Universidade Federal de São Paulo, São Paulo, BrazilHosp Santa Marcelina, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Fermino, Fabiana Aidar

Oliveira, José Salvador Rodrigues de

Biology of Blood and Marrow Transplantation

English

Universidade Federal de São Paulo, São Paulo, BrazilHosp Santa Marcelina, São Paulo, BrazilUniversidade Federal de São Paulo, EPM, São Paulo, BrazilWeb of Scienc

Fermino, Fabiana Aidar [UNIFESP]

Oliveira, José Salvador Rodrigues de [UNIFESP]

Repositório Institucional UNIFESP

data also suggest that permanent alopecia can be seen with non-busulfan containing regimens. One important observation was pa-tients usually accept permanent alopecia as the price for the cure andfind ways to hide it unless they are questioned about. This may beresponsible for underestimation of the true incidence of permanentalopecia after HDC. Our findings may also have medico legal andpsychosocial implications that need to be taken into considerationwhen consenting patients for HSCT.134NO EVIDENCE FOR INCREASED TRANSPLANT RELATED TOXICITY INPH CHRONIC MYELOGENOUS LEUKEMIA (CML) AND ACUTE LYM-PHOBLASTIC LEUKEMIA (ALL) WITH PRIOR EXPOSURE TO DASATINIBLeiba, M.1, Shimoni, A.1, Guilhot, F.2, Martineau, G.2, Renaud, M.2,Francois, S.2, Hardan, I.1, Nagler, A.1 1Chaim Sheba Medical Center,Tel Hashomer, Israel; 2Oncology Hematology and Cell Therapy CHU LaMiletrie, Poitiers, France.SCT is frequently used as salvage or curative therapy in patients(pts) with advanced CML or Ph ALL previously treated with Ima-tinib. While one study showed higher incidence of GVHD, VOD andTRM, most studies have demonstrated that Imatinib therapy prior toSCT does not adversely affect SCT outcome. Dasatinib is a SRC/ABL kinase inhibitor currently being used in pts with Imatinib-resistant. Most of these pts will eventually undergo SCT, raising thequestion of whether Dasatinib therapy may adversely affect SCToutcome. We report eight pts: CML – 6 (CP1-4, low sokal score –3,high sokal score –1, CP2-1, AP-1) and Ph ALL –2 who receivedDasatinib prior to alloSCT (n7) or autoSCT (n1). Donors werematched siblings –4 or unrelated –2 or mismatch related (haploSCT)–1. 5 were male and 3 female with a median age of 46.5 (16-56) years.First line therapies included Hydroxyurea & Interferon or chemo-therapy followed by Imatinib for the CP CML and advanced CML/Ph ALL pts, respectively. All pts subsequently received Dasatinib70mg x 2/day due to resistance to Imatinib, resulting in completehematological response in all, as well as complete (n5) or partialcytogenetic response (CyR) (n2) prior to SCT. One pt did notachieve CyR prior to SCT. The pts were conditioned with either amyeloablative (n5) or a reduced intensity protocol (n3). GVHDprophylaxis consisted of CSA and MTX (n6) or complete T-celldepletion (n1). Pts received a mobilized peripheral blood stem cellgraft with 11.4–19.8  106 CD34 cells/ kg. The pt who underwentautoSCT was successfully mobilized (2 apheresis cycles yielding 5.7 106 CD34/kg). Dasatinib was stopped 6 days before mobilization.All pts engrafted reaching ANC  0.5109/L on day 14 (11-21)and PLT 20109/L on day 12.5 (11-17). Chimerism was 99.4 –100%. Transplant related toxicities were minimal. Only 1 pt devel-oped severe mucositis. No pt developed hyperbilirubinemia or VOD.There was no increased risk of infections. Acute GVHD (Gr II) wasobserved in only 1 pt, while 2 developed extensive chronic GVHD.With a median followup of 8.5 (2-13) months, 6 pts are alive, 5 in CR,while 2 died of disease progression. We may conclude that in ptsundergoing SCT following Dasatinib there is no evidence that Da-satinib adversely affect post SCT outcome as no increased transplantrelated organ toxicities, non-engraftment, GVHD or infections wereobserved. Larger studies are obviously indicated to confirm our pre-liminary results.135ONCE-DAILY ADMINISTRATION OF MODIFIED-RELEASE TACROLIMUSCAPSULE (MR) FOR THE PROPHYLAXIS OF GRAFT-VERSUS-HOST-DIS-EASE (GVHD) AFTER UNRELATED DONOR BONE MARROW TRANS-PLANTATION (BMT)Okamoto, S.1, Gondo, H.2, Imamura, M.3, Kodera, Y.4 1Keio UniversityHospital, Tokyo, Japan; 2Saga Prefectural Hospital Koseikan, Saga,Japan; 3Hokkaido University Hospital, Sapporo, Japan; 4Japanese RedCross Nagoya First Hospital, Nagoya, Japan.The safety and efficacy profiles of tacrolimus capsule, twice-daily(BID) administration of Prograf® (PRG), in patients received al-logeneic stem cell transplantation are well defined. MR is anextended-release formulation of tacrolimus which is administeredonce-daily (QD). QD dosing regimen could improve complianceand convenience while maintaining the potency of immune sup-pression. Studies in renal and liver transplantation indicated thatthe MR formulation given QD and PRG administered BIDshowed a similar exposure (AUC0-24) and correlation betweenAUC0-24 and Cmin.We here report the efficacy, safety and pharmacokinetics (PK) ofMR in patients who underwent allogeneic BMT from HLA-matched unrelated donors. PRG was started as continuous i.v. at adose of 0.03mg/kg from 1 to 3 days before BMT, MTX was alsogiven on days 1, 3 and 6. The infusion of tacrolimus was switchedto QD oral administration of MR 38.0 days (24-87 days) afterBMT. The blood sampling for PK was collected 8-60 days afteradministration of MR. A total of 20 patients received BMT, and 15of them received MR. The diagnosis included AML (3), CML(3),MDS (3), ML (2), ATL (1), CNL (1), Waldenstrom’s Macroglob-ulinemia (1) and Myelofibrosis (1). All 15 patients received TBI,together with cyclophosphamide (13), or cytarabine (1), or mel-phalan (1) as conditioning. Acute GVHD was graded according tothe modified Gluksberg grading system.Before day 100 post-BMT, 7 of 15 (46.7%) patients developedgrade II-IV acute GVHD, and 3 (20.0%) developed grade III-IVacute GVHD. Three patients developed grade II-IV acute GVHD(2 grade II and 1 grade III) after conversion to MR. At one yearpost-BMT, cumulative incidence of chronic GVHD was 51.0%,and the cumulative overall survival rate was 93.3%. All adversedrug reactions observed during the administration of MR werealready known as those of PRG. PK profile of MR was evaluated in13 patients. AUC0-24 and Cmin were 217.56100.01 ng.h/mL and6.032.65 ng/mL, respectively. Co-efficiency between AUC0-24and Cmin was highly correlated (r0.8679) as studies in renal andliver transplantation.These results suggest that QD administration of MR is effectiveas an alternative to BID administration of PRG capsule for theprophylaxis of acute and chronic GVHD in unrelated donor BMT.Ongoing studies are aiming to evaluate the relapse and survivalrates over one year in BMT as well as the long-term benefits of MRin multiple types of organ transplantation.136LATE-ONSET NONINFECTIOUS PULMONARY COMPLICATIONS AFTERALLOGENEIC BONE MARROW TRANSPLANTATION IN BRAZIL: INCI-DENCE, CLINICAL FEATURES AND INFLUENCE OF TUBERCULOSISFermino, F.A.1, Oliveira, J.S.R.1,2 1Universidade Federal de Sao Paulo,Sao Paulo, Brazil; 2Hospital Santa Marcelina, São Paulo, Brazil.Despite advances in the management of bone marrow transplanta-tion (BMT), pulmonary complications have been developed in 40-60% of patients, influencing morbidity and mortalitality. Late-onsetnoninfectious pulmonary complications (LONIPC) include a numberof different entities and an association with chronic graft-versus-hostdisease (GVHD) has been noted for almost all of them. Among 253patients who underwent allogeneic BMT at Universidade Federal deSão Paulo and Hospital Santa Marcelina, 159 of them survived at least6 months, 16 (10%) fulfilled the diagnostic criteria of LONIPC.There was a significant association between pulmonary infectious(p0,01), acute and chronic GVHD and the development of LO-NIPC (p0,038 and 0,043, respectively). The frequency of Tubercu-losis (Tb) among our patients was 3,7%. Two patients with previousTb fulfilled criteria for LONIPC. We believe that the pulmonarysymptoms and lung function tests presented by our patients can beattributed to Tb sequelae. However, it was not possible to excludeLONIPC since biopsy was not performed. On the other hand, it isnecessary to determine if in Brazil and other endemic areas of Tb, thepulmonary biopsy can provide the correct diagnosis in similar cases. Inview of theses findings, we conclude that the LONIPC is an impor-tant complication after allogenic BMT, chronic and acute GVHD issignificantly associated with this complication and Tb sequelae can bea differential diagnosis with LONIPC mainly in endemic areas. Theseresults have implications for the care of pacients who developedrespiratory symptoms after BMT.Poster Session I 51

Late-onset noninfectious pulmonary complications after allogeneic bone marrow transplantation in Brazil: Incidence, clinical features and influence of tuberculosis

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Late-onset noninfectious pulmonary complications after allogeneic bone marrow transplantation in Brazil: Incidence, clinical features and influence of tuberculosis

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