ABSTRACT
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.
Subject(s)
Immunophenotyping , Leukemia, Lymphocytic, Chronic, B-Cell , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/epidemiology , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Humans , Japan/epidemiology , Aged , Male , Female , Middle Aged , Aged, 80 and over , Prospective Studies , Adult , Mutation , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Variable Region/geneticsABSTRACT
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.
Subject(s)
Craniospinal Irradiation , Myoclonus , Waldenstrom Macroglobulinemia , Humans , Male , Middle Aged , Bendamustine Hydrochloride , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Imidazoles , Immunoglobulin M/therapeutic use , Methotrexate/adverse effects , Myoclonus/drug therapy , Prednisolone/therapeutic use , Procarbazine , Pyrimidines , Rituximab/therapeutic use , Vincristine/therapeutic use , Waldenstrom Macroglobulinemia/pathologyABSTRACT
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 (1â3)-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.
Subject(s)
Invasive Fungal Infections , beta-Glucans , Biomarkers , Humans , Invasive Fungal Infections/diagnostic imaging , Mannans , Sensitivity and Specificity , Tomography, X-Ray ComputedABSTRACT
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.
Subject(s)
Lymphoma , Waldenstrom Macroglobulinemia , Female , Humans , Imidazoles/therapeutic use , Lymphoma/complications , Middle Aged , Pyrimidines/therapeutic use , Rituximab/therapeutic use , Waldenstrom Macroglobulinemia/complications , Waldenstrom Macroglobulinemia/drug therapy , Waldenstrom Macroglobulinemia/pathologyABSTRACT
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.
Subject(s)
Antifungal Agents/therapeutic use , Febrile Neutropenia/drug therapy , Micafungin/therapeutic use , Neutrophils/drug effects , Adult , Aged , Antifungal Agents/adverse effects , Febrile Neutropenia/immunology , Female , Humans , Male , Micafungin/adverse effects , Middle Aged , Neutrophils/chemistry , Treatment Outcome , Young AdultABSTRACT
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.
Subject(s)
Antifungal Agents/administration & dosage , Febrile Neutropenia/drug therapy , Febrile Neutropenia/microbiology , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/methods , Mycoses/prevention & control , Adult , Aged , Febrile Neutropenia/blood , Female , Fluconazole/administration & dosage , Hematologic Neoplasms/blood , Hematologic Neoplasms/drug therapy , Hematologic Neoplasms/microbiology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Itraconazole/administration & dosage , Leukocyte Count , Male , Micafungin/administration & dosage , Middle Aged , Mycoses/blood , Mycoses/etiology , Neutrophils/pathology , Young AdultSubject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Hematopoietic Stem Cell Transplantation , Leukemia-Lymphoma, Adult T-Cell , Adult , Aged , Aged, 80 and over , Allografts , Disease-Free Survival , Female , Follow-Up Studies , Humans , Leukemia-Lymphoma, Adult T-Cell/mortality , Leukemia-Lymphoma, Adult T-Cell/pathology , Leukemia-Lymphoma, Adult T-Cell/therapy , Male , Middle Aged , Survival RateABSTRACT
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.
Subject(s)
Imatinib Mesylate/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myeloid, Chronic-Phase/drug therapy , Leukemia, Myeloid, Chronic-Phase/genetics , Disease-Free Survival , Female , Fusion Proteins, bcr-abl/genetics , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/mortality , Leukemia, Myeloid, Chronic-Phase/mortality , Male , Middle Aged , Prospective Studies , Remission Induction , Treatment OutcomeSubject(s)
Anemia, Aplastic/therapy , Bone Marrow Transplantation , Influenza Vaccines/adverse effects , Lymphohistiocytosis, Hemophagocytic/etiology , Adult , Allografts , Chronic Disease , Graft vs Host Disease/drug therapy , Humans , Immunosuppressive Agents/administration & dosage , Infusions, Intravenous , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/drug therapy , Male , Methylprednisolone/administration & dosage , Prednisolone/administration & dosage , Tacrolimus/administration & dosage , Treatment OutcomeABSTRACT
Toxoplasmic encephalitis is a rare infectious complication in patients with hematological malignancy except for allogeneic hematopoietic stem cell transplantation (HSCT). We herein report a case of possible toxoplasmic encephalitis with untreated hairy cell leukemia variant. Magnetic resonance imaging showed multiple nodules with surrounding edema in the entire cerebrum. A polymerase chain reaction analysis for Toxoplasma gondii was negative. Her signs and symptoms fully recovered by empirical therapy with sulfadiazine and pyrimethamine. Toxoplasmic encephalitis may occur in patients who undergo non-allogeneic HSCT for hematological malignancies, even in those who have not been treated.
Subject(s)
Infectious Encephalitis/diagnosis , Leukemia, Hairy Cell/diagnosis , Toxoplasmosis, Cerebral/diagnosis , Aged , Animals , Antiprotozoal Agents/therapeutic use , Diagnosis, Differential , Drug Therapy, Combination , Female , Hemiplegia/etiology , Humans , Infectious Encephalitis/complications , Infectious Encephalitis/diagnostic imaging , Infectious Encephalitis/drug therapy , Leukemia, Hairy Cell/complications , Leukemia, Hairy Cell/diagnostic imaging , Leukemia, Hairy Cell/drug therapy , Magnetic Resonance Imaging , Pyrimethamine/therapeutic use , Sulfadiazine/therapeutic use , Toxoplasma/isolation & purification , Toxoplasmosis, Cerebral/complications , Toxoplasmosis, Cerebral/diagnostic imaging , Toxoplasmosis, Cerebral/drug therapyABSTRACT
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.
Subject(s)
Dasatinib/therapeutic use , Philadelphia Chromosome , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Prednisolone/therapeutic use , Acute Disease , Aged , Dasatinib/administration & dosage , Drug Therapy, Combination , Female , Humans , Phenotype , Prednisolone/administration & dosage , Treatment OutcomeSubject(s)
Amyloidosis/complications , Amyloidosis/diagnostic imaging , Lung Diseases/complications , Lung Diseases/diagnostic imaging , Multiple Myeloma/complications , Pulmonary Alveoli/diagnostic imaging , Diagnosis, Differential , Female , Humans , Lung/diagnostic imaging , Middle Aged , Tomography, X-Ray ComputedSubject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Epstein-Barr Virus Infections , Herpesvirus 4, Human , Lymphoma, Large B-Cell, Diffuse , Muscle Neoplasms , Psoas Muscles , Aged , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Epstein-Barr Virus Infections/diagnostic imaging , Epstein-Barr Virus Infections/drug therapy , Epstein-Barr Virus Infections/metabolism , Etoposide/administration & dosage , Humans , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/metabolism , Lymphoma, Large B-Cell, Diffuse/virology , Male , Muscle Neoplasms/diagnostic imaging , Muscle Neoplasms/drug therapy , Muscle Neoplasms/metabolism , Muscle Neoplasms/virology , Prednisone/administration & dosage , Psoas Muscles/diagnostic imaging , Psoas Muscles/metabolism , Radiography , Rituximab , Vincristine/administration & dosageABSTRACT
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.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Transplantation/statistics & numerical data , Leukemia-Lymphoma, Adult T-Cell/therapy , Aged , Allografts , Antineoplastic Agents/therapeutic use , Combined Modality Therapy , Disease Management , Disease-Free Survival , Female , Humans , Infections/mortality , Japan/epidemiology , Kaplan-Meier Estimate , Leukemia-Lymphoma, Adult T-Cell/classification , Leukemia-Lymphoma, Adult T-Cell/drug therapy , Leukemia-Lymphoma, Adult T-Cell/etiology , Leukemia-Lymphoma, Adult T-Cell/mortality , Male , Middle Aged , Mortality/trends , Prognosis , Retrospective Studies , Treatment OutcomeABSTRACT
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.
Subject(s)
Hemophilia A/chemically induced , Multiple Myeloma/drug therapy , Thalidomide/analogs & derivatives , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Disease Progression , Female , Humans , Lenalidomide , Multiple Myeloma/pathology , Thalidomide/adverse effects , Thalidomide/therapeutic useABSTRACT
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.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia-Lymphoma, Adult T-Cell/drug therapy , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/adverse effects , Carboplatin/therapeutic use , Cyclophosphamide/adverse effects , Cyclophosphamide/therapeutic use , Disease Progression , Doxorubicin/adverse effects , Doxorubicin/therapeutic use , Etoposide/adverse effects , Etoposide/therapeutic use , Female , Humans , Leukemia-Lymphoma, Adult T-Cell/mortality , Leukemia-Lymphoma, Adult T-Cell/pathology , Male , Middle Aged , Nitrosourea Compounds/adverse effects , Nitrosourea Compounds/therapeutic use , Prednisolone/adverse effects , Prednisolone/therapeutic use , Treatment Outcome , Vincristine/adverse effects , Vincristine/therapeutic use , Vindesine/adverse effects , Vindesine/therapeutic useABSTRACT
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.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Extranodal NK-T-Cell/drug therapy , Adult , Asparaginase/administration & dosage , Cytarabine/administration & dosage , Dexamethasone/administration & dosage , Drug Administration Schedule , Drug Resistance, Neoplasm , Etoposide/administration & dosage , Humans , Ifosfamide/administration & dosage , Male , Methotrexate/administration & dosage , Treatment OutcomeABSTRACT
PURPOSE: The prognosis of acute- and lymphoma-type adult T-cell leukemia/lymphoma (ATL) is poor, but there is marked diversity in survival outcomes. The aim of this study was to develop a prognostic index (PI) for acute- and lymphoma-type ATL (ATL-PI). PATIENTS AND METHODS: In a retrospective review, data from 807 patients newly diagnosed with acute- and lymphoma-type ATL between January 2000 and May 2009 were evaluated. We randomly divided subjects into training (n = 404) and validation (n = 403) samples, and developed a PI using a multivariable fractional polynomial model. RESULTS: Median overall survival time (MST) for the 807 patients was 7.7 months. The Ann Arbor stage (I and II v III and IV), performance status (0 to 1 v 2 to 4), and three continuous variables (age, serum albumin, and soluble interleukin-2 receptor [sIL-2R]) were identified as independent prognostic factors in the training sample. Using these variables, a prognostic model was devised to identify different levels of risk. In the validation sample, MSTs were 3.6, 7.3, and 16.2 months for patients at high, intermediate, and low risk, respectively (P < .001; χ(2) = 89.7, 2 df; log-rank test). We also simplified the original ATL-PI according to dichotomizing age at 70 years, serum albumin at 3.5 g/dL, and sIL-2R at 20,000 U/mL and developed an easily calculable PI with prognostic discrimination power (P < .001; χ(2) = 74.2, 2 df; log-rank test). CONCLUSION: The ATL-PI is a promising new tool for identifying patients with acute- and lymphoma-type ATL at different risks.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Leukemia-Lymphoma, Adult T-Cell/mortality , Leukemia-Lymphoma, Adult T-Cell/pathology , Receptors, Interleukin-2/blood , Age Factors , Aged , Aged, 80 and over , Albumins/metabolism , Biomarkers, Tumor/blood , Cause of Death , Cohort Studies , Disease-Free Survival , Female , Humans , Japan , Kaplan-Meier Estimate , Leukemia-Lymphoma, Adult T-Cell/drug therapy , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Prognosis , Proportional Hazards Models , Reproducibility of Results , Retrospective Studies , Risk Assessment , Sex Factors , Statistics, Nonparametric , Survival AnalysisABSTRACT
PURPOSE: Adult T-cell leukemia-lymphoma (ATL) is usually resistant to conventional chemotherapies, and there are few other treatment options. Because CC chemokine receptor 4 (CCR4) is expressed on tumor cells from most patients with ATL, KW-0761, a humanized anti-CCR4 monoclonal antibody, which markedly enhances antibody-dependent cellular cytotoxicity, was evaluated in the treatment of patients with relapsed ATL. PATIENTS AND METHODS: A multicenter phase II study of KW-0761 for patients with relapsed, aggressive CCR4-positive ATL was conducted to evaluate efficacy, pharmacokinetic profile, and safety. The primary end point was overall response rate, and secondary end points included progression-free and overall survival from the first dose of KW-0761. Patients received intravenous infusions of KW-0761 once per week for 8 weeks at a dose of 1.0 mg/kg. RESULTS: Of 28 patients enrolled onto the study, 27 received at least one infusion of KW-0761. Objective responses were noted in 13 of 26 evaluable patients, including eight complete responses, with an overall response rate of 50% (95% CI, 30% to 70%). Median progression-free and overall survival were 5.2 and 13.7 months, respectively. The mean half-life period after the eighth infusion was 422 ± 147 hours (± standard deviation). The most common adverse events were infusion reactions (89%) and skin rashes (63%), which were manageable and reversible in all cases. CONCLUSION: KW-0761 demonstrated clinically meaningful antitumor activity in patients with relapsed ATL, with an acceptable toxicity profile. Further investigation of KW-0761 for treatment of ATL and other T-cell neoplasms is warranted.