ALBERT

Description: Abstract 2291 Poster Board II-268 Haploidentical bone marrow transplantation (BMT) is an alternative treatment to patients with high-risk hematologic malignancy lacking a HLA-matched donor and those urgently need transplantation. We used a haploidentical-BMT protocol without ex vivo T cell depleted based on the knowledge that marrow grafts have 10 times fewer lymphocytes compared to peripheral blood stem cell grafts and granulocyte colony-stimulating factor (G-CSF) donor priming reduce the incidence of acute GvHD. Materials and Methods: 40 patients (median age of 32, 12-63) with advanced disease or leukemia with poor prognostic features underwent unmanipulated haplo-BMT: 22 with AML, 9 with ALL, 3 with CML, 3 with Hodgkin lymphoma and 3 with plasmacell leukemia. Status at disease: 22 early (first or second comple! te remission), 18 advanced (progressive or refractory disease). All pairs of donors and recipients were identical for one HLA haplotype and incompatible at 2 or 3 loci.The myeloablative conditioning regimens used were different; antithymocyte globuline, cyclosporine, metotrexate, mycophenolate mofetil and basiliximab were used for GvHD prophylaxis. Donors were primed with filgrastim at 4 micrograms/Kg/d for 7 consecutive days. Bone marrow cells were harvest on the 8 day and were infused unmanipulated. Results: the median dose of total nucleated, CD34+ and CD3+cells was 7×10e8/Kg (1.01-28.7), 2.3×10e6/Kg (1.17-6.0) and 23.3×10e6/Kg (9.7-66.6) respectively. 1 patients had a primary graft failure and 5 patients died early prior to engraftment. In the remaining 34 patients, engraftment was seen with median time to granulocyte and platelet recovery of 22 and 27 days respectively; acute GvHD was grade 0 in 17 patients (50%), grade I in 9 (26%), grade II in 7 (20%) and grade IV in 1 (3%). In 29 evaluable patients, chronic GvHD was limited in 3 (10%) and extensive in 1 (3%). Transplant-related mortality at 6 months for early and advantage stage was 22% and 35% respectively. After a median follow up of 18 (3-42) months, 8 patients relapsed; 11 patients (50%) in the early stage and 4 (22%) in advanced phase are now living in haematological remission. The 1-year Kaplan-Meyer probability of disease-free survival is 45% for all patients. Conclusion: the high engraftment rate, low incidence of grade II-IV acute GvHD and an acceptable TRM suggest that G-CSF-primed marrow grafting along with sequential immunosuppression could provide an excellent alternative for patients who lack matched donors. Disclosures: No relevant conflicts of interest to declare.

Description: We evaluated the impact of World Health Organization (WHO) classification and WHO classification–based Prognostic Scoring System (WPSS) on the outcome of patients with myelodysplastic syndrome (MDS) who underwent allogeneic stem cell transplantation (allo-SCT) between 1990 and 2006. Five-year overall survival (OS) was 80% in refractory anemias, 57% in refractory cytopenias, 51% in refractory anemia with excess blasts 1 (RAEB-1), 28% in RAEB-2, and 25% in acute leukemia from MDS (P = .001). Five-year probability of relapse was 9%, 22%, 24%, 56%, and 53%, respectively (P 〈 .001). Five-year transplant-related mortality (TRM) was 14%, 39%, 38%, 34%, and 44%, respectively (P = .24). In multivariate analysis, WHO classification showed a significant effect on OS (P = .017) and probability of relapse (P = .01); transfusion dependency was associated with a reduced OS (P = .01) and increased TRM (P = .037), whereas WPSS showed a prognostic significance on both OS (P = .001) and probability of relapse (P 〈 .001). In patients without excess blasts, multilineage dysplasia and transfusion dependency affected OS (P = .001 and P = .009, respectively), and were associated with an increased TRM (P = .013 and P = .031, respectively). In these patients, WPSS identified 2 groups with different OS and TRM. These data suggest that WHO classification and WPSS have a relevant prognostic value in posttransplantation outcome of MDS patients.

Description: Abstract 1195 Poster Board I-217 The policy of the Rome Transplant Network (RTN), a metropolitan network of transplant Centers, for patients candidates to an allogeneic hematopoietic stem cell transplant (HSCT) and lacking an HLA identical sibling is the contemporary search for one the HSC alternative sources such as Matched Unrelated Donor (MUD),Cord Blood Unit (CBU) or Haploidentical Related Donor (HRD). The main aim of the RTN policy is the identification of a suitable donor in order to perform transplant in adequate timing. The selection criteria for MUD consist of a 8/8 HLA loci matching tested at low resolution for class I HLA and at high resolution (HR) for class II; one difference in C Ag is considered acceptable in case of both I and II class HR identity. CBU's selection criteria are instead based on cell doses (TNC≥2.5×107/kg and CD34+≥1× 105/kg) and on a HLA-compatibility ≥to 4/6 HLA Ag. From April 2006, the haplodentical option was also simultaneously considered, so all closer family members have been tested for the HLA. Here, we report the results of the intention to treat (ITT) analysis on the potential therapeutic impact of our transplant policy. Data were obtained from RTN database. From April 2006 to date, 196 pts have been candidated to receive an allogeneic HSCT for hematological disease. Sixty-six out of 196 (34%) underwent HSCT from HLA identical sibling, while a search process for an alternative donor was activated for 130 pts. Of 130 pts, 9 (7%) lost the eligibility to transplant early during the search process and 19 (15%) died of early disease progression in most cases: a suitable MUD or CBU had been identified for 13 of 19 within 3 months from the start of the search and only 6 pts (5%) died without an alternative donor had been found. To date, 73/102 evaluable pts (72%) lacking an HLA identical sibling have been transplanted (n=66: 23 MUD; 24 CBU; 19 HRD) or are willing to proceed towards the transplant (n=7: 3 MUD;2 CBU; 2 HRD). In summary, for all 196 candidates to an allogeneic transplant the eligibility was confirmed for 187 (95%), a suitable donor could be identified for 181 (92%) of all pts or 97% of the eligible ones and an allogeneic transplant could be performed for 168 (86%) of all candidates or 93% of those eligible. From this ITT analysis, we can conclude that, by adopting the RTN policy of widespread donor search and multiple transplant options, the allogeneic transplant can be offered as potential therapeutic procedure to a large majority of pts. Disclosures: No relevant conflicts of interest to declare.

Description: WHO classification and WPSS score (JCO2007;25:3503) have been recently proved to have prognostic significance in myelodysplastic syndromes (MDS), but their impact on the outcome of patients (pts) receiving allogeneic stem-cell transplantation (allo-SCT) is still to be clarified. We retrospectively evaluated the prognostic value of WHO classification and WPSS at the time of transplant in 406 MDS pts who underwent allo-SCT between 1990 and 2006. Patients were reclassified according to the WHO criteria: 30 had refractory anemia (RA/RARS), 54 refractory cytopenia (RCMD/RS), 51 RA with excess blasts (RAEB), type 1 and 95 RAEB type 2. One hundred twenty-seven pts were classified as acute myeloid leukemia (AML). The median recipient age was 48 years (range 17–67). There were 281 HLA-matched sibling and 125 unrelated donor SCT. One hundred forty-three pts (35%) received a reduced intensity regimen (RIC). Considering WHO categories, the probability of OS at 5-years was 0.8 in RA/RARS, 0.52 in RCMD/RS, 0.48 in RAEB-1, 0.26 in RAEB-2 and 0.29 in AML, while the probability of RFS at 5-years was 0.92, 0.78, 0.74, 0.47 and 0.44 respectively. The cumulative probability of TRM was 0.43. We performed a Cox analysis with WHO category, cytogenetics, transfusion dependency, recipient age, disease status, type of donor and type of conditioning as covariates. WHO classification had a significant effect on both OS (P=0.017), and RFS (P=0.01). Cytogenetic risk significantly affected RFS (P=0.04), while had a borderline effect on OS (P=0.09). A regular transfusion dependency before SCT was associated with a reduced OS (P=0.01) and increased TRM (P=0.037), while no significant effect on RFS was noticed. Age and stage of the disease at transplant showed a significant effect on OS (P=0.02 and P=0.04, respectively). RIC and active disease at transplant were associated to a reduced probability of RFS (P=0.02 and P=0.017 respectively). Age and use of myeloablative conditioning were significant risk factors for TRM (P=0.018 and P=0.032 respectively). The WPSS score, based on MDS-WHO category, cytogenetics and transfusion dependency at the time of SCT, was calculated for 171 pts. WPSS showed a prognostic significance on both OS and RFS in a Cox analysis with age of recipient, disease status, type of donor and type of conditioning as covariates (P=0.02 and P=0.01). Focusing the analysis on 84 MDS pts without excess blasts, multilineage dysplasia and regular transfusion-dependency significantly affected post-transplant OS (P=0.005 and P=0.009, respectively), and were associated to an increased TRM. In this clinical setting, WPSS allowed to identify 2 major groups of pts (very-low/low vs. intermediate risk) with significant different OS and TRM (P=0.013 and P=0.039). In conclusion, these data show that WHO classification and WPSS have a relevant prognostic value for the post-transplantation outcome of MDS pts and should be taken into account in transplantation decision-making, especially in subjects with less advanced disease. The independent negative effect of transfusion dependency strengthens the rationale to examine the consequences of iron overload and the potential benefit of chelation therapy in MDS transplant setting.