenous leukemia in marrow transplant patients. Blood 1990;
76: 2462-2465.
12. Kolb HJ, Schattenberg A, Goldman JM, Hertenstein B, Jacobsen N, Arcese
W et al. Graft-versus-leukemia effect of donor lymphocyte transfusions
in marrow grafted patients. European Group for Blood and Marrow
Transplantation Working Party Chronic Leukemia. Blood 1995;
86: 2041-2050.
13. Yu C, Storb R, Mathey B, Deeg HJ, Schuening FG, Graham TC et al.
DLA-identical bone marrow grafts after low-dose total body irradiation:
Effects of high-dose corticosteroids and cyclosporine on engraftment.
Blood 1995; 86: 4376-4381.
14. Storb R, Yu C, Wagner JL, Deeg HJ, Nash RA, Kiem H-P et al. Stable
mixed hematopoietic chimerism in DLA-identical littermate dogs given
sublethal total body irradiation before and pharmacological immunosuppression
after marrow transplantation. Blood 1997; 89:
3048-3054.
15. Storb R, Yu C, Barnett T, Wagner JL, Deeg HJ, Nash RA et al. Stable
mixed hematopoietic chimerism in dog leukocyte antigen-identical littermate
dogs given lymph node irradiation before and pharmacologic
immunosuppression after marrow transplantation. Blood 1999; 94:
1131-1136.
16. Storb R, Yu C, Zaucha JM, Deeg HJ, Georges G, Kiem H-P et al. Stable
mixed hematopoietic chimerism in dogs given donor antigen, CTLA4Ig,
and 100 cGy total body irradiation before and pharmacologic immunosuppression
after marrow transplant. Blood 1999; 94: 2523-2529.
17. Storb R, Yu C, McSweeney P. Mixed chimerism after transplantation of
allogeneic hematopoietic cells. In: Thomas ED, Blume KG, Forman SJ,
eds. Hematopoietic Cell Transplantation, 2nd Edition. Boston: Blackwell
Science, 1999: 287-295.
18. Storb R. Nonmyeloablative preparative regimens: experimental data
and clinical practice. In: Perry MC, ed. ASCO Education Book 1999:
241-249.
19. Woolfrey AE, Nash RA, Frangoul HA, McSweeney PA, Sanders JE, Ochs
HD et al. Non-myeloablative transplant regimen used for induction of
multi-lineage allogeneic.
20. Yu C, Nash R, Lothrop C, Zaucha J, Storb R. Severe canine hereditary
hemolytic anemia treated by marrow grafts using nonmyeloablative immunosuppression.
Blood 1998; 92 (Suppl 1): 263a, #1078. Abstract.
21. McSweeney PA, Wagner JL, Maloney DG, Radich J, Shizuru J, Bensinger
WI et al. Outpatient PBSC allografts using immunosuppression
with low-dose TBI before, and cyclosporine (CSP) and mycophenolate
mofetil (MMF) after transplant. Blood 1998; 92 (Suppl 1): 519a,
#2133. Abstract.