Bitencourt, M.

Bonfim, C.

Doro, M.

Funke, V.

Medeiros, C.R.

Pasquini, R.

Ruiz, J.

Setubal, D.

Zanis-Neto, J.

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106 transplanted unilaterally) and single positive RT1n (4.5  106
to 9.0 106) and RT1a (6.0 106 to 12.0 106) cells transplanted
bilaterally to naive Lewis rat. Donor-speciﬁc chimerism (for MHC
class I antigens) and efﬁcacy of MACS sorting was assessed by ﬂow
cytometry. Therapeutic effect of adoptive transfer of donor chi-
meric cells was evaluated following bilateral transplantation of skin
ﬂaps of donor origin (LBN and ACI). Results: In primary trimeras
13.1% of LBN donor positive cells (RT1n) and 6.8% of ACI donor
positive cells (RT1a) was found. MACS-sorting revealed 87%-96%
purity of double positive RT1n/RT1a cells. At day 21 secondary
trimera created via double positive cell transplantation (RT1n/
RT1a) revealed 8.3% of RT1n and 11.3% of RT1a positive cells,
whereas injection of single positive cells (RT1n and RT1a) resulted
in 6.0% of RT1n and 7.6% of RT1a chimerism. Prolonged skin ﬂap
survival was achieved over 84 days after double positive RT1n/
RT1a transplant and over 120 days in single positive chimeric cells
recipients (still under observation). Conclusions: Intraosseous
transplantation of bone marrow from two different MHC mis-
matched donors under a 7-day 
-TCRmAb/CsA protocol re-
sulted in creation of donor-speciﬁc trimera. Isolation and adoptive
transfer of chimeric cells proved to be efﬁcacious in extension of
donors skin ﬂap survival without prolonged immunosuppression.
70
BONE MARROW TRANSPLANTATION (BMT) FOR HEAVILY TRANS-
FUSED PATIENTS (pts) WITH SEVERE APLASTIC ANEMIA (SAA): 147
PTS TREATED AT THE SAME INSTITUTION WITH BUSULFAN (BU) 
CYCLOPHOSPHAMIDE (CY)
Bonﬁm, C., Bitencourt, M., Funke, V., Setubal, D., Ruiz, J., Doro, M.,
Medeiros, C.R., Zanis-Neto, J., Pasquini, R. Federal University of
Parana, Curitiba, PR, Brazil.
BMT from HLA identical siblings is currently the best treatment
for young pts with SAA. However, heavily transfused pts have an
inferior survival due to an increased risk of rejection and transplant
related mortality (TRM). In developing countries not only the
number but the quality of pretransplant transfusions should be
considered because most of them are not ﬁltered or irradiated. In
1993 we introduced BU to the preparatory regimen of pts with
more than 15 pretransplant transfusions trying to reduce the ele-
vated incidence of rejection observed in pts receiving only CY. In
this study we retrospectively analyzed the results in 147 pts trans-
planted between 01/93-01/05 with BU  CY. Age: 2-46 y (M: 19).
Previous blood transfusions: 15-675 (M: 34 UI). Disease duration:
1-114 mo (M: 4). All pts received bone marrow from HLA iden-
tical siblings. Preparatory regimen: BU 12 mg/kgCY 120 mg/kg.
GVHD prophylaxis: cyclosporine  methotrexate. TNC infused:
1.17-6.55  108/kg (M: 3.01). Immediately prior to BMT, 39 pts
(26%) had active bacterial or fungal infections. One hundred and
four pts are alive with a median follow up of 2719 days (range:
189-4506). Eight pts died before day 28 and were not evaluable
for engraftment. Primary graft failure (GF) occurred in 4/139 pts
(2.8%) and all pts died. Late GF occurred in 19/135 pts (14%)
between 207-1448 days after BMT (M: 584 days). 10/19 pts are
alive (5 after a 2nd BMT and 5 after treatment with immune
suppression). Mucositis grade III-IV occurred in 80 pts (54%).
VOD: 2 pts. Hemorrhagic cystitis: 13 pts (8.8%). Acute GVHD
grade II-IV: 20/135 pts (III-IV: 11 pts—8%). Chronic GVHD:
22/128 pts (extensive: 16 pts—12.5%). Forty-three pts died be-
tween 10-3072 days after BMT (M: 154 days). Death was mainly
related to infections or bleeding. 17 pts died before day 100 and
76% of them had severe infections prior to transplant. 11/16 pts
with extensive chronic GVHD died. Pts with more than 50 previ-
ous blood transfusions had an inferior survival when compared to
those receiving between 15-50 UI (54%  74%; P  .005). 28 pts
are surviving more than 10 y after BMT with a satisfactory quality
of life. We conclude that the use of BU  CY reduced the risk of
rejection in this group of pts. Survival reached 70% in pts receiving
between 15-50 transfusions. Alternative preparatory regimens
could be offered to pts receiving 	50 UI before transplant. Infec-
tions immediately prior to conditioning increased the risk of TRM.
71
THERAPEUTIC ANTI-TUMOR IMMUNITY MEDIATED BY TRANSIENTLY
ENGRAFTING ALLOGENEIC LYMPHOCYTES: THE “ALLOGENEIC EF-
FECT” REVISITED
Symons, H.J., Levy, M.Y., Wang, J., Zhou, X., Fuchs, E.J. Sidney
Kimmel Comprehensive Cancer Center, Baltimore, MD.
The “allogeneic effect” refers to the induction of host B cell
antibody synthesis or host T cell cytotoxicity, including tumori-
cidal activity, by an infusion of allogeneic lymphocytes. We have
previously shown that treatment of mice with cyclophosphamide
(Cy) followed by infusion of CD8 T cell-depleted allogeneic
spleen cells (Cy  CD8 DLI) induces anti-tumor activity in a
model of minimal residual leukemia, even though the donor cells
are eventually rejected by the host immune system. The purpose of
the current investigation was to test the activity of Cy  CD8
DLI in the treatment of well-established cancer, and to character-
ize the mechanisms of the anti-tumor effect. BALB/c mice were
inoculated intravenously (IV) with the syngeneic A20 lymphoma/
leukemia or the RENCA renal cell carcinoma on day 0 and were
then treated with nothing, Cy alone on day 14, or Cy  CD8
DLI from MHC-mismatched C57BL/6 donors on day 15. In both
tumor models, the combination of Cy  CD8 DLI signiﬁcantly
prolonged survival compared to mice treated with nothing or with
Cy alone. While depletion of CD4 T cells from the DLI signif-
icantly diminished the beneﬁcial effect of CD8 DLI, puriﬁed
CD4 T cells alone were inactive, demonstrating that donor
CD4 T cells and another population of cells were required for
optimal anti-tumor activity. Several observations pointed to an
active role for the host immune system in the anti-tumor activity of
CyCD8DLI. First, host T cells participated in the anti-tumor
effect of treatment with Cy alone, since the drug’s activity was
diminished in tumor-bearing scid mice or in normal BALB/c mice
depleted of T cells. Second, while Cy  CD8 DLI caused no
GVHD in tumor-bearing but immunocompetent BALB/c recipi-
ents, it caused fatal acute GVHD in either tumor-bearing scid or
T-cell depleted BALB/c mice. Finally, the anti-tumor effect of Cy
and Cy  CD8 DLI was also signiﬁcantly inhibited in BALB/c
mice depleted of CD8 T cells. These results demonstrate that
transiently engrafting T cells administered after Cy can induce
signiﬁcant anti-tumor effects against solid and liquid tumors. We
propose that upon recognition of alloantigen on host antigen-
presenting cells (APCs), allogeneic donor CD4 T cells deliver
activating ligands to the APCs, thereby generating effective “help”
to break tolerance in tumor-speciﬁc host CD8 T cells. This
mechanism may correspond to the “allogeneic effect” in the anti-
tumor response described over three decades ago.
72
TREATMENT OF MYELODYSPLASTIC SYNDROMES WITH ALLOGENEIC
HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT)—IMPACT OF
NON-RELAPSE MORTALITY ON OUTCOMES
Ativitavas, T.1, Saliba, R.2, Sergio, G.2, Ghosh, S.2, Champlin, R.2,
de Lima, M.2 1Mahido University, Bangkok, Thailand; 2Department of
Blood and Marrow Transplantation, Houston, TX.
Introduction: Myelodysplastic syndromes (MDS) are clonal he-
matopoietic disorders potentially curable with allogeneic HSCT.
Non-relapse mortality (NRM) is a major cause of treatment failure
in this context. Preparative regimens may impact survival (S) dif-
ferently given dissimilar toxicity rates. We investigated this hy-
pothesis in a dataset of patients with MDS (as deﬁned by WHO
criteria) treated in our institution from January 1993-December
2004.Methods:We reviewed 88 patients (65% males); 30 patients
(34%) received induction chemotherapy prior to HSCT (4 RA, 4
RARS, and 22 RAEB) and 58 patients (66%) did not (30 RA, 3
RARS, 21 RAEB, and 4 refractory cytopenia). Median age was 50
years (20-69). IPSS was high risk in 27%, intermediate 2 in 40%,
intermediate 1 in 28%, and low in 5%. Cytogenetics were poor in
52%, intermediate in 17% and good in 31% of patients. 53 patients
(60%) were treated with myeloablative regimens including 12 Gy
TBI-based (11/53), Bu/Cy (17/53) and Bu/Flu (25/53). 35 (40%)
patients were treated with reduced intensity regimens (Flu/Mel,
FAI or low-dose busulfan/Flu). Donor was matched-related in
Poster Session I
28


Bone Marrow Transplantation (BMT) for heavily Transfused Patients (pts) with Severe Aplastic Anemia (SAA): 147 pts treated at the same institution with Busulfan (BU) + Cyclophosphamide (CY) 

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Bone Marrow Transplantation (BMT) for heavily Transfused Patients (pts) with Severe Aplastic Anemia (SAA): 147 pts treated at the same institution with Busulfan (BU) + Cyclophosphamide (CY)

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