ALBERT

Description: Key Points Mixed, atypical, and warm immunoglobulin G plus C AIHA (∼30% of cases) more frequently have a severe onset (Hb ≤6 g/dL) and require multiple therapy lines. Infections, particularly after splenectomy, acute renal failure, Evans syndrome, and multitreatment, were predictors of fatal outcome.

Description: Introduction. Discontinuation (D/C) of Imatinib or other TKIs in Chronic Myeloid Leukemia (CML) represents an important issue in the management of this disease. It is generally accepted that relapse develops (and treatment must be resumed) when patients (pts) lose Major Molecular Remission (MMR), i.e. when the amount of the BCR-ABL1 transcript, measured in peripheral blood by RT-PCR, exceeds 0.1 %. The Imatinib Suspension And Validation (ISAV) study, which started in 2011, enrolled pts with CML treated with Imatinib who showed no evidence of BCR-ABL1 transcript for at least 18 months before enrollment. Methods. A digital PCR (dPCR) for BCR-ABL1 was performed at the time of Imatinib D/C while a second dPCR was performed when non relapsed patients exited the study, 36 months later. dPCR experiments were performed by the QX200 system (BioRad) in the same lab and using the same methodology. The BCR-ABL1 fusion and ABL1 transcripts were quantified using DigiDrop P210 MasterMix and DigiDrop P210 Positive Control (Bioclarma), according to manufacturer's protocol. The target concentration in each sample was expressed as percentage of BCR-ABL1/ABL1. Results. A total of 107 pts were enrolled in the ISAV study. Relapses occurred in 54 pts (52%); among the 53 non relapsed pts, 41 (77%) presented at least one positive RT-PCR result following Imatinib D/C, and only 12 (23%) maintained PCR negativity throughout the duration of the study. Among the non-relapsed pts dPCR performed at treatment D/C showed positivity in 20.6% of cases (95% confidence interval [C.I.] 9-36%), while 91.1% of pts (95%, C.I. 80-97%) evaluated 36 months later showed a positive dPCR value, although no patient resumed treatment. The evaluation of non relapsed pts by dPCR showed that mean values at D/C were 0.00143% +/- 0.0006 (SE); when tested at study exit, the same pts showed average dPCR values of 0.0115 % +/- 0.002. This difference is statistically highly significant and corresponds to a change of approximately 1 log in the residual tumor burden: from 2x107 to 2x108 cells. There was no correlation between the results of RT-PCR performed during the study and the dPCR status at study exit: pts who tested negative by RT-PCR during the study were uniformly negative in dPCR at D/C but tested positive at study exit in 83.3% of cases; pts who showed at least on positive RT-PCR during the study showed positivity by dPCR in 25% at D/C and in 89.3% at study exit. Finally, half of the pts who tested negative by dPCR at study exit showed dPCR positivity when tested at the time of Imatinib D/C. Conclusions. These results show that during a three year period, the D/C of Imatinib led to the increase of approximately 1 log in the tumour burden of non-relapsed pts, although none of them lost MMR and resumed treatment. These data strongly indicate the need for a long-term monitoring of pts who D/C Imatinib; they also suggest that the functional status of residual CML cells rather than their number could represent the critical factor to predict the tumour load present after 3 years of Imatinib D/C. Disclosures Le Coutre: Incyte: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Speakers Bureau. Elena:Novartis: Consultancy; Pfizer: Consultancy. Assouline:Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria. Stagno:Incyte: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; BMS: Honoraria. Iurlo:Novartis: Other: Speaker Honoraria; Incyte: Other: Speaker Honoraria; Pfizer: Other: Speaker Honoraria. Kim:Novartis: Research Funding; BMS: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; Il-Yang co.: Research Funding. Fava:Pfizer: Honoraria; Novartis: Honoraria; Incyte: Honoraria; BMS: Honoraria. Gambacorti-Passerini:Bristol-Meyers Squibb: Consultancy; Pfizer: Honoraria, Research Funding.

Description: T/NK “nasal type” lymphoma is a neoplasm that shows a peculiar geographical distribution. In fact most of the reported cases come from Far Eastern countries such as Hong Kong, and Central America, particularly from Mexico; this kind of lymphoma occurrs rarely in western countries. Between 1997 and 2004, 19 new cases of T/NK nasal type lymphoma were diagnosed in 7 Italian Hematology Division. Patients characteristics were as follows: all caucasian; 14 men and 5 women; median age 53 years (range 20–80). The presentation at the onset was in the nasal cavity or adjacent structures in 15 cases, who presented symptoms like nasal obstruction, dysphagia, orbital edema; in 2 cases, skin lesions were the first sign of disease, followed by oropharingeal involvement; in 1 case, the patient was studied because of migrating bone pain, and in the last patient lymphoma presented as a right leg tumor. Considering the stage of disease, 10 patients presented a I stage (in 8 cases IA, 1 IB, and 1 IE); 3 patients were in stage II (2 IIB, 1 IIE); 6 patients presented an advanced stage disease (3 IVA, 3 IVB). Thus, early stage patients were 13, while advanced stages were 6. The median time from the onset of signs, as skin lesions, or symptoms, as nasal obstruction to diagnosis was 3 months, ranging between 1 and 24. Diagnosis was based on the finding of a T/NK phenotype by the histological examination of oropharingeal or cutaneous lesions in 17 cases, bioptical examination of the leg tumor in another patient, and by a bone marrow biopsy in the patient who presented bone pain. All patients were treated with chemotherapy alone (8 cases), or associated to radiotherapy (10 cases); 1 patient underwent chemotherapy, radiotherapy, and surgery. Chemotherapy regimens usually adopted contained anthracyclines (11 cases); in the other cases patients were treated with CVP (2 cases), low dosages of cyclophosphamide (1), cyclophosphamide-vinblastine-mithoxantrone-bleomicine (1), DHAP (3). Radiation dosages ranged between 27.5 and 47.5 Gy, with a median dosage of 40 Gy. Eight patients reached a clinical improvement, while 11 patients resulted refractory or presented a limited response to therapy The overall median survival time was 5 months (range from 1 to 48): Eleven patients died within 14 months from diagnosis, and the median survival time of this group was 6 months. At last follow-up (June 2004) 8 patients are still alive, with a time from diagnosis ranging beteween 2 and 48 months. The preliminary results of this retrospective survey confirmed that T/NK nasal type lymphoma is a very rare lymphoma in italian population, and it is characterized by a very bad prognosis. The rarity of this disease cause a lacking of a standardized therapeutic approaches. More data are needed to know the epidemiology of this kind of lymphoma in Europe.

Description: Abstract 3206 Background: Conventional therapy of warm autoimmune hemolytic anemia (WAIHA) include administration of corticosteroids and immunosuppressive agents, or splenectomy, whereas no effective treatment exists for cold hemagglutinin disease (CHD). A substantial proportion of patients with WAIHA do not respond to or relapse after corticosteroid therapy and may experience clinically relevant side effects. Favorable responses to rituximab at standard doses (375 mg/m2 weekly for 4–6 courses) have been reported in both WAIHA and CHD, idiopathic or secondary, as well as in other autoimmune diseases, such as rheumatoid arthritis and primary immune thrombocytopenia. Recently, low dose (LD)-rituximab (100 mg fixed dose weekly for 4 courses) has been proven effective in patients with autoimmune cytopenias, particularly immune thrombocytopenia. Aims: To evaluate the safety, activity and the duration of the response of LD-rituximab associated with standard oral prednisone (PDN) as first line therapy in newly diagnosed WAIHA and CHD, and as second line therapy in WAIHA relapsed after standard oral PDN. To correlate the clinical response to biological parameters (cytokine and anti-erythrocyte antibody production). Methods: In this single-arm prospective pilot study, LD-rituximab was administered at 100 mg fixed dose weekly on days +7, +14, +21, +28 along with standard oral PDN (1 mg/kg/die p.o. from day +1 to + 30, followed by quick tapering: 10 mg/week until 0.5/mg/kg/die, then 5 mg/week until stop). Complete and partial initial responses (iCR and iPR) were defined as Hb 〉/= 12 g/dL and 〉/= 10 g/dL at month +2 from the beginning of therapy, respectively; sustained response (SR) was defined as Hb 〉/= 10 g/dL at month +6 and +12, in the absence of any treatment. Mitogen stimulated cultures were performed to measure anti-RBC antibodies (at enrolment and month +1, +3, +6 and +12) and cytokines (at enrolment and month, +3, and +6) by ELISA. Results: Twenty-one patients (14 female, 7 male; median age 52 yrs, range 28–77) were enrolled after informed consent. The median follow-up was 11 months (range 2–25). An iCR and iPR were observed in 14 (67%) and 4 (19%) out of 21 patients, respectively; the median Hb level increased from 9.1 g/dL (range 4.4–12.3) at enrolment to 12.5 g/dL (range 9.1–15.3) at month +2. A SR at month +6 was observed in 13/14, and at month +12 in 11/11 evaluable patients. A total of 3 patients relapsed: one at month +16 (retreated with the same protocol with iPR at month +18), another at month +7 (retreated with a SR at month +13), ad the last at month +5 (splenectomy planned). No side effects or serious adverse events were observed. For 10 relapsed AIHA patients (with a follow-up post treatment of at least 12 months) laboratory data (Hb, LDH, reticulocytes) and steroid administration were available before LD-rituximab treatment: a lower cumulative dose (roughly 50%) of steroid was administered to patients during LD-rituximab study compared with previous therapy, without significant differences in the general trend of Hb, LDH, and reticulocytes. Biological studies showed that anti-RBC antibody production decreased until month +6 (from 556 ng/ml at enrolment to 125 ng/ml) and slightly increased at month +12 (307 ng/ml). Regarding cytokine production, at enrolment TNF-α, IFN-γ, IL-12 and TGF-β were lower in patients vs controls, and increased at month +6, without reaching normal values. IL-17 was 10-fold normal values at enrolment, and diminished during the follow-up without reaching normal values. These preliminary results seem to indicate that the addition of LD-rituximab to standard corticosteroid therapy is a feasible and active treatment in AIHA. Data on SR are intriguing, particularly regarding the possible steroid sparing effect of LD-rituximab. Cytokine and anti-erythrocyte antibody production offer new insights into the immunomodulating activity of the drug. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction. The application of Pediatric-Type Therapy (PTT) programs to adults with ALL can improve outcome significantly despite higher age-related toxicity. Recent series reported survival rates ≥ 50%, but only few combined PTT with Minimal Residual Disease (MRD) study for risk-oriented Hematopoietic Cell Transplantation (HCT) and/or explored the value of specific PTT element such as higher dose, lineage-targeted MTX up to 5 g/m2. Methods. To improve over prior data, NILG protocol 10/07 (Clinical.Trials.gov NCT-00795756) for unselected adult patients aged 18-65 years combined PTT together with MRD study for risk/MRD-based HCT. The 8-course program consisted of a 5-drug complete remission (CR) induction (cycle no. 1; imatinib added if Ph+) followed by 3 modified BFM blocks (no. 2, 4 and 6), 3 lineage-targeted MTX blocks (no. 3, 5 and 7; MTX 5 g/m2 for T-ALL and 2.5 g/m2 for B-ALL [1.5 g/m2 if age 〉 55 years or Ph+]; no. 3 and 7 with high-dose Ara-C 2 g/m2 x4, no. 5 with L-Asp 10,000 IU/m2 x2) and reinduction (no. 8). CNS prophylaxis was with triple intrathecals or liposomal cytarabine (Haematologica 2015;100:786). MRD was studied molecularly with sensitive probe(s) (sensitivity 10-4 or greater) on marrow samples obtained at end of induction (week 4, w4) and after cycles 3 (w10), 5 (w16), 7 (w22) i.e. after 1st, 2nd and 3rd lineage-targeted MTX block. Patients were risk-stratified at diagnosis and after MRD analysis for the purpose of allocation to HCT or conventional maintenance. The HCT allocation cohort consisted of predefined very high-risk patients (vHR: WBC 〉100, highly adverse cytogenetics, pre-T/mature T-ALL) regardless of MRD, of HR patients without MRD study (HR: late CR; B-ALL with WBC 〉30 or pro-B phenotype), and of HR or standard-risk (SR) patients with MRD ≥ 10-4 at w10/16 or positive at w22. Conversely, the maintenance allocation cohort consisted of SR and HR patients with MRD 〈 10-4 at w10/16 and negative at w22 and of SR patients without MRD study. A family related/unrelated donor search was activated at diagnosis in order to proceed to HCT soon after cycle no. 3 when needed. Results. 205 patients were enrolled, with a median age of 41 years (range 17-67 years, 11% 〉 60 years). 55% were male, 42 had Ph+ ALL, 119 Ph- B-ALL and 44 T-ALL. Of 163 patients with Ph- ALL, 45% were SR, 13% HR and 42% vHR. CR rate was 98% in Ph+ ALL and T-ALL, and 83% in Ph- B-ALL (88% vs 58% in patients ≤ vs 〉 60 years, P .0013). The MRD study was successful in 109/142 CR patients with Ph- ALL (77%), contributing to the final risk classification in 63 patients, of whom 41 were MRD responsive (65%) and 22 MRD resistant (35%). Altogether, 55 CR patients constituted the maintenance allocation group (39%) and 87 the HCT allocation group (61%), which included mainly vHR patients (n=61, 43%) selected for HCT independently of MRD study results. According to intention-to-treat, median OS is not reached (53% at 5 years, figure) and median DFS is 4.8 years (48% at 5 years). In Ph- ALL, 5-year OS/DFS are 74%/61% in T-ALL (medians not reached) and 48% each in B-ALL (medians 3.9 and 4.7 years). Median OS is not reached in both HCT and maintenance allocation groups (58% and 73% at 5 years, respectively, P .078), with a median DFS of 4.7 years (48% at 5 years) versus not reached (59% at 5 years) (P .19). Treatment adherence was good with some exceptions in maintenance allocation group (6 HCT, 11%) and a transplant realization of 68% (53 allogeneic; 6 autologous) in HCT allocation group. With HCT, 5-year incidence of nonrelapse mortality was 17%. The MRD analysis proved that DFS of patients achieving an MRD response 60 years. 5-year OS and DFS of 55% and 52% respectively in Ph- patients aged up to 65 years represent an improvement over prior NILG study (5-year OS and DFS of 36% and 35% respectively). MRD was essential in orientating the HCT choice in SR and HR patients and retained a major prognostic role in all patients. Optimizing the early MRD response with new immunotherapeutics and clarifying the role of HCT in MRD responsive vHR patients are some relevant topics of future research. Figure Figure. Disclosures Ciceri: MolMed SpA: Consultancy. Vitolo:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Gilead: Honoraria; Celgene: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Gallamini:Millenium Takeda: Membership on an entity's Board of Directors or advisory committees.

Description: Abstract 2050 Poster Board II-27 BACKGROUND: Most patients with APL have a favorable outcome after treatment with all-trans-retinoic acid (ATRA), and most of those who fail can be successfully treated with arsenic trioxide (ATO). However, a few patients may not respond or eventually relapse after therapy with these agents. Tamibarotene is a synthetic retinoid that has been reported to be well-tolerated and effective in APL in studies in Japan. Treatment with tamibarotene is associated with a low incidence of differentiation syndrome and it has no effect on QTc interval. METHODS: Patients with APL refractory or relapsed after treatment with both ATRA and ATO (sequential or concomitant) were eligible, with no limit on the total number of prior therapies. Pts received tamibarotene orally at a daily dose of 6 mg/m2 divided in two doses until remission or a maximum of 56 days. After remission, patients could continue consolidation courses with the same dose for 4 weeks every 8 weeks for a maximum of 3 courses. RESULTS: Nine patients have been treated, 4 female, median age 57 years (range, 45-60). Patients had received a median of 7 prior therapies, and 1 had received two prior stem cell transplants (SCT). At the start of therapy the median WBC was 2.6 ×109/L (0.29 to 16.7) and platelet count 50 ×109/L (22 to 121). Of the 9 pts treated, 3 (33%) achieved a hematologic CR and 4 (44%) a morphologic leukemia-free state. After induction, 3 (33%) patients had achieved a cytogenetic remission and 1 (11%) had undetectable PML-RARα transcript levels. One patient went to SCT after achieving CR and died in CR of GVHD. The two other CRs continued with consolidation therapy and received 2 and 3 cycles, respectively. One of them relapsed after completing all treatment. Remissions have been sustained for 3+ and 8 months, respectively. Treatment was well tolerated. Differentiation (“ATRA”) syndrome was observed in 1 patient that resolved with medical management without requirements for treatment interruption. Other toxicities possibly related to tamibarotene include dry mouth in 2 (22%) patients, neutropenia in 1 (11%), generalized weakness in 1 (11%), joint pains in 1 (11%), hypertriglycerdemia in 1 (11%), vomiting in 1 (11%), diarrhea in 1 (11%), leg edema in 1 (11%), and bone pain in 1 (11%) patient. Grade 3-4 adverse events possibly related included neutropenic fever in 1 patient (11%), syncope in 1 patient (11%), and somnolence in 1 patient (11%). CONCLUSION: These results suggest that tamibarotene is an effective agent for management of APL. Based on the favorable results observed in this heavily pre-treated population, studies of tamibarotene in combination with other agents as initial therapy are being planned. Disclosures: Wieland: CytRx Corporation: Employment, Equity Ownership. Barber:CytRx Corporation: Employment, Equity Ownership.

Description: Abstract 2029 Poster Board II-6 In a prospective NILG (Northern Italy Leukemia Group) study, short IM pulses were added to chemotherapy in order to 1) reduce incidence of early failures, 2) obtain higher transfer rates to stem cell transplantation (SCT), and 3) improve survival in comparison with a prior patient cohort treated with the same chemotherapy program without IM. IM 600 mg/d was given orally for 7 consecutive dd. with each chemotherapy block, starting from day 15 of induction (IDR/VCR/PDN±ASP) and day –3 of the following consolidation courses (5x IDR/VCR/CY/DEXA; 2x HD-MTX/ARA-C). All pts. received CNS chemoradioprophylaxis and were eligible to allogeneic SCT, or alternatively to HD therapy with autologous SCT and long-term maintenance with 6MP/MTX and intermittent IM. Between April '00 and November '08, 100 out of 404 pts. registered in NILG study 09/00 had Ph+ ALL (Ph chromosome and/or BCR-ABL rearrangement). M/F ratio was 1.17 and median age 46 years (range 19-66). 35 pts. constituted the control cohort (IM-) while, starting December '02, 59 pts. were included in the modified protocol (IM+), and 6 were excluded from analysis because treated on a continuous IM schedule. Of 59 IM+ pts., 53 received IM during induction/consolidation as planned and 6 during consolidation only (included in IM- group for remission induction analysis). Outcome to induction therapy of IM+ vs. IM- group was: CR 49/53 (92%) vs. 33/41 (80%), NR 2 (3.7%) vs. 5 (12%), ED 2 (3.7%) vs. 3 (7%) (P=NS). With a median observation interval from diagnosis of 5 years (range 0.6-9.2 years), 21 IM+ vs. 6 IM- pts. are alive in remission (CR1 pts.: 43% vs. 18%, P=0.02), and both OS (Figure) and DFS (0.39 vs. 0.21, P=0.044) rates at 5 years are significantly improved in IM+ group, especially when IM was administered from the induction cycle. The ability to perform a SCT increased from 53%(n=15: 11 allogeneic, 4 autologous) to 68%(n=37: 22 allogeneic, 5 autologous), partly owing to lower incidence of early relapse (26% vs. 56% at 1 year, P=0.005). SCT-related mortality was not different (P=0.58) and postgraft survival probability at 5 years was 0.45 overall, again with no difference related to SCT source or IM. Use of IM was not associated with greater reduction of BCR-ABL transcripts: by PCR analysis of BM samples taken at weeks 10, 16 and 22 in pretransplantation pts., a major response (absent/

Description: Autoimmune hemolytic anemia (AIHA) is a greatly heterogeneous condition both in terms of clinical presentation and response to treatment, usually classified as warm (WAIHA), cold (CAD), mixed, and atypical forms. The aim of this study was to identify predictors of outcome and response to therapy considering in particular the serological characteristics and the severity of anemia at onset. We evaluatedretrospectively 307 patients (112 M and 195 F, median age at diagnosis 63, range 1-97), diagnosed between 1978 and 2013 and followed-up for a median of 33 months (range 12-372); 60% of cases were WAIHA, 27% CAD, 8% mixed, and 5% atypical (14 DAT- and 1 DAT+ for IgA only). Hemoglobin values were lower in mixed (median 5.8, range 2-10.7 g/dL) atypical (6.2, 3-9), and in IgG+C3 DAT+ WAIHA (6.9, 2.9-11.5). Twenty-one subjects were diagnosed with Evans’ syndrome, the majority of them WAIHA, with a severe onset. Considering anemia at onset, 27% of cases had Hb levels 10 g/dL; the most severe cases were mainly mixed and atypical forms (P=0.0001). Regarding therapy, 47% of cases were treated with one therapy line only, 26% with two, 13% with three, and 4% with four or more lines. Sixty % of WAIHA received first line steroid therapy only, 20 CAD required no treatment, and patients with IgG+C DAT+ WAIHA, mixed, and atypical forms were more frequently treated with 2 or more therapy lines (P

Description: In paroxysmal nocturnal hemoglobinuria (PNH) hemolytic anemia is due mainly to deficiency of the complement regulator CD59 on the surface of red blood cells (RBCs). Eculizumab, an antibody that targets complement fraction 5 (C5), has proven highly effective in abolishing complement-mediated intravascular hemolysis in PNH; however, the hematologic benefit varies considerably among patients. In the aim to understand the basis for this variable response, we have investigated by flow cytometry the binding of complement fraction 3 (C3) on RBCs from PNH patients before and during eculizumab treatment. There was no evidence of C3 on RBCs of untreated PNH patients; by contrast, in all patients on eculizumab (n = 41) a substantial fraction of RBCs had C3 bound on their surface, and this was entirely restricted to RBCs with the PNH phenotype (CD59−). The proportion of C3+ RBCs correlated significantly with the reticulocyte count and with the hematologic response to eculizumab. In 3 patients in whom 51Cr labeling of RBCs was carried out while on eculizumab, we have demonstrated reduced RBC half-life in vivo, with excess 51Cr uptake in spleen and in liver. Binding of C3 by PNH RBCs may constitute an additional disease mechanism in PNH, strongly enhanced by eculizumab treatment and producing a variable degree of extravascular hemolysis.

Description: Introduction. It is known that imatinib can be safely discontinued in patients (pts) with Chronic Myeloid Leukemia (CML) with minimal residual disease. Here we report an update of the Imatinib Suspension And Validation (ISAV) study at 79 months (mts) from study initiation to provide long term follow up data. Aims. The ISAV study aims to validate the capability of digital PCR (dPCR) to predict relapses after imatinib discontinuation in CML pts with negative Q-RT-PCR and to evaluate relapse rate, time to recurrence, survival and the impact of imatinib treatment on Quality of Life (QoL). Methods. This study involves 15 sites, 10 in Italy and 1 in each of the following countries: Germany, Spain, The Netherlands, Canada and Israel. CML pts (chronic or accelerated phase) treated with imatinib for more than 2 years and in complete molecular remission (CMR) were eligible. Patients had to be in CMR for at least 18 mts, with a minimum of 3 Q-RT-PCR performed at their own sites. After discontinuation of imatinib therapy, Q-RT-PCR was performed monthly (mts 1-6), bimonthly for 36 mts and then every 6 mts for additional 2 years, to assess the maintenance of the molecular remission. The loss of molecular remission was defined as two consecutive positive Q-RT-PCR tests with at least one BCR-ABL/ABL value above 0.1%. Patients losing molecular remission resumed imatinib treatment at the same dosage used before interruption. dPCR was performed at screening and at 36 mts for those pts who were still in remission. Patients' QoL during imatinib discontinuation/resumption was evaluated through the EORTC QLQ-C30 questionnaire. Results. The ISAV study enrolled 112 pts with a median follow-up time of 60.0 mts [95% CI: 59.6-60.6] for pts who do not relapsed; 66.1% of them completed the study as per protocol. The 58.9% of pts were male and 37.4% were aged 65 or older; median duration of imatinib treatment was 103.2 mts with median duration of CMR of 25.6 mts before imatinib discontinuation. At 79 mts from imatinib discontinuation, 56 pts of the 107 eligible ones relapsed and resumed imatinib with a relapse rate of 52.3% [95%CI: 20.4-32.6]; 69.6% of them relapsed in the first 9 mts. Of the 52 not-relapsed pts, 40 (76.9%) regained Q-RT-PCR positivity without losing MMR. In this latter group 2 pts experienced late relapses, at 30.6 and 45.5 mts respectively. A loss of CCyR occurred in 13 pts (23.6%): 10/13 CCyR losses were recovered, the remaining 3 were not assessed for response. No case of CML progression or resistance to imatinib was observed. After the resumption of imatinib the median time to MMR/CMR was 1.8 [95% CI: 1.0-2.0] mts. No significant correlation between relapse and previous duration of imatinib treatment, use of interferon, time to CCyR, Sokal score or duration of CMR was identified, while an inverse relationship between pts age and risk of relapse was evident. dPCR results before imatinib discontinuation showed that 23.4% of pts were positive and 76.6% negative at the time of discontinuation, with a Negative Predictive Value ratio (dPCR/Q-RT-PCR) of 1.1 [95%CI: 0.99-1.22]. At 36 mts from imatinib discontinuation 80.4% [95%CI: 30.6-50.4] of the pts tested were positive in dPCR. Moreover, the results of dPCR performed at imatinib discontinuation and age together can predict the risk of relapse: pts with less than 45 years and with a positive dPCR had the highest risk of relapse (100%) as opposed to pts ≥45 years and with negative dPCR (36.1%). The analysis of QoL evidenced a statistically significant improvement in the general well-being and symptoms scales at 1 month after imatinib discontinuation, particularly with regard to nausea, diarrhea, fatigue and insomnia (p