ALBERT

Description: Abstract 2934 Background: Since MDS is more prevalent in the elderly, use of intensive chemotherapy is considered to be difficult. However, granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF), use of clean room and development of promising antifungal agents have resulted in dramatically enhanced safety of post-chemotherapy control of elderly patients. Thus, we attempted to use intensive chemotherapy in HR-MDS and MDS-AML patients. Objectives: To evaluate, in HR-MDS and MDS-AML patients, the efficacy and safety of remission induction therapy and post-remission therapy that are standard treatment for de-novo AML in our department.This study enrolled 213 consecutive patients initially treated at our department between 2000 and 2010 who suffered MDS-related disease and whose survival was expected to be less than several months with supportive therapy alone. Almost all of the patients had ≥20% myeloblasts. The age of the patients ranged from 16 to 93 years (median: 70 years). They comprised 2 with good prognosis, 107 with intermediate prognosis and 104 with poor prognosis based on chromosomal findings. Methods: Remission induction therapy consisted of behenoyl-ara-C (BHAC) 350 mg/m2 (300 mg/m2 for patients aged ≥70 years) over 10 days and idarubicin (IDA) 12 mg/m2 (10 mg/m2 for patients aged ≥70 years) over 4 days. Additional etoposide 100 mg/m2 over 4 days was given if bone-marrow examination on Day 15 revealed residual myeloblasts of ≥5%. The efficacy of the therapy was evaluated after the first course. Patients showing maintained remission received 8 courses of post-remission therapy over 11 months. This post-remission therapy included high-dose cytarabine (2 g/m2, or 1g/m2 for patients aged ≥60 years) (HDAC) × 10 and mitoxantrone (MIT) 7mg/m2 × 3 given initially after remission. Maintenance/intensification therapy mainly consisted of BHAC 350 mg/m2 × 4 plus aclarubicin (ACR) 20 mg/body × 6 or IDA 10 mg × 1 alternately every 5 weeks. Outpatient maintenance therapy consisted of M-CSF over 7 days after the end of chemotherapy, followed by administration of G-CSF until neutrophil recovery. Patients were admitted to a clean room if WBC became

Description: Abstract 1052 Poster Board I-74 Background: Until recently, intensive chemotherapy for acute myeloid leukemia (AML) did not necessarily lead to high success rates, partly because of deaths from infections due to the associated long-term neutropenic phase. However, the advent of effective antifungal agents or the use of granulocyte colony-stimulating factor (G-CSF) or macrophage colony-stimulating factor (M-CSF) has definitely reduced deaths from chemotherapy and has improved the results of treatment with intensive chemotherapy also in elderly patients. Objectives: The complete remission rate after remission induction therapy and the event-free survival (EFS) after postremission therapy were investigated in 165 patients (99 men and 66 women) with untreated de novo AML (excluding subtype M3) who were consecutively registered in a single institution between March 2001 and March 2009. The patients' ages ranged from 16 to 94 years (median: 59 years). There were 3 patients with M0, 18 patients with M1, 25 patients with M2, 25 patients with t(8;21), 35 patients with M4, 12 patients with M4Eo, 35 patients with M5, 10 patients with M6, and 2 patients with M7. Methods: Remission induction therapy consisted of 10 days of behenoyl-ara-C (BHAC) at 350 mg/m2 (300 mg/m2 for patients 70 years or older) and 4 days of idarubicin (IDA) at 12 mg/m2 (10 mg/m2 for 70 years or older). Further, if bone marrow examination revealed 5% or more residual blast cells on day 15, etoposide was additionally administered at a dose of 100 mg/m2 for 4 days. The efficacy of the remission induction therapy was evaluated after 1 course of treatment. The patients who had achieved remission underwent 9 courses of postremission therapy, which lasted 11 months. The details are omitted, but therapy with high-dose (2 g/m2 [1 g/m2 for patients 60 years or older]) cytarabine (HDAC)×10 plus 7 mg/m2 of mitoxantrone (MIT) ×3 was performed during the 1st and 9th courses. No HDAC was performed on the elderly aged above 75 years old. The intensive therapy with Aclarubicin (ACR) of 20 mg/body for 14 days and the maintenance therapy with a combination of BHAC 350 mg/m2×4 with ACR or IDA were repeated alternately every 6 weeks. Chemotherapies other than remission induction therapy and HDAC were performed in an outpatient clinic, and if the patients with the WBC decreasing to 1000/mm3 were hospitalized in the biological clean room. M-CS was administered for 7 days after the day following the end of chemotherapy, and subsequently G-CSF was administered until the WBC becomes to be 1000/mm3. Results: Complete remission (CR) was achieved in 143 of the 165 patients overall (86.7%), 113 of the 123 patients 69 years or younger (92.7%), and 29 of the 42 patients 70 years or older (69.1%). During the remission induction therapy, death occurred in 6 of the 165 patients overall (3.6%), 2 of the 123 patients 69 years or younger (1.6%), and 4 of the 42 patients 70 years or older (9.5%). The EFS in patients with CR was 61.5% at 8 years in patients 69 years or younger, while it was 26.9% at 5 years in patients 70 years or older. There was only a case of death due to chemotherapy during postremission therapy. Seven patients underwent bone marrow transplantation during the first remission, and 6 of these patients have been enjoying EFS. Conclusion: Improvement in supportive care has enabled safe intensive chemotherapy. The patients with good or intermediate prognosis were clearly improved by the present preliminary treatment at a single institution, but the patients with poor prognosis still highly require bone marrow transplantation in the future. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 3295 WT1 (Wilms' tumor gene 1) encodes a transcription factor, which regulates various types of genes and plays an important role in cell proliferation and differentiation. WT1 is highly expressed in leukemia and various types of solid tumors. In vivo immunization of mice with MHC class I-restricted 9-mer WT1 peptide elicited WT1-specific cytotoxic T lymphocytes (CTLs) and rejected WT1-expressing leukemia cells, demonstrating that WT1 is a tumor rejection antigen. Next, identification of human HLA class I-restricted WT1 peptides was performed, and WT1 235 (235-243 aa) and WT1 126 (126-134 aa) were determined as an HLA-A*2402- or HLA-A*0201- restricted WT1 peptide, respectively, by using in vitro WT1-specific CTL induction assay. On the basis of these fundamental experiments, we performed for the first time a phase I clinical trial of WT1 peptide immunotherapy with the approval of our ethical committee. A total of 26 patients with acute myeloid leukemia (AML), myelodysplastic syndrome, breast or lung cancer were intradermally injected with a HLA-A*2402-restricted natural or modified 9-mer WT1 peptide emulsified with Montanide ISA51 adjuvant at 0.3, 1.0 or 3.0 mg at 2-week intervals. As shown in Table1, 12 AML patients were WT1-vaccinated and eight of the 12 AML patients were evaluable for clinical effect because of the existence of minimal residual disease (MRD) assessed by WT1 mRNA assay. Since four of the eight patients had obvious clinical response with the decrease in WT1 mRNA within three injections of WT1 vaccine, WT1 vaccination was repeated for them afterward (in the case that clinical response was not obvious within three injections of WT1 vaccine, WT1 vaccination was discontinued). However, one patient (No. 20) had re-increase in WT1 mRNA and WT1 vaccination was discontinued. The remaining three patients (Nos. 21, 23 and 24) have been repeatedly receiving WT1 vaccination (intervals were changed from 2 weeks to one month) over 7 years until now. WT1 mRNA levels, which directly reflected the amount of leukemic blast cells, were abnormally high and 102-103 copies/mg RNA in PB (normal level is 〈 50 copies/mg RNA) before WT1 vaccination in these three AML patients, showing that the patients were at molecular relapse with MRD. In nos. 21 and 23 patients, a decrease and increase in WT1 mRNA levels were repeated during early stages of WT1 vaccination. However, afterward, WT1 mRNA levels gradually decreased and reached normal level approximately three and a half years after the beginning of WT1 vaccination and have been maintained at normal level until now. In patient no. 24, high levels of WT1 mRNA (near 103 copies) gradually decreased by repeated WT1 vaccination and returned to normal level approximately 5 years after the beginning of WT1 vaccination although it was much delayed. Thus, these three patients had achieved continuous complete remission regardless of high risk for clinical relapse. WT1-specific immune responses were evaluated by WT1 tetramer assay. Frequencies of WT1-specific cytotoxic T lymphocytes (CTLs) (WT1 tetramer+ CD8+ T cells) in the patients were already higher before WT1 vaccination, compared to those in healthy volunteers, which was a frequent phenomenon in WT1-expressing tumor-bearing patients, but the WT1-specific CTLs were a IFN-g− inactivated form. After WT1 vaccination, a IFN- g+ activated from of WT1-specific CTLs appeared and was maintained until now. No adverse effects except local erythema and eruption at the injection sites of WT1 vaccine were observed regardless of repeated long-term WT1 vaccination over 7 years. These finding indicated that WT1-specific CTLs could attack WT1-expressing leukemic blast cells but ignored WT1-expressing normal cells such as podocytes of kidney and progenitor cells of various types of organs. In conclusion, we presented here the first report of promising clinical outcome of very long-term WT1 vaccination for AML patients with high risk for relapse. WT1 peptide immunotherapy should have good prospects as a cure-oriented therapy for AML and could be the first choice of the treatments for AML patients who had still MRD after induction chemotherapy, especially for elder patients who were intolerable to intensive chemotherapy. WT1 peptide immunotherapy may be also a better choice of treatments for AML patients who have high risk for relapse but are intolerable to allogeneic hematopoietic stem cell transplantation. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 3767 Background With the introduction of imatinib (IM) and subsequent TKIs such as nilotinib (NI) and dasatinib (DA), deaths due to progression of chronic myeloid leukemia (CML) have decreased dramatically. In such circumstances, the new occurrence of other malignant diseases in patients with CML on treatment with TKIs always causes distress. With the increase in long term surviving patients with CML, there is concern over whether these malignancies are related to treatment with TKIs or not. We investigated the improved prognosis in patients with CML on long-term treatment with TKIs and the occurrence of complicating malignancies. Methods We evaluated 173 patients (101 males, 72 females) in the chronic phase of CML, all of whom had CML diagnosed at our hospital between January 1990 and June 2011 and received treatment with TKIs for at least 1 year. The median age at the start of treatment with TKIs was 57 (19 – 92) years. Patients aged 60 years and older accounted for 72 (42%). The median follow-up period after the start of treatment with TKIs was 68 (12 – 128) months. Before the onset of CML, 11 patients had prior malignancies. Treatments for CML administered before use of TKIs were hydroxyurea (HU) alone 3, HU + interferon-α (IFN-α) 47, IFN-α alone 7, chemotherapy for AML + IFN-α 2 and chemotherapy for ML + IFN-α 1. TKIs were used as frontline therapy in 113.TKI treatment of all patients initially consisted of IM at the dose of 100 mg per 12 kg body weight. We switched the drug to NI when complete molecular response (CMR) was not achieved after long-term treatment with IM. In addition, a switch to DA was used to consolidate CMR. Treatments that contained TKIs consisted of IM alone in 42, IM → NI in 46, and IM →NI → DA in 85. Two patients with a complete cytogenetic response (CCR) underwent bone marrow transplantation. Results Among 173 patients, the best response to treatment in patients treated with TKIs was CMR in 72, a major molecular response (MMR) in 84, CCR in 15, and refractory CML in 2. Currently, 22 have maintained CMR for 6 to 111 months after discontinuation of TKIs, and 19 (11%; 17 males, 2 females) have developed new onset of a malignancy. In these 19, the median age at the onset of cancer was 70 (31 – 85) years. Patients aged 60 years and older accounted for 15 (79%). The median period from the start of TKIs to the onset of cancer was 38 (10 – 117) months. Affected organs were bladder 5; stomach 3; rectum 3; large intestine 2; lung 2; and esophagus, appendix, prostate, and pancreas each in 1. The TKIs given to the patients with malignant diseases were IM alone in 13, IM → NI in 4, and IM → NI → DA in 2. Prior treatments included HU + IFN-α in 8 and IFN-α alone in 1. The observed number of patients who were diagnosed as malignant neoplasm was compared with the expected number. The expected number was obtained through integration of age specific incidence rate of malignant neoplasm from the start age taking medicine to the age at which the diagnosis as malignancy was made or the follow up was finished for censoring. The age specific incidence rates were estimated by interpolating five year old specific incidence rates from of the 2007's survey that was conducted by Center for Cancer Control and Information Services, National Cancer Center, Japan. The observed number/expected number (O/E) ratio for the occurrence of all malignant diseases was 1.00 (19/18.97), and the O/E for gastrointestinal cancer was 1.118 (11/9.84). Therefore, no increase in the incidence of malignant diseases was observed in patients treated with TKIs. However, the O/E for bladder cancer was 4.525 (5/1.11) with a 95% confidence interval of 1.42 – 9.32 (P = 0.0002), which means that the incidence of bladder cancer in patients treated with TKIs was higher than that in the general Japanese population. So far 19 patients have died and the median age at death was 79 (59 – 94) years. In these patients, 8 deaths were related to cancer and the others were caused by diseases associated with old age that were unrelated to the worsening of CML. Conclusion The introduction of TKIs has undoubtedly improved the prognosis of patients with CML. Based on the results of this investigation, the apparent increase in malignant diseases observed during the long-term follow-up of patients treated with TKIs was generally considered to be attributable to the aging of patients. We should however further investigate whether the higher incidence of bladder cancer seen in patients treated with TKIs is incidental or not. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 1544 Since myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are more prevalent in the elderly, intensive chemotherapy is difficult. However, recent progress in supportive therapy, especially with anti-fungal agents, and diagnostic procedures for invasive fungal infection (IFI) such as β-D glucan (β-D), galactomannan antigen (GM) and computed tomography (CT), have resulted in dramatically enhanced safety of post-chemotherapy control of elderly patients. To evaluate the efficacy and safety of our diagnosis and treatment strategy for IFI, we examined 112 consecutive episodes in 110 patients who received remission induction therapy from December 15, 2009 to June 18, 2011, including new or recurrent patients with MDS related AML (MDS-AML) and those with AML without a history of invasive aspergillosis (IA). Diagnosis was MDS-AML in 88 episodes (relapse 18) and AML in 24 (M1 5,M2 9,M4 9,M6 1).The median age was 70 (range: 21–88). Remission induction therapy consisted of behenoyl-ara-C for 10 days and idarubicin for 4 days (For further details, please refer to 51st ASH abstract #1052; Taiichi Kyo et al). Patients were always admitted to a clean room until neutrophil recovery, and were routinely administered macrophage-colony stimulating factor (CSF) and granulocyte-CSF. Amphotericin-b syrup and itraconazole capsules were given as antifungal prophylaxis. IFI diagnostic procedures consisted of CT, GM, β-D and surveillance culture (SC). At the time of admission a control CT was taken. CT was repeated within 24 hours when pyrexia of ≥38.0°C occurred. If fever showed no improvement, CT was repeated every 3 days (X-ray was also taken). If any change suggesting infection was noted, treatment against IA was considered. GM, β-D and SC were all conducted twice a week from the time of admission until discharge. ≥0.5 GM was regarded as positive and the treatment against IA was started even if there was only one positive result. At present there is no worldwide consensus concerning β-D, thus we considered a value exceeding the cut-off value of the reagent as positive. Treatment was started when there were both a positive result and increasing fever; and treatment against IA or candidiasis depended on imaging findings. Even if β-D was negative, candida detected by SC or diarrhea combined with increasing fever was also an indication for treatment against candidiasis. IA was treated with voriconazole (VRCZ) and candidiasis with micafungin (MCFG). VRCZ and MCFC were administered at 200–300 mg/twice/day and 100–300 mg/day, respectively. When no sufficient effect was observed with VRCZ alone, MCFG was added. Complete remission (CR) and partial remission (PR) were achieved in 81/112 (72%) and 9/112 (8%) episodes, while in 19/112 (17%) no response was obtained and 3/112 (2.7%) episodes resulted in death during chemotherapy. CR rate was comparable among de novo MDS-AML (49/70, 70%), MDS-AML relapse (9/18, 50%) and AML (23/24, 96%). The cause of death associated with chemotherapy was bacteremia 1, bacteremia or IA 1, and cerebral hemorrhage 1. GM was positive in 48 (43%) episodes. The reason for this large number was probably the advanced age of the patients and the long term neutropenia [absolute neutrophil count 2.5 indicates an unfavorable prognosis and 〉5.0 no hope of survival, none of our patients with GM 〉2.5 (10 patients) died of IA (2 died of other causes) and all patients with GM 〉5.0 (4 patients) survived. Candidemia was found in 2 patients (krusei 1, guilliermondii 1) and were treated succesfully. β-D was positive in 46 /112 (41%) episodes and 28/112 (25%) were also positive for GM. As for GM and β-D, GM positivity preceded that of β-D in 9/28 (32%); regarding GM and CT, GM positivity preceded the observation of CT findings in 13/30 (43%). At the beginning of this study, no control CT was obtained. But in the course of the study we found some patients who presented CT findings indicating IA, such as nodular lesions, but with no infection. Thus, we realized the need for a control CT to detect IA more accurately. Each diagnostic procedure has excellent characteristics but it is not sufficient by itself. The results of this single-center clinical study indicate that an improvement of antifungal therapy combined with a battery of diagnostic procedures may allow safe, intensive chemotherapy for many patients with MDS or AML. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 3604 Background: ATRA has improved treatment of APL and particularly made remission induction therapy easier. However, there is no post-remission therapy that can surely cure APL. As ATRA alone is unlikely to cure the disease, a new combination therapy that uses ATRA and can attain a high rate of cure is needed. Objective: To cure APL by a combination of intensive remission induction therapy and post-remission therapy with ATRA. Also, to give supportive therapy under careful monitoring to avoid death due to chemotherapy. Subjects and Methods: Sixty-five consecutive patients with previously untreated APL who visited our hospital between January 2000 and January 2011 were treated. The t (15;17) or PML-RARA translocation was observed respectively in chromosome analysis and genotyping in all patients. The age range was 16 to 79 (median: 51). Nineteen were aged 60 or older. Thirty-four and thirty-one were men and women, respectively. Remission induction therapy was started with ATRA at 45 mg/m2 (P.O.) immediately after diagnosis of APL. Idarubicin (IDR) at 10 mg/m2 (Days 1, 3, 5, and 7) and behenoyl-ara-C (BH-AC) at 350 mg/m2 (Days 1 through 7) were also administered. DIC was treated with continuous infusion of gabexate mesilate, platelet transfusion (to maintain a platelet count of ≥ 50,000/mm3), and frozen plasma transfusion (to maintain fibrinogen ≥ 100 mg/dL). The remission induction therapy was given in a sterile room. After completion of chemotherapy, macrophage colony-stimulating factor (M-CSF) was given for 10 days. Subsequently, granulocyte colony-stimulating factor (G-CSF) was administered until neutrophil recovery. After remission, the post-remission therapy commonly used in AML patients at our hospital (ASH, 2009, abstract, no. 1052) was given for 1 year. ATRA was given at 40 mg/body daily with chemotherapy. Patients received ATRA daily at the same dose for 3 years after completion of the post-remission therapy. The post-remission therapy involved high-dose-cytarabine (2 g/m2 BID for 5 days but 1 g/m2 × BID for 5 days for those aged 60 or older) combined with mitoxantrone (MIT) at 7 mg/m2/day for 3 days (HD-AC + MIT) given immediately after complete remission (CR). Subsequently, a combination of BH-AC at 350 mg/m2 × 4 + aclarubicin at 20 mg/body × 6 and another combination of BH-AC at 350 mg/m2 + IDR at 10 mg/m2 × 1 were given repeatedly in an alternating manner (35 days each). M-CSF (for 7 days) was administered followed by G-CSF after completion of each chemotherapy combination. Each patient was transferred to a sterile room when the WBC count decreased below 1,000. Results: CR was achieved in 63/65(97%). Early deaths (ED) occurred in 2/65 (aged 74 and 79) due to interstitial pneumonia. The follow-ups of patients lasted from 3 to 142 months (median: 74 months). Three patients have experienced a relapse of APL, and relapse of hematological malignancy (myelodysplastic syndrome [MDS]) was seen in 5 patients. A chromosomal aberration not observed at first visit was found at relapse in all 5 patients who developed MDS. Six patients have died from relapsed APL (2), MDS (2), pneumonia following HD-AC + MIT (1), or liver cancer (1). For 63 patients who achieved CR, the overall survival (OS) calculated by the Kaplan-Meier method was 87% at 13 years. The disease-free survival (DFS) was 82% at 13 years. The OS and DFS for patients younger than 60 were respectively 93% and 80%. They were respectively 78% and 87% for patients aged 60 or older, showing no difference between the age groups. The DFS was 83% and 80% for patients treated with HDAC (52) and not treated with HDAC (11), respectively, showing little difference. When analyzed using the risk-based prognostic system of Sanz, et al., the OS was 70, 87, and 100% respectively for patients classified into the low (18), intermediate (27), and high risk (18) groups. The DFS was 72, 81, 94%, respectively. The analysis showed the best results for the high-risk group. Discussion: ATRA + intensive chemotherapy and long-term ATRA can attain a high rate of long-term survival (cure) for patients with APL regardless of age and risk group. Despite the use of intensive chemotherapy, only one patient died due to chemotherapy. This seems to be due to the selection of appropriate supportive therapy. Early diagnosis and bone marrow transplantation in patients with relapse (MDS) may further improve the rate of cure in patients with APL. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 1503 (Objective) The treatment outcome of patients with Ph+ ALL has significantly improved since the advent of TKIs such as imatinib and dasatinib. However, the long-term survival of these patients is not necessarily high when bone marrow transplantation (BMT) is not performed. The present study was aimed at developing an effective combination of a TKI and chemotherapy for long-term survival of patients with Ph+ ALL but ineligible for BMT. (Subjects and Methods) Forty-three consecutive patients (18 men, 25 women) with previously untreated Ph+ ALL who visited our hospital between June 2001 and February 2011 were treated. The age range was 13 to 84 years (median: 57), and 21 were 60 years or older. Measurement of BCR-ABL fusion transcript levels was performed immediately in these patients, and imatinib (IM) was started at 600 mg/body/day (given daily as a rule) as soon as the patient tested positive. A remission induction regimen (chemotherapy) used commonly in acute myeloblastic leukemia (AML) patients at our hospital was combined with TKIs in the first 14 patients. Another remission induction regimen often used in ALL patients at our hospital was then combined with TKIs in the subsequent 29 patients. The AML remission induction regimen used idarubicin (IDR) at 12 mg/m2 for 4 days, behenoyl-ara-C (BH-AC) at 350 mg/m2 for 10 days, and prednisolone (PSL) at 40 mg/body (P.O.) for 10 days. PSL was initially given at 100 mg/body (P.O.) and then gradually reduced in the ALL remission induction regimen. Vincristine (VCR) at 1.3 mg/m2 (Days 1, 8, 15, and 22), daunorubicin at 60 mg/m2 (Days 1, 2, and 3), cyclophosphamide at 1200 mg/m2 (Day 2), and L-asparaginase at 3000 μ/m2 (Days 11, 13, 16, 18, and 20) were administered. The remission induction therapies were given in a sterile room. Macrophage colony-stimulating factor was given for 7 days from Day 11 and granulocyte colony-simulating factor from Day 19. A post-remission therapy commonly administered to AML patients at our hospital was given after remission for 1 year (ASH, 2009, abstract, no. 1052). High-dose cytarabine (at 2 g/m2 BID for 5 days but at 1 g/m2 BID in patients aged 60 years or older) (HD-AC) and mitoxantrone (MIT) at 7 mg/m2 × 3 were initially administered after remission. Maintenance/consolidation therapy was given by alternating BH-AC at 350 mg/m2 × 4 + aclarubicin at 20 mg/body × 6 and BH-AC at 350 mg/m2 × 4 + IDR at 10 mg/m2 × 1 + VCR at 1.3 mg/m2 (each for 35 days). IM was given daily at 600 mg/day simultaneously with the post-remission therapy. Dasatinib was used in the post-remission therapy of 8 patients at 140 mg/day. All of the TKIs were given to patients for 3 years after completion of chemotherapy. (Results) Complete remission (CR) was achieved in 41/43 (95%). CR was achieved in 13 out of 14 (93%) patients treated with the AML regimen and 28 out of 29 (97%) treated with the ALL regimen. DIC occurred in 31/41 (76%) during remission induction therapy. The follow-ups of patients achieving CR lasted for 5 to 128 months (median: 24 months). Ten patients (aged 25 to 54 years [median: 37]) underwent BMT at first CR. Thirty-one patients (aged 13 to 84 years [median: 63]) were assigned to the chemotherapy group. The 10-year overall survival (OS) calculated by the Kaplan-Meier method was 57% for 41 patients who achieved CR, 66% for 20 patients younger than 60 years, and 49% for 21 patients aged 60 years or older. The OS was 80% for 10 patients who underwent BMT at first CR and 47% for 31 patients in the chemotherapy group. The 50% OS of the chemotherapy group was 36 months. The 10-year event-free survival (EFS) was 50% for patients who achieved CR, 80% for patients who underwent BMT at first CR, and 43% for the chemotherapy group. The 50% EFS of the chemotherapy group was 33 months. Fifteen patients have relapsed, and a new chromosomal aberration was observed at relapse in 11/13 (85%). (Discussion) The results of the present report indicate that BMT is the first choice for post-remission therapy of Ph+ ALL. Fifty percent of patients aged 60 years or older, who account for about half of the patients with Ph+ ALL, have achieved long-term survival with the prolonged TKI + chemotherapy used in the present report. Relapse was also rare among patients who received the combination and maintained CR for 3 years or longer. A combination of an appropriate TKI and a chemotherapy regimen as well as careful monitoring for complications is likely to further extend the survival of patients with Ph+ ALL. Disclosures: No relevant conflicts of interest to declare.