Treatment and survival among 1594 patients with ATL.

Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature T lymphocytes caused by human T-lymphotropic virus type I. Intensive combination chemotherapy and allogeneic hematopoietic stem cell transplantation have been introduced since the previous Japanese nationwide survey was performed in the late 1980s. In this study, we delineated the current features and management of ATL in Japan. The clinical data were collected retrospectively from the medical records of patients diagnosed with ATL between 2000 and 2009, and a total of 1665 patients' records were submitted to the central office from 84 institutions in Japan. Seventy-one patients were excluded; 895, 355, 187, and 157 patients with acute, lymphoma, chronic, and smoldering types, respectively, remained. The median survival times were 8.3, 10.6, 31.5, and 55.0 months, and 4-year overall survival (OS) rates were 11%, 16%, 36%, and 52%, respectively, for acute, lymphoma, chronic, and smoldering types. The number of patients with allogeneic hematopoietic stem cell transplantation was 227, and their median survival time and OS at 4 years after allogeneic hematopoietic stem cell transplantation was 5.9 months and 26%, respectively. This study revealed that the prognoses of the patients with acute and lymphoma types were still unsatisfactory, despite the recent progress in treatment modalities, but an improvement of 4-year OS was observed in comparison with the previous survey. Of note, one-quarter of patients who could undergo transplantation experienced long survival. It is also noted that the prognosis of the smoldering type was worse than expected.

Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: a randomized phase II study.

This multicentre, randomized, phase II study was conducted to examine whether the addition of mogamulizumab, a humanized anti-CC chemokine receptor 4 antibody, to mLSG15, a dose-intensified chemotherapy, further increases efficacy without compromising safety of patients with newly diagnosed aggressive adult T-cell leukaemia-lymphoma (ATL). Patients were assigned 1:1 to receive mLSG15 plus mogamulizumab or mLSG15 alone. The primary endpoint was the complete response rate (%CR); secondary endpoints included the overall response rate (ORR) and safety. The %CR and ORR in the mLSG15-plus-mogamulizumab arm (n = 29) were 52% [95% confidence interval (CI), 33-71%] and 86%, respectively; the corresponding values in the mLSG15 arm (n = 24) were 33% (95% CI, 16-55%) and 75%, respectively. Grade ≥ 3 treatment-emergent adverse events, including anaemia, thrombocytopenia, lymphopenia, leucopenia and decreased appetite, were observed more frequently (≥10% difference) in the mLSG15-plus-mogamulizumab arm. Several adverse events, including skin disorders, cytomegalovirus infection, pyrexia, hyperglycaemia and interstitial lung disease, were observed only in the mLSG15-plus-mogamulizumab arm. Although the combination strategy showed a potentially less favourable safety profile, a higher %CR was achieved, providing the basis for further investigation of this novel treatment for newly diagnosed aggressive ATL. This study was registered at ClinicalTrials.gov, identifier: NCT01173887.

Development of acquired hemophilia A during treatment of multiple myeloma with lenalidomide.

We describe a 67-year-old female demonstrating symptomatic multiple myeloma (MM) with anemia and bone lesions initially diagnosed in 2009. Although a partial response was achieved after bortezomib and dexamethasone treatment, MM recurred in 2012. Therefore, treatment with lenalidomide, cyclophosphamide, and dexamethasone was commenced. Coagulation tests conducted prior to the chemotherapy were normal. Lenalidomide was discontinued after 10 days due to exacerbation of renal dysfunction. Simultaneously, activated partial thromboplastin time (APTT) was prolonged to 89.5 seconds. The mixing test showed an inhibitor pattern, with factor VIII at 2% and factor VIII inhibitor at 4.85 BU/ml. A diagnosis of acquired hemophilia A was made, and treatment with prednisolone was started, after which APTT improved to 36.4 seconds and factor VIII inhibitor decreased to 1.09 BU/ml. The factor VIII inhibitor level again increased concomitantly with restarting lenalidomide, which was, therefore, discontinued, while immunosuppressive therapy was administered with the addition of cyclophosphamide. Factor VIII inhibitor gradually disappeared from the patient's blood over the next four months. To the best of our knowledge, this is the first description of lenalidomide as a possible cause of acquired hemophilia A. Our experience indicates that we need to pay attention to acquired hemophilia A after initiating lenalidomide therapy in patients with hematologic malignancies.

Retrospective analysis of prognostic factors for angioimmunoblastic T-cell lymphoma: a multicenter cooperative study in Japan.

Angioimmunoblastic T-cell lymphoma (AITL) is a major type of peripheral T-cell lymphoma (PTCL). To elucidate the clinicopathologic characteristics and prognosis of AITL in Japan, we retrospectively analyzed 207 patients with AITL. The median patient age was 67 years (range, 34-91 years), with 73% of patients older than 60 years. With a median follow-up of 42 months in surviving patients, 3-year overall survival (OS) was 54% and progression-free survival (PFS) was 38%. The International Prognostic Index (IPI) and the prognostic index for PTCL, not otherwise specified (PIT) were predictive for OS in this analysis. Multivariate analysis found that age older than 60 years, elevated white blood cell (WBC) and IgA levels, the presence of anemia and thrombocytopenia, and extranodal involvement at > 1 site were significant prognostic factors for OS, and IgA, anemia, and mediastinal lymphadenopathy were significant prognostic factors for PFS. A novel prognostic model consisting of the prognostic factors for OS was successfully constructed. In conclusion, IPI and PIT were still useful for prognostication of AITL, and other factors, including those not used in IPI, such as IgA, anemia, WBC count, thrombocytopenia, and mediastinal lymphadenopathy, also significantly affected prognosis. Future investigations for IgA as a unique prognostic factor are warranted.

[Successful treatment with high-dose methotrexate/cytarabine regimen in a patient in SMILE regimen-resistant extranodal natural killer/T-cell lymphoma].

A 28-year-old man complained of pain in the oral mucosa and pharynx in March 2011, and then developed fever and generalized swelling of the cheek. In March 2012, a gum biopsy led to a diagnosis of extranodal natural killer/T-cell lymphoma (ENKL). (18)F-FDG-PET revealed significant uptake in the mouth, tonsils, jawbone, shoulder blade, humerus, ilium, femur, and spleen. After two courses of the SMILE (dexamethasone, methotrexate (MTX), ifosfamide, L-asparaginase, etoposide) regimen, the response was stable disease. However, a high-dose MTX/cytarabine (MA) regimen was effective. After three courses of the MA regimen, a partial response was achieved. Then, allogeneic bone marrow transplantation from an unrelated donor was performed. At 10 months after transplantation, there was no sign of recurrence. Although the optimal treatment for ENKL refractory to the SMILE regimen has yet to be established, our case suggests the MA regimen to be a potentially effective treatment option.

Characteristics of chronic lymphocytic leukemia in Japan: Comprehensive analysis of the CLLRSG-01 study.

Chronic lymphocytic leukemia (CLL) is rare in Japan. We conducted the nationwide, prospective observational study CLLRSG-01 to clarify the current state of CLL in Japan and to make accurate international comparisons by preparing naturally air-dried smears like those used in other countries. Of the 201 untreated patients enrolled and evaluated, 119 were diagnosed with CLL and 82 with non-CLL mature B-cell neoplasms, based on the WHO classification. Of the 119 CLL patients, 90 were classified as typical and 29 as atypical according to FAB classification morphology, with the proportion of atypical CLL consistent with reports from other countries. Immunophenotypic analyses by flow cytometry showed that 55% of Japanese CLL patients had a Matutes score of 4 or higher, which is lower than the rate of about 90% in Europeans. Mutated IGHV was identified in 80% of Japanese CLL patients, which is a higher rate than in Western patients. The most frequent IGHV gene was VH3-30 (15%), followed by VH3-23 (12%) and VH4-34 (10%). VH1-69, the most common gene in Western countries, was identified in only one patient. These results indicate that the pattern of immunophenotypes and IGHV gene usage in Japanese CLL patients differs from that in Western patients.

Human T-cell leukemia virus type I (HTLV-1) proviral load and disease progression in asymptomatic HTLV-1 carriers: a nationwide prospective study in Japan.

Definitive risk factors for the development of adult T-cell leukemia (ATL) among asymptomatic human T-cell leukemia virus type I (HTLV-1) carriers remain unclear. Recently, HTLV-1 proviral loads have been evaluated as important predictors of ATL, but a few small prospective studies have been conducted. We prospectively evaluated 1218 asymptomatic HTLV-1 carriers (426 males and 792 females) who were enrolled during 2002 to 2008. The proviral load at enrollment was significantly higher in males than females (median, 2.10 vs 1.39 copies/100 peripheral blood mononuclear cells [PBMCs]; P < .001), in those 40 to 49 and 50 to 59 years of age than that of those 40 years of age and younger (P = .02 and .007, respectively), and in those with a family history of ATL than those without the history (median, 2.32 vs 1.33 copies/100 PBMCs; P = .005). During follow-up, 14 participants progressed to overt ATL. Their baseline proviral load was high (range, 4.17-28.58 copies/100 PBMCs). None developed ATL among those with a baseline proviral load lower than approximately 4 copies. Multivariate Cox analyses indicated that not only a higher proviral load, advanced age, family history of ATL, and first opportunity for HTLV-1 testing during treatment for other diseases were independent risk factors for progression of ATL.

Successful treatment with tirabrutinib for relapsed lymphoplasmacytic lymphoma complicated by Bing-Neel syndrome.

A 53-year-old woman was diagnosed with lymphoplasmacytic lymphoma (LPL)/Waldenström's macroglobulinemia (WM) in 2008. Six courses of R-COP (rituximab, cyclophosphamide, vincristine, and prednisolone) resulted in complete remission, but LPL/WM relapsed in 2015. After six courses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone), the M-peak disappeared, but the patient presented with muscle weakness and sensory disturbance in the lower extremities. No lesions were apparent in the brain parenchyma, but T2-weighted magnetic resonance imaging (MRI) showed a signal-hyperintense area with contrast enhancement in the spinal cord at the C2-4 and Th2-3 levels, and cerebrospinal fluid (CSF) examination showed only a few mononuclear cells. In 2020, the patient started to require walking assistance, and MRI findings worsened. Neurologically, lower limb muscle strength was reduced (manual muscle test score 3), and sensations of touch and pain were about 30% of normal. Vibratory sensation was absent at the knees and medial malleoli, accompanied by dysuria due to neurogenic bladder. CSF cell count was 15/µl (all mononuclear cells). Bing-Neel syndrome (BNS) was diagnosed and tirabrutinib was started. Within 2 months of treatment, lower extremity muscle strength had normalized and MRI findings had improved. Tirabrutinib may offer a promising therapeutic option for BNS.

Fungal biomarker monitoring and CT scans for early detection of invasive fungal disease in neutropenic hematological patients.

OBJECTIVES: By using data from the CEDMIC trial (n = 413), we conducted a post-hoc analysis of the diagnostic value of biomarker monitoring and chest computed tomography (CT) scans for the early detection of invasive fungal disease (IFD) in neutropenic hematological patients. METHODS: IFDs were defined in accordance with the EORTC/MSG definition with some modifications. Biomarkers such as Aspergillus galactomannan (GM) and (1→3)-ß-D-glucan (ßDG) were measured weekly. RESULTS: The positive predictive value (PPV) of GM and ßDG in cases of high-risk treatment were 0.70 and 0.69, while those in low-risk treatment were 0.08 and 0, respectively. All of the positive biomarkers that were measured before the development of fever in low-risk treatment were false positives. The proportion of patients who had abnormal chest CT findings was 19% in persistent fever at 4-6 days, 57% at 7 days or later and 36% in recurrent fever. Sixty-nine percent of the patients who had abnormal findings at 7 days or later did not have abnormalities at 4-6 days. CONCLUSIONS: Afebrile screening of biomarkers in low-risk treatment is not useful. Chest CT should be reevaluated in persistent fever lasting for 7 days or longer even in patients who did not have abnormalities within 6 days.

Successful treatment with tirabrutinib for relapsed Bing-Neel syndrome following high-dose methotrexate and craniospinal irradiation.

A 63-year-old man was diagnosed with Waldenström's macroglobulinemia (WM). Six courses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) resulted in complete remission, but WM relapsed three years after R-CHOP. After six courses of BR (bendamustine, rituximab), the serum IgM level and CRP normalized. Four years after BR, the patient presented with muscle weakness, sensory disturbance, and myoclonus of lower limbs. T2-weighted magnetic resonance imaging (MRI) showed areas of signal hyperintensity with contrast enhancement in the right temporal and parietal lobes in brain parenchyma, medulla, bilateral basal ganglia, white matter of occipital lobe, and thoracic spinal cord at the Th2-11 levels. Open brain biopsy revealed diffuse proliferation of small lymphocytes and plasmacytoid lymphocytes on the brain surface and around cerebral blood vessels, resulting in a diagnosis of Bing-Neel syndrome (BNS). Two courses of R-MPV (rituximab, methotrexate, procarbazine, and vincristine) resulted in progressive disease, but the neurological symptoms and MRI findings improved following craniospinal irradiation of 30.6 Gy. Three years after craniospinal irradiation, T2-weighted MRI showed recurrence of BNS with progression of myoclonus of lower limbs and IgM elevation. Tirabrutinib was started for the second recurrence of WM and progression of BNS. Two months after the initiation of treatment with tirabrutinib, the myoclonus of lower limbs disappeared and the MRI findings showed improvement. Serum IgM levels decreased and no adverse events were observed. Tirabrutinib shows promise as a therapeutic option for relapsed BNS.

High incidence of cytomegalovirus, human herpesvirus-6, and Epstein-Barr virus reactivation in patients receiving cytotoxic chemotherapy for adult T cell leukemia.

The etiology of cytomegalovirus (CMV), human herpesvirus-6 (HHV-6), and Epstein-Barr virus (EBV) reactivation and the potential for complications following cytotoxic chemotherapy in the absence of allogeneic transplantation are not clearly understood. Patients with adult T cell leukemia (ATL) are susceptible to opportunistic infections. In this study, the incidence, kinetics and clinical significance of reactivation of CMV, HHV-6, and EBV in ATL patients were investigated. Viral DNA in a total of 468 plasma samples from 34 patients was quantified using real-time PCR. The probability of CMV, HHV-6, and EBV reactivation by 100 days after the start of chemotherapy was 50.6%, 52.3%, and 21.6%, respectively. Although most CMV reactivations were self-limited, plasma CMV DNA tended to persist or increase if the CMV DNA levels in plasma reached ≥ 10(4) copies/ml. CMV reactivation was negatively associated with survival, but the P-value for this association was near the borderline of statistical significance (P=0.052). One patient developed fatal interstitial pneumonia concomitant with peak CMV DNA accumulation (1.6 × 10(6) copies/ml plasma). Most HHV-6 and EBV reactivations were self-limited, and no disease resulting from HHV-6 or EBV was confirmed. HHV-6 and EBV reactivation were not associated with reduced survival (P=0.35 and 0.11, respectively). These findings demonstrated that subclinical reactivation of CMV, HHV-6, and EBV were common in ATL patients receiving chemotherapy. There were differences in the viral reactivation patterns among the three viruses. A CMV load ≥ 10(4) copies/ml plasma was indicative of subsequent exacerbation of CMV reactivation and developing serious clinical course.

Central nervous system involvement in intravascular large B-cell lymphoma: a retrospective analysis of 109 patients.

Intravascular large B-cell lymphoma (IVLBCL) is a rare disease entity with a high incidence of central nervous system (CNS) involvement at diagnosis. To evaluate CNS involvement, particularly recurrence including progression on therapy and relapse of IVLBCL, we retrospectively analyzed 109 patients with IVLBCL receiving chemotherapies with or without rituximab. In 82 patients (75%) without CNS involvement at initial diagnosis, risk of CNS recurrence at 3 years was 25% with a median follow-up in survivors of 39 months (range, 2-158 months). In 27 patients (25%) with CNS involvement at initial diagnosis, risk of CNS recurrence at 1 year was 25% with a median follow-up in survivors of 18 months (range, 10-77 months). Duration from diagnosis to CNS recurrence tended to be short in patients with CNS involvement at diagnosis. No significant difference in risk of CNS recurrence was found between patients receiving chemotherapies with or without rituximab. On multivariate analysis skin involvement at initial diagnosis was identified as a predictive factor for CNS recurrence in patients without CNS involvement at diagnosis (hazard ratio, 5.27; 95% confidence interval, 1.59-17.4; P = 0.007). Survival rate after CNS recurrence at 2 years was 12% in patients without CNS involvement at diagnosis. Central nervous system recurrence is a serious complication in IVLBCL patients and optimal strategies for CNS involvement should be established to obtain further improvements to clinical outcomes in the rituximab era.

[Retrospective analysis of thalidomide therapy in patients with relapsed/refractory multiple myeloma].

Thalidomide is now recognized as an important agent for multiple myeloma. In this study, we retrospectively analyzed the effect of thalidomide therapy in 52 patients with relapsed/refractory multiple myeloma. Median age was 70 years. Eight patients were treated with thalidomide alone, 36 with dexamethasone, and 8 with chemotherapy. The maintenance dose of thalidomide was 100 mg/day in 42 cases. The probability of overall survival and progression-free survival one year after the start of thalidomide were 76.2% and 70.9%, respectively. Complete or partial response was obtained in 16 patients (31%). The probability of survival was better in patients who obtained a partial or complete response than in non-responders (P=0.04). Adverse effects (CTCAE criteria Grade 3-4) were somnolence (n=3), constipation (n=5), peripheral neuropathy (n=1), deep vein thrombosis (n=1), anemia (n=10), leukocytopenia (n=10), and thrombocytopenia (n=3). The high incidence of cytopenia in this study suggests that the Japanese population tends to display bone marrow suppression after thalidomide therapy. Some patients developed peripheral neuropathy at the early stage of administration and attention was necessary. In conclusion, thalidomide therapy is safe and effective in patients with refractory multiple myeloma.

[Therapeutic choice for the chronic myeloid leukemia patients in chronic phase showing late suboptimal response to imatinib].

The response criteria proposed by European Leukemia Net are useful to predict the prognosis of de novo chronic myeloid leukemia (CML) patients in the chronic phase (CP) treated with imatinib. However, the clinical significance of late suboptimal response, which is defined as the achievement of CCgR without MMR after 18 months, is controversial. In this study, we retrospectively analyzed the clinical courses of 16 CML-CP patients, who satisfied the criteria for late suboptimal response. The median duration of imatinib treatment was 62 (25∼87) months. The median starting dose of imatinib was 400 mg/day. Imatinib dose was escalated to 600∼800 mg/day in 10 patients for various reasons. Among 4 patients who continued high-dose imatinib for late suboptimal response, 2 patients subsequently achieved MMR, and BCR-ABL mRNA transcript levels were decreasing in 2 patients. However, imatinib was kept at 300 or 400 mg/day in 6 patients. Among these six patients, 4 patients achieved MMR, while 2 failed to achieve MMR. None of 16 patients progressed to the acute phase or blast phase. Imatinib dose escalation was effective for late suboptimal response. Furthermore, a second tyrosine kinase inhibitor such as nilotinib may be more potent to reduce the risk of disease progression by achieving earlier MMR.

D-Index-Guided Early Antifungal Therapy Versus Empiric Antifungal Therapy for Persistent Febrile Neutropenia: A Randomized Controlled Noninferiority Trial.

PURPOSE: Empiric antifungal therapy (EAT) is recommended for persistent febrile neutropenia (FN), but in most patients, it is associated with overtreatment. The D-index, calculated as the area surrounded by the neutrophil curve and the horizontal line at a neutrophil count of 500/µL, reflects both the duration and depth of neutropenia and enables real-time monitoring of the risk of invasive fungal infection in individual patients at no cost. We investigated a novel approach for patients with persistent FN called D-index-guided early antifungal therapy (DET), in which antifungal treatment is postponed until a D-index reaches 5,500 or the detection of positive serum or imaging tests, and compared it with EAT in this multicenter open-label noninferiority randomized controlled trial. PATIENTS AND METHODS: We randomly assigned 423 patients who underwent chemotherapy or hematopoietic stem-cell transplantation for hematologic malignancies to the EAT or DET group. The prophylactic use of antifungal agents other than polyenes, echinocandins, or voriconazole was allowed. Micafungin at 150 mg per day was administered as EAT or DET. RESULTS: In an intent-to-treat analysis of 413 patients, the incidence of probable/proven invasive fungal infection was 2.5% in the EAT group and 0.5% in the DET group, which fulfilled the predetermined criterion of noninferiority of the DET group (-2.0%; 90% CI, -4.0% to 0.1%). The survival rate was 98.0% versus 98.6% at day 42 and 96.4% versus 96.2% at day 84. The use of micafungin was significantly reduced in the DET group (60.2% v 32.5%; P < .001). CONCLUSION: A novel strategy, DET, decreased the use and cost of antifungal agents without increasing invasive fungal infections and can be a reasonable alternative to empiric or preemptive antifungal therapy.

Efficacy and safety of micafungin in empiric and D-index-guided early antifungal therapy for febrile neutropenia; A subgroup analysis of the CEDMIC trial.

OBJECTIVES: The D-index is defined as the area over the neutrophil curve during neutropenia. The CEDMIC trial confirmed the noninferiority of D-index-guided early antifungal therapy (DET) using micafungin to empirical antifungal therapy (EAT). In this study, we evaluated the efficacy and safety of micafungin in these settings. METHODS: From the CEDMIC trial, we extracted 67 and 113 patients who received micafungin in the DET and EAT groups, respectively. Treatment success was defined as the fulfilment of all components of a five-part composite end point. Fever resolution was evaluated at seven days after the completion of therapy. RESULTS: The proportion of high-risk treatments including induction chemotherapy for acute leukemia and allogeneic hematopoietic stem cell transplantation was significantly higher in the DET group than in the EAT group (82.1% vs. 52.2%). The efficacy of micafungin was 68.7% (95%CI: 56.2-79.4) and 79.6% (71.0-86.6) in the DET and EAT groups, respectively. When we focused on high-risk treatments, the efficacy was 69.1% (55.2-80.9%) and 78.0% (65.3-87.7%), respectively (P = 0.30). There was no significant difference in any of the 5 components between the two groups. CONCLUSIONS: The efficacy of micafungin in patients undergoing high-risk treatment was not strongly impaired in DET compared to that in EAT.

Allogeneic hematopoietic stem cell transplantation using reduced-intensity conditioning for adult T cell leukemia/lymphoma: impact of antithymocyte globulin on clinical outcome.

Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective treatment for adult T cell leukemia/lymphoma (ATLL), but shows high mortality. We evaluated the feasibility of reduced-intensity transplantation using fludarabine and busulfan, with particular focus on the clinical impact of antithymocyte globulin (ATG) in the conditioning regimen. Fourteen elderly patients with aggressive ATLL were enrolled in the current study without ATG, and were compared to those in 15 patients who were treated similarly, but with ATG, in our previous study. Engraftment was prompt, and treatment was tolerable. Overall (OS) and progression-free survival (PFS) at 3 years were 36% and 31%, respectively. HTVL-1 proviral load became undetectable by the polymerase chain reaction in 62% of patients. Compared to the previous study with ATG, complete donor chimera was significantly delayed. Although early relapse tended to be decreased, OS or PFS was not improved significantly. Analysis of combined data from both our current and previous studies disclosed that grade I-II acute GVHD was the only factor that favorably affected OS and PFS. These data suggested the presence of a graft-versus-ATLL effect and the feasibility of a transplant procedure without ATG in elderly ATLL patients, but could not demonstrate the clinical benefit of incorporating ATG.

Deeper molecular response is a predictive factor for treatment-free remission after imatinib discontinuation in patients with chronic phase chronic myeloid leukemia: the JALSG-STIM213 study.

The objective of this prospective clinical trial (JALSG-STIM213, UMIN000011971) was to evaluate treatment-free remission (TFR) rates after discontinuation of imatinib in chronic myeloid leukemia (CML). CML patients who received imatinib treatment for at least 3 years and sustained deep molecular response for at least 2 years were eligible. Molecular recurrence was defined as loss of major molecular response (MMR). Of the 68 eligible patients, 38.2% were women, the median age was 55.0 years, and the median duration of imatinib treatment was 97.5 months. The 12-month TFR rate was 67.6%. Patients who lost MMR were immediately treated with imatinib again; all re-achieved MMR. Three-year treatment-free survival (TFS) was estimated as 64.6% using the Kaplan-Meier method. Undetectable molecular residual disease (UMRD) was defined as no BCR-ABL1 in > 100,000 ABL1 control genes using international scale polymerase chain reaction. UMRD at the study baseline was found to be predictive of continuation of TFR. Our findings suggest that CML patients who meet all the eligibility criteria that have commonly been used in the TFR trials are able to discontinue imatinib use safely. TFR may thus be valuable as a new goal for CML treatment in Japan.

Two Elderly Patients with Philadelphia Chromosome Positive Mixed Phenotype Acute Leukemia Who Were Successfully Treated with Dasatinib and Prednisolone.

Philadelphia chromosome positive (Ph+) mixed phenotype acute leukemia (MPAL) is a rare type of acute leukemia having both myeloid and lymphoid features for which no optimal treatment has yet been established. We herein describe two elderly Ph+MPAL patients who achieved molecular remission without any serious adverse events by treatment with dasatinib and prednisolone. Although dasatinib induction therapy combined with prednisolone is known to be a highly effective treatment for Ph+ acute lymphoblastic leukemia, its efficacy for Ph+MPAL has not been shown. The clinical courses of the present cases suggest that combination therapy with dasatinib and prednisolone is a safe and effective therapeutic modality in elderly Ph+MPAL patients.