ALBERT

Description: Abstract 4478 Allogeneic stem cell transplantation (AlloSCT) is the treatment of choice in advanced chronic myelogenous leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL). However, post transplant relapse rate is high and outcome is often poor in this setting. Reduction of tumor mass pre-transplant and maintenance therapy post alloSCT, may improve response rate and reduce relapse rate. We speculated that the second-generation tyrosine-kinase inhibitor (TKI) Nilotinib (Tasigna, Novartis Pharmaceuticals) would be effective in achieving these goals. In the current study Nilotinib, was administered as maintenance therapy post alloSCT in patients (pts) with advanced CML and Ph+ ALL (study CAMN107AIL03T). However, TKIs have been demonstrated in previously published literature to affect T cells proliferation and signal transduction and to potentiate LGL and NK cell activity. Furthermore, in recent studies TKIs have also been demonstrated to ameliorate chronic GVHD. We therefore assessed immunological reconstitution and function including flow analysis of lymphocyte subsets, T-mitogenic response to αCD3 and PHA, thymic activity as determined by the quantification of the T cell receptor excision circles (TREC), TCR repertoire and NK cells cytotoxic activity against K562 cell line. In all, the study included 24 pts. Patients engrafted in a median day +15 (range, 10–38) with 100% donor chimerism. Acute GVHD grade 3/4 was reported in 3 pts (14%) and the rate of extensive chronic GVHD at last follow up was 50%. At 6 months after alloSCT, 11 of 15 pts with advanced CML had attained CCyR, 11 of 15 pts with advanced CML had attained a MMR or better, and 5 of 7 pts with Ph+ ALL attained a CR. The median OS was 16 months, with predicted 1- and 2- year rates of 55% (95% CI, 32% – 72%) and 50% (95% CI, 28% – 68%), respectively. The median PFS was 11 months, with predicted 1- and 2- year rates of 50% (95% CI, 28% – 68%) and 38% (95% CI, 17% – 59%), respectively. Immunological testing was performed pre- and post Nilotinib maintenance therapy in 12 pts (advanced CML-8, Ph+ ALL-4) who received Nilotinib for at least 90 days following alloSCT. The median age was 34.5 years (range, 21–57) and 75% were males. Six pts underwent alloSCT from an HLA-matched sibling donor, 4 from matched unrelated and 2 from an alternative donor (cord blood-1, haploidentical-1). All had myeloablative conditioning. GVHD prophylaxis included CSA and MMF. The relative percentage of T- lymphocyte subsets (assessed by FACS) and total lymphocytes number were stable during Nilotinib maintenance administration after alloSCT, while a 7.8±2.5 fold increase in B cells was noted. T cell mitogenic response with αCD3 and PHA (stimulation index ratio) was sustained (2.5±1.0, vs. 2.8±1.05 and 3.3±1.3 vs. 5.3±2.9 stimulation, pre- and post Nilotinib therapy, respectively). Mean thymic output determined by TREC quantification pre-, during and post Nilotinib administration was 81.8±108, 81.2±90.3 and 142.8±197.4 copies per 0.5ug DNA indicating continuous thymopoiesis. Similarly, no significant change of the TCR repertoire was observed during Nilotinib treatment. Specifically, normal expression of the TCR repertoire was detected in 15.1±5.5 and 15.3±5.6 of the examined TCRs, clonal expression was detected in 2.5±2.2 and 2.9±3 of the examined receptors, while reduced expression was detected only in 6.4±4.3 and 5.8±4.5 of the examined receptors pre-and post Nilotinib treatment, respectively. NK cytotoxic activity against K562 expressed as fold of change from baseline, also remained stable during Nilotinib treatment (2.8±1.1 and 2.3±0.8, respectively). In summary, Nilotinib maintenance therapy post alloSCT in pts with advanced CML and Ph+ALL did not interfere or jeopardized immune reconstitution and function including the number of immune cell subsets, T cell mitogenic response, TCR repertoire, thymic output and NK cytolytic activity post alloSCT. Based on this immunological data we would further recommend Nilotinib maintenance therapy post alloSCT in pts with advanced CML and Ph+ALL. Disclosures: Nagler: Novartis: Honoraria, Research Funding.

Description: Abstract 518 Allogeneic stem cell transplantation (SCT) is a potentially curative therapy for patients (pts) with AML and MDS. SCT is associated with substantial mortality during the first 2 years after treatment due to relapse and non-relapse causes, whereas after 2 years survival curves often reach a plateau. However, late mortality and late events continue to cause treatment failures through the late post-transplant course. The pattern of late events has been reported following myeloablative conditioning (MAC) but is not well defined in the RIC setting. To explore late outcomes we retrospectively analyzed SCT results in a cohort of 298 pts with AML/MDS given allogeneic SCT with various regimens. As a general role, pts meeting standard eligibility criteria were given MAC, consisting of high dose intravenous busulfan (Bu) and cyclophosphamide (BuCy). Pts considered at excessive risk for non-relapse mortality (NRM), mostly due to advanced age, were given a reduced toxicity regimen such as fludarabine with high-dose Bu (FB4) or treosulfan (FT) or a RIC regimen of fludarabine and reduced doses of Bu (FB2). The 2-year and 5-year overall survival (OS) for this cohort was 48% (95CI, 42-54) and 38% (95CI, 31-44), respectively. We identified 93 pts who were alive and leukemia-free 2 years after SCT. The median age at SCT was 52 years (17-72), 52 male, 41 female. The donors were HLA-matched siblings (n=57) or unrelated donors (n=36. The conditioning regimen was FB2 (n=28), FB4 (n=21, FT (n=15) or BuCy (n=29). At the 2-year time-point, 28 pts had a history of acute GVHD, 68 had a history of chronic GVHD, 43 had active chronic GVHD which still required immune suppressive therapy (IST) in 37. Among pts surviving leukemia-free 2 years after SCT, the probability of remaining alive and leukemia-free, for the next 5 years, was 81% (95CI, 71-91) and 79% (95CI, 69-88), respectively. The probability of OS was 75%, 84%, 92% and 79%, after the various regimens, respectively (p=NS). There were 14 deaths beyond 2 years, 8 deaths due to relapse and 6 due to NRM. NRM included 3 deaths due to solid cancers, 2 due to breast cancer (both in pts transplanted for therapy related AML relapsing with the primary malignancy) and one due to colon cancer. There were 3 additional secondary cancers; breast cancer, squamous cell skin cancer and Kaposi sarcoma (1 pt each; all currently alive). Two pts died of myocardial infarction and one of chronic GVHD. In all, the cumulative incidence of late NRM was 10% (4-24). Interestingly, unlike the early post-transplant period, with current supportive care regimens, late deaths from GVHD and infections are rare. Twelve pts relapsed, 24-59 months after SCT, cumulative incidence 12% (6-23); 8 died, 4 are alive following further therapies, 3 long-term. The kinetics of late relapses was similar with MAC and RIC. Advanced age (〉50) was the most significant predicting factor for shortened survival. OS was 64% and 92%, in the older and younger groups, respectively (p=0.03). All deaths due to NRM, and all secondary cancers occurred in the older group (p=0.01). Multivariate analysis (MVA) identified advanced age as the only independent predicting factor for OS; HR 3.1 (1-11.3). The conditioning regimen, disease status at SCT and donor type were not predictive. A history of acute or chronic GVHD predicted improved leukemia-free survival. Age was the most important predicting factor for NRM Active chronic GVHD was the most important factor predicting for reduced relapse risk. The cumulative probability of stopping IST by 7 years post SCT, for the entire cohort, was 73% (63-82). This probability was related to the conditioning regimen and was 80%,76%,80% and 63%, after FB2,FB4,FT and BuCy, respectively (p=0.06 for BuCy versus others). MVA identified conditioning with BuCy (HR 1.8, p=0.06) and male gender (HR 1.7, p=0.04) as predicting for prolonged need for IST. Among the 37 pts who were still on IST 2 years after SCT, the cumulative probability of stopping IST during the following 5 years was only 35%. It was higher in younger pts (59% Vs 15%, p=0.05) and in pts given FB2 (42% Vs. 31%, p=NS). In conclusion the pattern of late outcome is similar after MAC and RIC. Younger pts with AML/MDS who are leukemia-free 2 years after SCT can expect a very good outcome, while older pts are at higher risk for NRM and second cancers, which may not always relate directly to SCT. Pts given RIC are more likely to be able to stop IST, which may be associated with a better quality of life. Disclosures: No relevant conflicts of interest to declare.

Description: Allogeneic stem-cell transplantation (SCT) is potentially curative therapy in acute lymphoblastic leukemia (ALL). However, the timing of SCT during disease course and the prognostic factors for outcome are still under debate. We retrospectively analyzed all allogeneic transplants given for ALL over a 7-year period in a single institution. During this period we have used a uniform policy according to the GMALL protocols. Patients determined to be at high-risk at presentation were transplanted in the first complete remission (CR1) most often after first consolidation. Patients at standard risk at presentation were only transplanted after failure of induction or at relapse. Patients were transplanted from the best available donor and sibling donor availability was not a pre-request in any setting when referring to SCT. Patients considered eligible for myeloablative conditioning were given high-dose cyclophosphamide and TBI (12 cGy in 6 fractions). Patients considered non-eligible for myeloablative conditioning were given a reduced-intensity conditioning regimen (RIC) consisting of fludarabine and melphalan (total 140/m2). Patients with unrelated donors were also given ATG during conditioning. The study group included 81 patients, median age 40 years (range, 17–65). Immunophenotyping was B (n=31), T (n=48) and NK (n=2). Twenty-nine patients had high-risk cytogenetics [Ph+-24, t(4;11)-4, t(1;19)-1]. The donor was an HLA-matched sibling (n=48), matched unrelated (n=23), haplo-identical relative (n=8) and double umbilical cord blood (n=2). At the time of SCT, 36 patients were in high-risk CR1 (by the GMALL criteria), 12 were in CR after salvage therapy given for induction failure (CRIF), 13 patients were in CR2, and 20 patients were given SCT during active chemo-refractory disease. With a median follow-up of 27 months (range, 1–79), 31 patients are alive and 50 died (31 relapse, 19 non-relapse causes). Five patients are alive after relapse, all with isolated extra-medullary relapse (CNS-2, breast-1, bone-1, mediastinum-1). All patients with systemic relapse died of their disease. Overall and disease-free survival at 3 years were 33% (95CI, 22–44%) and 26% (95CI, 15–37%), respectively. The status of disease at SCT was the most important factor predicting for OS; the 3-year OS rates are 52%, 28%, 28% and 5% for patients transplanted in CR1, CRIF, CR2 and active disease respectively (p=0.0004). Donor type was also predicting for outcome in the univariable analysis; 3-year OS was 35%, 42% and 10% after sibling, unrelated and alternative donor transplants, respectively (p=0.04). OS rates after myeloablative conditioning and RIC were 37% and 20%, respectively (p=0.02). High-risk cytogenetics was not a risk factor for survival. Ph+ and Ph− patients had an OS of 38% and 30%, respectively, and when only analyzing patients in CR1, 48% and 53%, respectively (p=NS). Age, gender and immunophenotype were also not predicting for OS. Multivariable analysis identified two factors; SCT during CR1 was a favorable factor with HR of 0.3 (0.1–0.5, P=0.0005), while SCT with RIC was an adverse factor, HR 2.7 (1.4–5.2, P=0.004). Patients transplanted in high-risk CR1 with myeloablative conditioning had a 3-year OS of 55% (95CI, 36–75). In conclusion, best results are achieved in ALL in SCT during CR1. One can extrapolate that even better results may be expected in SCT in standard-risk ALL in CR1. Outcome after relapse and especially in chemo-refractory disease is poorer. RIC should only be used when there is an absolute contraindication for standard myeloablative conditioning.

Description: Allogeneic stem cell transplantation (SCT) is a curative therapy for patients with AML and MDS. Reduced toxicity conditioning with fludarabine and treosulfan (FT) has been shown to be a dose intensive regimen with enhanced anti-leukemia effect and acceptable toxicity. However, relapse after SCT remains the main obstacle to cure. Natural killer (NK) cell alloreactivity has a documented role in reducing relapse risk after haplotype mismatched SCT in AML. The role of NK alloreactivity in HLA matched SCT is more controversial. The missing ligand theory suggests that missing ligands in the recipient for donor inhibitor Killer immunoglobulin-like receptors (KIR) may drive NK alloreactivity after SCT in the absence of HLA mismatch. In this analysis we defined the prognostic factors for relapse and overall survival (OS) in patients with AML and MDS given FT conditioning. In particular we tested the role of recipient HLA ligands for NK KIRs in controlling relapse. The study included 203 patients with AML (n=129, 29 of them secondary to MDS or prior chemotherapy) and MDS (n=74) given SCT in 2 institutions. The median age was 58 years (range, 21–76), 126 male, 77 female. The donor was an HLA-matched sibling (n=97) or matched unrelated (n=106). Disease status was CR1 (n=65), CR2/later CR (n=24), no CR (n=44) or previously untreated MDS (n=70). Eighty patients (39%) had poor-risk cytogenetic or molecular markers. FT included treosulfan 12 gr/m2 x3 days in one institution (FT12, n=123) or 14 gr/m2 x3 in the second (FT14, n=80). 135 patients with an unrelated donor or no prior therapy were also given ATG. High-resolution HLA typing revealed that 67% expressed at least one Bw4 antigen, 81% expressed group 1 C alleles and 66% group 2 alleles. With a median follow-up of 48 months (range, 6-108 months) 86 patients are alive, 51 died of non-relapse causes (NRM) and 66 died of relapse. Seven additional patients relapsed but are currently alive. The 5-year OS and leukemia-free survival (LFS) rates were 39% (95%CI, 32-47)and 36% (95%CI, 28-43), respectively. The 5-year cumulative incidence of relapse and NRM was 38% (95%CI, 31-45) and 27% (95%CI, 31-45), respectively. The most significant predictor of relapse was the status of disease at SCT. 5-year relapse rates were 33% (95%CI, 26-42) and 55% (95%CI, 42-71) for patients in CR/untreated or refractory disease, respectively (p=0.001). Patients expressing 1-2 HLA C group 1alleles had a relapse rate of 45% (95%CI, 37-56) compared to 26% (95%CI, 13-49)in patients with missing HLA C group 1 ligand (p=0.03). Missing HLA C group 2 and/or Bw4 ligands had no effect on relapse. Multivariate analysis identified no CR at SCT (HR 3.6, p=0.001), missing HLA C group 1 ligand (HR 2.6, p=0.03), sibling donor (HR 1.8, p=0.04), poor cytogenetics (HR 1.7, p=0.05) and female donor to male recipient (HR 0.5, p=0.06) as independent factors predicting relapse. The reduced relapse rate associated with missing HLA C group 1 ligand was more pronounced in patients with MDS/secondary AML, 39% Vs 7%, respectively (p=0.02) and in patients not in CR or in untreated disease at SCT, 46% Vs. 8%, respectively (p=0.02). Missing HLA ligands were not associated with GVHD or NRM. The predicting factors for NRM were SCT beyond CR1 (HR 8.6, p=0.0002), Sibling donor (HR 0.6, p=0.08) and SCT comorbidity score 〉 2 (HR 1.8, p=0.08). The reduced relapse rate combined with no effect on NRM of missing HLA C group1 ligand translated into improved LFS, been 46% (95%CI, 27-65) compared to 30% (95%CI, 21-40) in patients expressing the ligand (p=0.07). Multivariate analysis identified SCT not in CR (HR 2.8, p=0.0007), SCT comorbidity score 〉 2 (HR 1.5, p=0.06) and missing HLA C group 1 ligand (HR 1.9, p=0.02) as independent predicting factor for LFS. In conclusion, missing HLA C group 1 ligand in SCT recipients with AML and MDS may be associated with reduced relapse risk, similar NRM and improved LFS. This effect is more pronounced in patients with MDS and secondary AML and in patients with advanced disease. The speculated mechanism is enhanced NK alloreactivity in this setting according to the missing ligand theory. These observations merit further study in larger cohorts and in patients given other conditioning regimens. They may also impact planning of immune therapies after SCT. Disclosures: No relevant conflicts of interest to declare.

Description: High-dose chemotherapy and autologous stem-cell transplantation (autoSCT) have an established therapeutic role in patients (pts) with chemosensitive relapse of aggressive lymphoma. However, autoSCT has only limited success when performed in refractory or progressive stage of the disease and in heavily pretreated or multiply relapsed pts. The expected long-term progression-free survival (PFS) in this setting is less than 20%. This study was designed to explore the safety and outcome following inclusion of Zevalin in the conditioning regimen given prior to autoSCT in pts with refractory lymphoma expected to have poor outcome with standard autoSCT. Pts with aggressive lymphoma were eligible for this study if they did not achieve CR with prior chemotherapy (either as initial treatment or after relapse) and had active disease by PET-CT. Unlike standard treatment with Zevalin, extensive marrow involvement and pancytopenia were not contraindications for therapy. The study uncluded 23 pts, median age 55 years (range, 35–66), a median of 12 months (5–129) from diagnosis. Histology was diffuse large cell (n=15), transformed low grade (n=7) and mantle cell lymphoma (n=1). Disease status was primary refractory disease (n=11) or refractory relapse (n=12). Fourteen pts had bulky disease at autoSCT. The median number of prior therapies was 3 (range, 1–6). Rituximab 250 mg/m2 followed by Zevalin 0.4 mCi/kg were given on day -14 and high-dose BEAM chemotherapy started on day -6. All pts engrafted in a median of 10 days after autoSCT (9–22). Zevalin had no impact on engraftment kinetics although 9 pts became neutropenic on or prior to the day of autoSCT, an uncommon occurrence with standard BEAM. There were no early infusion reactions associated with Zevalin. Two pts died of multi-organ toxicities early after SCT. One died from infection and one died of bronchiolitis obliterans (infection related) 4 and 5 months after SCT, respectively. The day100 rate of non-relapse mortality in these heavily pretreated pts with refractory lymphoma is 9% (95% CI, 2–33) and it seems there was no additional toxicity related to Zevalin. Overall, 21 pts are evaluable for response; 11 achieved CR, 9 achieved PR, 5 of whom converted to CR with additional radiation therapy to residual disease (overall 16 pts achieved CR), 1 pt did not respond. In all, seven pts relapsed or did not respond. The 1-year cumulative incidence of relapse is only 32% (95% CI, 17–60%). As expected in refractory disease, all relapses occurred within 6 months of autoSCT. With a median follow-up of 15 months (range, 4–25), 15 pts are alive. The estimated 1-year overall and progression-free survival were 59% (95% CI, 36–83%) and 49%, respectively, compared with less than 20% expected with standard autoSCT in this setting. In conclusion, inclusion of Zevalin in the conditioning regimen prior to autoSCT is relatively safe and may improve outcome in pts with refractory lymphoma. Although excess non-relapse mortality can not be ruled out, relapse rate was relatively low, resulting in improved PFS. Zevalin in combination with autoSCT merits further study in larger scale randomized studies. Moreover, standard risk pts with chemosensitive disease may also benefit from Zevalin followed by autoSCT combination.

Description: Reduced-intensity conditioning (RIC) regimens are increasingly used in allogeneic SCT. They are more effective when the underlying malignancy is in remission at the time of SCT. Various RIC regimens have been designed, yet there is no defined data as to whether any of the regimens has an advantage over the others. To answer this question we retrospectively analyzed SCT outcomes in 100 consecutive patients (pts) given RIC for various hematological malignancies including AML/MDS (n=45), ALL (n=8), CML (n=6), multiple myeloma (MM, n=18), various lymphomas (n=19), others (n=4). All pts were considered not eligible for myeloablative conditioning and were required to have chemo-sensitive disease at SCT. The median age was 56 years (23–75). Donors were HLA-matched siblings (n=53) or matched unrelated (n=47). RIC consisted of fludarabine with intravenous busulfan (6.4 mg/kg; FB, n=62) or with melphalan (100–140 mg/m2; FM, n=38). The FB group included older pts; median age 59(23–75) compared with 51(27–66) years in the FM group (p

Description: Relapse of AML/MDS after allogeneic SCT is associated with poor outcome. A subset of patients (pts) can be salvaged with donor lymphocyte infusion (DLI) with or without preceding chemotherapy or with a second SCT. It was previously speculated that pts given RIC may have a better chance to be salvaged than pts failing high-dose conditioning. To answer this question we retrospectively analyzed results of 171 SCTs for AML/ MDS with intravenous busulfan (ivBu) -based regimens. 58 pts were eligible for myeloablative conditioning and were given ivBu (12.8 mg/kg) and cyclophosphamide (BuCy). Among all others, 57 were given RIC consisting of fludarabine (F) and ivBu (FB2, 6.4 mg/kg) and 56 were given a modified myeloablative conditioning consisting of F and full-dose ivBu (FB4, 12.8 mg/kg). Median age was 40 (17–64), 60 (43–75) and 52 (18–66) years, respectively (p 6 months and 〈 6 months after SCT had a median survival of 7.2 and 1.4 months, respectively and estimated 2-year overall survival (OS) 22% (95C.I. 2–41) and 2% (95C.I. 0–7), respectively (p〈 0.001). The 2-year OS after relapse was 20%, 0% and 4% after BuCy, FB2 and FB4, respectively (p=0.04). SCT in refractory disease was also predictive of poor outcome after relapse in univariant analysis (p

Description: Background: Immunosuppressive therapy is a known risk factor for hepatits B reactivation. The highest risk is reported in hematologic patients treated with anti-CD20 monoclonal antibodies, glucocorticoids and hematopoietic stem cell transplantation. Currently, treatment with tyrosine kinase inhibitors (TKIs) in the vast majority of chronic myeloid leukemia (CML) patients is life-long. Recently healthcare professionals were advised to test for hepatitis B infection before initializing therapy with TKIs and closely monitor HBV carriers. The risk is considered class effect with all TKIs and recommendations are based on case reports. Aim: The aim of the current study was to evaluate the risk of hepatitis B reactivation in patients with CML treated with TKIs. Methods: The records of patients with CML treated with TKIs from a single center were systematically reviewed for hepatitis B serology and serum biochemistry. Results: One hundred eighty one patients diagnosed with CML between the years 1983 and 2016 were evaluated. The median age at diagnosis was 49.7 years (range 18-89), 117/181 (65%) males, with median duration of follow up with TKI therapy of 5.3 years (range 0.4 to 33 years). Over a total of 1195 years of therapy with TKIs no cases of HBV reactivation were identified. Among 114 patients with hepatitis serology, 11 patients (10%) had evidence of prior resolved HBV infection (HBsAg negative/anti-HBc positive). Two of them had anti-HBs positive serology, one had negative PCR for HBV DNA and other two patients received lamivudine prophylaxis. Only one patient had HBsAg positive serology. None of the patients with positive hepatitis serology had clinical or biochemistry evidence of hepatitis B reactivation. The 67 patients without available hepatitis serology had normal liver transaminases at 6 months of TKI therapy and at last day of follow up, confirming that no overt hepatitis B reactivation occurred. Conclusions: We evaluated hepatitis B reactivation in a rather large cohort of CML patients, treated with TKIs. Although there were no cases of HBV reactivation during long term follow up, it should be emphasized that even a low incidence may exert a significant risk due to the long duration of treatment in a chronic disease with lifelong therapy. Our study infers that patients with serology of prior resolved HBV infection are at low risk for hepatitis B reactivation. Larger cohorts of patients with positive hepatitis B serology in a multicenter long term evaluation should be performed in order to address current recommendations for patients' safety and concerns. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 2011 AlloSCT is the treatment of choice in advanced CML (〉CP1) and in Ph+ ALL. However, the post transplant relapse rate is high and outcome is rather poor in this setting. Nilotinib (Tasigna, Novartis Pharmaceuticals) is a very effective, second generation, novel TKI. Reduction of tumor mass pre- and maintenance therapy post alloSCT, may improve response rate and reduce transplant related toxicities (TRT) and relapses. The aim of the current study (CAMN107AIL03T) was to investigate whether nilotinib administration pre-alloSCT (400mg BID) and at escalating doses of 200–400mg BID post-alloSCT will intensify remission, reduce relapse and improve outcome without increasing TRT in pts with advanced CML and Ph+ ALL. 24 pts (M-13, F-11) participated in the study. The median age was 36 years (range, 18–58). 17 pts were with advanced CML (BC-10, AP-7) and 7 with Ph+ ALL. Cytogenetic and molecular responses were assessed by FISH and RQ-PCR (Taqman, LeukemiaNet and Eutos criteria). 5 pts harbored ABL kinas domain mutations by Sequenom assay (Y253H-2, A397P-1, E255K-1, M351T-1). 9 pts received nilotinib (400mg BID) pre-alloSCT and 6 responded (2 are too early to evaluate) (BC- CHR–2, BC - CCR-2, AP - PCR-1, AP - CHR-1). 22/24 pts underwent alloSCT (2 are pending) from an HLA-matched sibling (n=11), matched unrelated (n=8) or alternative donor (CB-2, Haplo-1). All, but one, had myeloablative conditioning (Bu/Cy or Flu/Bu-14, TBI/Cy-7). Graft versus host disease (GVHD) prophylaxis included CSA and methotrexate or MMF. 21/22 pts engrafted in median day+13 (range, 9–38) with 100% donor chimerism. TRT included mucositis in all pts, encephalitis-2, pericarditis-1, VOD-1 and infection-3. 3 pts died very early post transplant from sepsis and multi organ failure. Acute GVHD ≥ Gr II was observed in 10 pts (III-IV in 5). Chronic GVHD was observed in 15 pts (extensive – 9). Sixteen of the 22 transplanted pts received nilotinib (200mg × 2/d – 10, 300mg × 2/d – 6) starting at median day +38 (range, 30–158) post alloSCT. 6 pts did not receive nilotinib post alloSCT due to early death -3, progressive disease -1, severe pancytopenia -1, refusal -1. No pt received the planned 400mg BID dose. In 9 pts nilotinib administration was delayed due to either liver abnormalities -3, severe thrombocytopenia -3 or infection -3. Nilotinib dose had to be reduced (n=4) or stopped (n=3) due to Gr III-IV non-hematological toxicities -5 pts, mainly abnormal liver function tests -4 in combination with pruritus -1, vomiting -1 and abdominal pain -1, or hematological toxicities -2 pts. In 1 pt we observed increased levels of amylase without clinical signs of pancreatitis. QTc (470 msec) prolongation was observed in 1 pt. All, but 2 pts achieved MMR post alloSCT and 6 of them (CML) converted to CMR following nilotinib therapy. Response was durable and maintained. Only in 1 pt with disease progression kinas mutation (G205E and F359V) were detected. With a median follow up of 14.5 months (range, 0.5–36) 12 pts are alive while 12 died (Infection -5, GVHD -3, TTP-1, disease progression -3). In 2 pts disease progressed but responded to further therapy. 5 of 6 pts that did not receive nilotinib died (early death post AllSCT -3, disease progression -1, GVHD Gr IV -1). Immunological evaluation pre- and post nilotinib administration disclosed no significant change in T, B and NK cell numbers and T cell mitogenic response to PHA and anti CD3. Thymic output (TREC) and receptor repertoire (Spectrotyping) analysis indicates continuous thymopoiesis in 8/13 evaluated pts. NK cytotoxic activity against K562 increased in 9/15 evaluated pts. In conclusion, post alloSCT nilotinib maintenance therapy in extremely high risk pts with advanced CML and Ph+ ALL may prevent relapse and disease progression as 1) pts achieved MMR and 6 converted to CMR with nilotinib therapy and 2) only 5/16 pts that received nilotinib post alloSCT progressed [in 4 of them nilotinib could not be administrated as per protocol because of side effects (n=2) or low compliance (n=2)]. Although a formal maximal tolerated dose (MTD) of nilotinib post alloSCT has not been reached, it seems that administration of nilotinib early post alloSCT may be associated with increased toxicity. nilotinib administration post alloSCT does not impair immunological reconstitution, while GVHD incidence seems not to be reduced. Based on these data we would recommend nilotinib maintenance therapy post alloSCT in pts with advanced CML and Ph+ ALL. Disclosures: Nagler: Novartis: Honoraria, Research Funding. Off Label Use: Nilotinib (Tasigna) for reduction of tumor mass pre- and maintenance therapy post alloSCT in patients with CML and Ph+ ALL (novel TKI).