[Granulocyte-colony stimulating factor-producing multiple myeloma presenting with neutrophilia].

A 71-year-old woman complained of nausea and anorexia. Laboratory tests revealed significant neutrophilia and immunoglobulin A-kappa type M proteinemia, as well as increased plasma cells on bone marrow examination. Furthermore, the serum granulocyte-colony stimulating factor (G-CSF) concentration was high at 160 pg/ml, and the colony stimulating factor 3 receptor (CSF3R)-T618I mutation was negative. Immunohistochemical (IHC) analysis of bone marrow specimens using the anti-G-CSF antibody revealed immunopositivity of some myeloma cells. The patient was diagnosed using G-CSF-producing myeloma and was treated with daratumumab, lenalidomide, and dexamethasone. Her treatment resulted in a very good partial response, with normalization of both serum G-CSF levels and neutrophil count. There have been a few cases of G-CSF -producing myeloma reported, and it has previously been reported as chronic neutrophilic leukemia with M proteinemia. According to previous reports, techniques such as serum G-CSF measurements, IHC with an anti-G-CSF antibody, and CSF3R gene mutation analysis are useful for differentiating G-CSF-producing myeloma. However, the clinical characteristics and long-term prognosis of G-CSF-producing myeloma remain unknown. Additional case gathering and investigations are required.

JAK2 V617F Mutation and Large Cerebral Artery Disease in Patients with Myeloproliferative Neoplasms.

AIM: The aim of the present study was to clarify the association between the Janus kinase 2 (JAK2) V617F mutation and large cerebral artery disease (LCAD) in patients with myeloproliferative neoplasms (MPNs). METHODS: We retrospectively analysed patients diagnosed with MPNs between June 1992 and June 2022 who underwent brain magnetic resonance imaging. LCAD was defined as extracranial or intracranial large artery stenosis (≥ 50%) or occlusion on magnetic resonance angiography. RESULTS: A total of 86 patients (47 males; median age, 69 years old) were enrolled in this study. JAK2 V617F mutation was detected in 63 (73.3%) patients and LCAD in 35 (40.7%) patients. Univariate analysis showed that history of ischaemic stroke (LCAD, 62.9% vs. non-LCAD, 11.8%; P＜0.001), JAK2 V617F mutation (91.4% vs. 60.8%, P=0.002), and age ≥ 60 years (85.7% vs. 60.8%, P=0.016) were significantly associated with LCAD. Multiple logistic regression analysis showed that, in addition to ischaemic stroke, age ≥ 60 years and diabetes mellitus, JAK2 V617F mutation (odds ratio 29.2, 95% confidence interval 1.2-709.8, P=0.038) was independently associated with LCAD. LCAD was frequently observed in the intracranial carotid (14/35, 40.0%) and middle cerebral (13/35, 37.1%) arteries. CONCLUSIONS: This study revealed a significant association between the JAK2 V617F mutation and LCAD in patients with MPNs. This suggests that the JAK2 V617F mutation may promote cerebrovascular atherosclerosis and could be very important in determining therapeutic strategies for patients with not only JAK2 V617F-mutated MPNs but also LCAD-related stroke.

Clinical characteristics of Japanese patients with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis.

Myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) is a rare disease, which presents with features of myelodysplastic syndromes with ring sideroblasts and essential thrombocythemia, as well as anemia and marked thrombocytosis. SF3B1 and JAK2 mutations are often found in patients, and are associated with their specific clinical features. This study was a retrospective analysis of 34 Japanese patients with MDS/MPN-RS-T. Median age at diagnosis was 77 (range, 51-88) years, and patients had anemia (median hemoglobin: 9.0 g/dL) and thrombocytosis (median platelet count: 642 × 109/L). Median overall survival was 70 (95% confidence interval: 68-not applicable) months during the median follow-up period of 26 (range: 0-91) months. A JAK2V617F mutation was detected in 46.2% (n = 12) of analyzed patients (n = 26), while an SF3B1 mutation was detected in 87.5% (n = 7) of analyzed patients (n = 8). Like those with myelodysplastic syndromes or myeloproliferative neoplasms, patients often received erythropoiesis-stimulating agents and aspirin to improve anemia and prevent thrombosis. This study, which was the largest to describe the real-world characteristics of Japanese patients with MDS/MPN-RS-T, showed that the patients had similar characteristics to those in western countries.

[Evaluation of the correlation between JAK2V617F allele burden by Quenching Probe-Tm method and allele-specific quantitative PCR method].

The JAK2V617F mutation is a driver mutation of myeloproliferative neoplasms (MPNs). V617F allele burden is considered a risk factor for complications associated with MPNs and is a predictor of prognosis. In Japan, V617F allele burden has been measured in laboratory settings using the i-densyTM IS-5320 genetic analyzer with the quenching probe-Tm (QP-Tm) method. However, since 2020, allele-specific quantitative PCR (AS-qPCR) is being performed in clinical settings for measuring V617F allele burden. To investigate the clinical usefulness of the QP-Tm method in patients with MPNs, we evaluated the V617F allele burden measured by both the methods. A good correlation was observed between the V617F allele burden determined using QP-Tm and that determined using AS-qPCR (P<0.001, rs=0.952). The median mutant allele burden, as determined using the QP-Tm method, was significantly higher in patients with polycythemia vera than in those with essential thrombocythemia. The results of this study suggested that the QP-Tm method will continue to be useful clinical ancillary test for measuring V617F allele burden.

Successful treatment with ABL tyrosine kinase inhibitor for patients with acute myeloid leukemia with BCR-ABL1.

Acute myeloid leukemia (AML) with BCR-ABL1 is rare and has a poor prognosis with conventional chemotherapy or ABL tyrosine kinase inhibitors (TKIs) alone. We reported a case of AML with BCR-ABL1 patient who was successfully treated with dasatinib alone; additionally, we previously reported another case of long-term remission maintained with imatinib monotherapy. These results suggested that a treatment with a novel and significantly potent TKI may be effective in AML with BCR-ABL1 patients with low tumor burden and without additional chromosome aberrations and ABL kinase domain mutations.

Comparison of starting doses of anagrelide as a first-line therapy in patients with cytoreductive therapy-naïve essential thrombocythemia: difference between starting at 0.5 and 1.0 mg/day.

Anagrelide is widely used for cytoreductive therapy in patients with essential thrombocythemia who are at high risk for thrombosis. The recommended starting dose in the package insert of anagrelide varies by country. A high starting dose leads to an early onset of action, but causes a higher incidence of adverse events. This relationship indicates that both the onset of action and side effects of anagrelide are dose dependent. We retrospectively compared the efficacy and safety of anagrelide as a first-line drug between patients with essential thrombocythemia who started at 0.5 or 1.0 mg/day. Incidence of total adverse events and anagrelide-related palpitation, discontinuation rates, and the median daily dose of anagrelide were lower in the 0.5 mg/day group than in the 1.0 mg/day group; however, comparable platelet-lowering effects were achieved in both groups. These data suggest that a low starting dose of anagrelide followed by dose escalation may result in fewer adverse events and lower discontinuation rates, while providing desirable platelet-lowering effects. Initiating anagrelide at a lower dose may be a useful approach in actual clinical practice.

Jumping translocations of 1q in donor cell-derived myelodysplastic syndrome after cord blood transplantation: Case report and review of the literature.

Donor cell-derived leukemia and myelodysplastic syndrome (DCL) is a rare complication in patients after allogenic stem cell transplantation (SCT). Since 1971, numerous cases of DCL have been reported, but the detailed mechanisms of DCL are still unclear. A patient with jumping translocations (JTs) of 1q in umbilical cord blood donor cell-derived myelodysplastic syndrome (MDS), which likely occurred due to genetic alterations of TET2 and ASXL1 after cord blood transplantation (CBT), was examined in this study. Previously reported DCL cases after CBT that focused on the cytogenetic and molecular characteristics of these patients and patient outcome were reviewed. A total of 30 cases of DCL after CBT were identified between 2005 and 2018. The median time from CBT to the development of DCL was 16 months. The number of patients with DCL who were diagnosed with acute myeloid leukemia (AML) and MDS was 19 and 8, respectively. JTs were frequently observed in 5 of 27 DCL patients who had cytogenetic abnormalities, including our patient. Molecular abnormalities were described in 7 of the cases, and the most frequent abnormality was an NPM1 mutation. Other gene mutations that were usually found in de novo MDS or AML were observed in JT-DCL after CBT. From these results, chromosomal abnormalities such as JTs that occur subsequent to genetic alterations were seemed an important mechanisms underlying DCL onset in patients after CBT. Further molecular analyses regarding the genetic alterations of JTs are required to understand the pathogenesis of umbilical cord blood-derived JT-DCL.

[Relationship between Coombs-positive autoimmune hemolytic anemia and development of malignant tumors: a retrospective study].

Autoimmune hemolytic anemia (AIHA) is secondary to underlying diseases, such as autoimmune diseases and lymphoid malignancies. Recently, solid cancers have also been reported to be associated with AIHA, although there is not much information available. In this study, we retrospectively examined the correlation between AIHA and onset of malignancy in 100 patients diagnosed with AIHA based on the broad definition of AIHA at our hospital and cooperating institutions from January 1, 1995 to May 31, 2016. Malignancies were detected in 52 of the 100 patients (hematological malignancies: 39 patients; solid cancers: 22 patients; total malignancies including multiple primary malignancies: 67 patients). Of the 67 patients with malignancies, 28 were diagnosed with malignancies within 6 months of AIHA diagnosis. All patients with cold agglutinin disease (CAD) were associated with malignancies. Compared with warm AIHA, solid cancers were significantly more common among the patients with CAD. These findings emphasize the importance of investigating the malignancies upon diagnosis of AIHA.

[Concurrent CALR and SF3B1 gene mutations in a patient with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis].

A 83-year-old female patient was admitted to our hospital due to hematological manifestation of juvenile granulocytes and macrocytic anemia. Bone marrow (BM) examination revealed erythroid dysplasia and cytoplasmic blasts, and hence the patient was diagnosed with myelodysplastic syndrome with ring sideroblasts and with single lineage dysplasia (MDS-RS-SLD). Erythrocyte transfusion was performed as a supportive therapy, and there was a gradual increase in the number of blood cells. Therefore, BM re-examination was performed and it was confirmed that the number of megakaryocytes increased, so the patient's condition was determined as myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis (MDS/MPN with RS-T). Incidentally, gene mutation analysis showed CALR gene mutation. Thereafter, administration of hydroxycarbamide and anagrelide did not show adverse events and complications, and a good blood count control was obtained. Furthermore, it was also confirmed that an SF3B1 gene mutation is highly positive in MDS-RS. There was no report on CALR-mutant MDS/MPN in Japan, and it is a rare disease overseas.

Efficacy and safety of anagrelide as a first-line drug in cytoreductive treatment-naïve essential thrombocythemia patients in a real-world setting.

OBJECTIVE: This study aimed to retrospectively assess the efficacy and safety of anagrelide in cytoreduction therapy-naïve essential thrombocythemia (ET) patients in a real-world setting. METHOD: Data from 53 ET patients who received anagrelide as a first-line therapy were reviewed for patient characteristics, antiplatelet status, cytoreduction status, therapeutic effects, adverse events, thrombohemorrhagic event development, progression to myelofibrosis or acute leukemia, and cause of death. RESULTS: The rate of achieving a platelet count of <600 × 109 /L during anagrelide monotherapy was 83.0%. Adverse events occurred in 32 of 53 patients, and tended to be slightly more severe in patients with cardiac failure; however, they were mostly tolerable. The therapeutic effect of anagrelide was consistent, regardless of genetic mutation profiles. The incidence of anemia as an adverse event was significantly higher in the CALR mutation-positive group. Favorable platelet counts were also achieved in patients for whom hydroxyurea was introduced as a replacement for anagrelide or in addition to anagrelide because of unresponsiveness or intolerance to treatment. CONCLUSION: In Japanese cytoreduction therapy-naïve ET patients, anagrelide administration as a first-line therapy demonstrated favorable effects in reducing platelet counts, and its safety profile that was generally consistent with those in previous reports.

Successful Cord Blood Transplantation in a Werner Syndrome Patient with High-risk Myelodysplastic Syndrome.

Werner syndrome (WS) confers a high risk of the development of neoplasias, including hematological malignancies, and curative treatment for these malignancies is difficult to achieve. A 44-year-old man with myelodysplastic syndrome was admitted to our hospital. He was diagnosed with mutation-proven WS. He underwent cord blood transplantation (CBT) following fludarabine, busulfan, and melphalan administration. A chimerism analysis of his marrow blood on day 62 showed a donor pattern >95%, which confirmed engraftment. The patient lived for 15 months while maintaining remission of MDS without treatment-related toxicity. Our case shows that CBT can be a treatment modality for WS patients with hematological malignancies.

Efficacy of prophylactic irradiation to the contralateral testis for patients with advanced-stage primary testicular lymphoma: an analysis of outcomes at a single institution.

BACKGROUND: Primary testicular lymphoma (PTL) is a rare, extranodal lymphoma that often relapses in the contralateral testis. We evaluated outcomes in patients with any stage of PTL who had received CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) with rituximab chemotherapy and prophylactic radiotherapy to the contralateral testis. METHODS: We retrospectively identified 15 patients (median age 66 years; range 39-81) diagnosed with diffuse large B-cell PTL in the period 2000-2014. Characteristics and outcomes of these cases were evaluated. RESULTS: All patients received initial orchiectomy followed by CHOP with or without rituximab. Thirteen patients received prophylactic irradiation to the contralateral testis. During follow-up (median 67 months; range 8-190), one patient died of PTL, three died of other disease, and nine were free from relapse. For stage I-II disease, 5-year progression-free and overall survival rates were 80 and 100%, respectively. For stage III-IV PTL, 5-year progression-free and overall survival rates were 50 and 72%, respectively. Notably, no patient developed contralateral testicular involvement after prophylactic irradiation. CONCLUSIONS: The observed outcomes suggest that the combination of (i) CHOP plus rituximab and (ii) radiotherapy for local recurrence prophylaxis is promising for both stage I-II and stage III-IV PTL.

Methotrexate-associated primary hepatic malignant lymphoma following hepatectomy: A case report.

INTRODUCTION: Recently, immunosuppressant-associated malignant lymphoma (ML) cases have been increasing along with the development of several effective immunosuppressant drugs for rheumatoid arthritis (RA). Among methotrexate (MTX)-associated lymphoproliferative disorders, primary hepatic lymphoma (PHL) in patients with RA following surgical resection has not been reported previously. PRESENTATION OF CASE: A 65-year-old woman who is a hepatitis B virus carrier with a history of RA was admitted. MTX was introduced seven years prior as an RA treatment. Her laboratory data showed no elevation of several tumor markers, and liver function test results were normal. On contrasted computed tomography (CT) scanning, a slightly enhanced tumor was detected at the early phase, and tumor staining was sustained at the delayed phase. Further, subsegmentectomy of the S6 was performed. The pathological diagnosis was diffuse large B-cell lymphoma. However, positron emission tomography-CT and bone marrow aspiration sample showed no resident sign of ML. DISCUSSION: Diagnosis of PHL before surgery is difficult. If the mass lesion was solitary and had a certain degree of size, then resection could be performed for its treatment and diagnosis. The treatment for ML requires a diagnosis of the subtypes to select a therapeutic agent and determine the prognosis. Once a precise preoperative diagnosis was made, withdrawing MTX could be the first treatment in case of MTX-related ML. CONCLUSION: Long-term usage of immunosuppressant drugs could cause proliferative ML. Considering the increasing occurrence of MTX-related ML, withdrawing MTX should be considered, especially in patients with long-term immunosuppressant usage for RA.

Low neutrophil alkaline phosphatase score is a new aspect of calreticulin-mutated myeloproliferative neoplasms.

Calreticulin (CALR) and JAK2-V617F gene mutations, which are major genetic mutations in patients with primary myelofibrosis (PMF) and essential thrombocythemia (ET), exert different effects on the clinical features and outcomes of these diseases. We analyzed 88 and 9 patients with ET and PMF, respectively, and determined the differences in the clinical characteristics of ET patients with JAK2-V617F compared with CALR mutations. The frequency of the JAK2-V617F and CALR mutations were 64 and 22 %, respectively. Patients with CALR mutations were younger, had a lower white blood cell count, and had a lower rate of thrombotic events than patients with the JAK2 mutation. The neutrophil alkaline phosphatase (NAP) score of 16 patients with CALR mutations was significantly lower than the normal controls, which was mainly due to the high proportion of NAP-negative neutrophils. This is the first report to show an association between CALR mutations in patients with myeloproliferative neoplasms (MPN) and the NAP score. Although the mechanism is unclear, the NAP score could be a useful and reliable biochemical marker to discriminate the mutational status of MPN patients. Further investigation is warranted to determine whether these characteristics contribute to the pathogenesis of MPN and the NAP score.

Withaferin A suppresses the growth of myelodysplasia and leukemia cell lines by inhibiting cell cycle progression.

Treatment outcomes for acute myeloid leukemia and myelodysplastic syndromes (MDS) remain unsatisfactory despite progress in various types of chemotherapy and hematopoietic stem cell transplantation. Therefore, there is a need for the development of new treatment options. We investigated the growth-suppressive effects of withaferin A (WA), a natural plant steroidal lactone, on myelodysplasia and leukemia cell lines. WA exhibited growth-suppressive effects on the cell lines, MDS-L, HL-60, THP-1, Jurkat and Ramos, and induction of cell cycle arrest at G2/M phase at relatively low doses. Evaluation by annexin V/PI also confirmed the induction of partial apoptosis. Gene expression profiling and subsequent gene set enrichment analysis revealed increased expression of heme oxygenase-1 (HMOX1). HMOX1 is known to induce autophagy during anticancer chemotherapy and is considered to be involved in the treatment resistance. Our study indicated increased HMOX1 protein levels and simultaneous increases in the autophagy-related protein LC3A/B in MDS-L cells treated with WA, suggesting increased autophagy. Combined use of WA with chloroquine, an autophagy inhibitor, enhanced early apoptosis and growth suppression. Together with the knowledge that WA had no apparent suppressive effect on the growth of human normal bone marrow CD34-positive cells in the short-term culture, this drug may have a potential for a novel therapeutic approach to the treatment of leukemia or MDS.

[Correlation between serum L-carnitine concentration and neutrophil engraftment in patients treated with cord blood transplantation].

In cord blood transplantation (CBT), the amount of time elapsing until hematological engraftment has effects on the transplantation results. Carnitine deficiency has been reported to cause erythropoietin refractory anemia in chronic hemodialysis patients and thrombocytopenia or leukopenia of cirrhosis, and carnitine supplementation can improve hematopoiesis in patients with hepatic or renal failure. Patients who receive CBT may suffer from carnitine deficiency, but no studies have investigated the carnitine status of such patients. Herein, we determined the concentration of free carnitine (FC) and investigated the correlation between FC and engraftment in patients who received CBT. Twenty-three patients who received CBT at our hospital during the period from April 2013 to January 2015 were enrolled in this study. One patient was excluded because of graft failure, such that 22 patients were ultimately evaluable. FC concentrations of the patients were sequentially monitored at 4 time points (before conditioning therapy, day 0, day 7, and day 14), basic laboratory data were collected, and their correlations with engraftment were analyzed. FC concentrations of the patients were generally low (before conditioning therapy: 33.1, day 0: 43.2, day 7: 38.3, and day 14: 37.8 µmol/l). Significant inverse correlations were observed between FC concentrations and the number of days required for neutrophil engraftment on day 0 and day 14 (before conditioning therapy: P=0.15, r=-0.33, day 0: P=0.04, r=-0.43, day 7: P=0.30, r=-0.23, and day 14: P=0.01, r=-0.55). These results suggest carnitine to be an important nutrient that promotes hematopoietic recovery after CBT.

Five-aza-2'-deoxycytidine-induced hypomethylation of cholesterol 25-hydroxylase gene is responsible for cell death of myelodysplasia/leukemia cells.

DNA methyltransferase inhibitors (DNMT inhibitors) are administered for high-risk MDS, but their action mechanisms are not fully understood. Hence, we performed a genome-wide DNA methylation assay and focused on cholesterol 25-hydroxylase (CH25H) among the genes whose expression was up-regulated and whose promoter region was hypomethylated after decitabine (DAC) treatment in vitro. CH25H catalyzes hydroxylation of cholesterol and produces 25-hydroxycholesterol (25-OHC). Although CH25H mRNA expression level was originally low in MDS/leukemia cell lines, exposure to DNMT inhibitors enhanced CH25H mRNA expression. The promoter region of CH25H was originally hypermethylated in HL-60 and MDS-L cells, but DAC treatment induced their hypomethylation together with increased CH25H mRNA expression, activation of CH25H-oxysterol pathway, 25-OHC production and apoptotic cell death. We further confirmed that normal CD34-positive cells revealed hypomethylated status of the promoter region of CH25H gene. CH25H-knockdown by transfection of shRNA lentiviral vector into the cell lines partially protected the cells from DAC-induced cell death. Exogenous addition of 25-OHC suppressed leukemic cell growth. The present study raises a possibility that DNMT inhibitors activate CH25H-oxysterol pathway by their hypomethylating mechanism and induce leukemic cell death. Further investigations of the promoter analysis of CH25H gene and therapeutic effects of DNMT inhibitors on MDS/leukemia will be warranted.

Philadelphia chromosome-positive acute lymphoblastic leukemia with extramedullary and meningeal relapse after allogeneic hematopoietic stem cell transplantation that was successfully treated with dasatinib.

Central nervous system (CNS) relapse is a critical issue while treating Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). A 58-year-old woman with Ph-positive ALL who relapsed after bone marrow transplantation for meningeal leukemia was treated with high-dose methotrexate, which resulted in remission. She underwent allogeneic cord blood transplantation followed by reduced intensity conditioning chemotherapy with imatinib; however, she experienced CNS relapse and developed an extramedullary mass on the right side of the temporal region. We treated 40 mg of dasatinib once daily, which had to be temporarily discontinued because she developed grade 2 pleural effusion and grade 2 hematemesis. After reinitiation of dasatinib, the extramedullary mass disappeared and meningeal leukemia ameliorated almost immediately. With 40 mg dasatinib administered once daily, its trough level and cerebrospinal fluid (CSF) concentration were 32 ng/mL and below the sensitivity threshold of 1 ng/mL, respectively. Treatment was continued, and the patient remained in complete remission until she died of pneumonia 7 years after the initial diagnosis of ALL. Dasatinib can be an effective treatment for Ph-positive ALL with CNS relapse. Although the concentration in the CSF seems low, it may be sufficient to exert anti-leukemic effects in the human CNS.

Mutation patterns of 16 genes in primary and secondary acute myeloid leukemia (AML) with normal cytogenetics.

Acute myeloid leukemia patients with normal cytogenetics (CN-AML) account for almost half of AML cases. We aimed to study the frequency and relationship of a wide range of genes previously reported as mutated in AML (ASXL1, NPM1, FLT3, TET2, IDH1/2, RUNX1, DNMT3A, NRAS, JAK2, WT1, CBL, SF3B1, TP53, KRAS and MPL) in a series of 84 CN-AML cases. The most frequently mutated genes in primary cases were NPM1 (60.8%) and FLT3 (50.0%), and in secondary cases ASXL1 (48.5%) and TET2 (30.3%). We showed that 85% of CN-AML patients have mutations in at least one of ASXL1, NPM1, FLT3, TET2, IDH1/2 and/or RUNX1. Serial samples from 19 MDS/CMML cases that progressed to AML were analyzed for ASXL1/TET2/IDH1/2 mutations; seventeen cases presented mutations of at least one of these genes. However, there was no consistent pattern in mutation acquisition during disease progression. This report concerns the analysis of the largest number of gene mutations in CN-AML studied to date, and provides insight into the mutational profile of CN-AML.

Philadelphia chromosome-positive acute myeloid leukemia (Ph + AML) treated with imatinib mesylate (IM): a report with IM plasma concentration and bcr-abl transcripts.

We studied the efficacy and pharmacokinetics of imatinib mesylate (IM) and bcr-abl expression in a Philadelphia chromosome-positive acute myeloid leukemia (Ph + AML) patient, a rare disease with a poor prognosis. Although sufficient IM trough concentrations were maintained, bcr-abl transcripts revealed only one-log reduction with IM monotherapy, suggesting a resistance against IM, and this patient required additional chemotherapy. Despite the resistance against IM at induction therapy, the patient has been in complete molecular response for more than 6 months with IM maintenance monotherapy. Our experience suggests that IM might have a positive role in consolidation and/or maintenance therapy in remission Ph + AML patients.