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1.
Cancer Sci ; 2024 May 16.
Article in English | MEDLINE | ID: mdl-38757410

ABSTRACT

The anti-CD38 antibody daratumumab (Dara) has been reported to improve the prognosis of multiple myeloma (MM) patients, but its use before autologous stem cell transplantation (ASCT) remains controversial. To clarify the prognostic impact of Dara before ASCT on MM, we performed a retrospective observational analysis. We analyzed 2626 patients who underwent ASCT between 2017 and 2020. In the comparison between patients not administered Dara (Dara- group) and those administered Dara (Dara+ group), the 1-year progression-free survival (PFS) rates were 87.4% and 77.3% and the 1-year overall survival (OS) rates were 96.7% and 90.0%, respectively. In multivariate analysis, age <65 years (p = 0.015), low international staging system (ISS) stage (p < 0.001), absence of unfavorable cytogenic abnormalities (p < 0.001), no Dara use before ASCT (p = 0.037), and good treatment response before ASCT (p < 0.001) were independently associated with superior PFS. In matched pair analysis, the PFS/OS of the Dara- group were also significantly superior. For MM patients who achieved complete or very good partial response (CR/VGPR) by Dara addition before ASCT, both PFS and OS significantly improved. However, in patients who did not achieve CR/VGPR before ASCT, the PFS/OS of the Dara+ group were significantly inferior to those of the Dara- group.

2.
Int J Hematol ; 119(1): 39-49, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38103160

ABSTRACT

Post-transplantation therapy is commonly performed in patients with myeloma and can prolong progression-free survival (PFS). However, whether post-transplantation therapy contributes to achieving and continuing MRD-negativity remains controversial. This retrospective analysis aimed to evaluate the clinical impact of post-transplantation therapy, including tandem autologous stem cell transplantation (ASCT), in myeloma patients. The subjects were 79 patients (median age: 62 years) who received induction therapy, including bortezomib and/or lenalidomide, of whom 58 underwent post-transplantation therapy. At the median follow-up time of 50 months, the 4-year PFS rate was significantly higher in patients who underwent post-transplantation therapy than those who did not (60.6% vs. 28.6%, P = 0.012). Multivariate analysis revealed post-transplantation therapy to be a significant prognostic factor for long PFS. Tandem ASCT followed by consolidation and/or maintenance therapies improved PFS and OS. The minimal residual disease (MRD)-negative rate was significantly higher in patients who underwent post-transplantation therapy than those who did not (50.9% vs. 16.7%, P = 0.006). Post-transplantation therapy contributed to sustained MRD-negativity, which predicted long PFS and overall survival. Patients frequently discontinued post-transplantation therapy due to adverse events within 4 months. In conclusion, post-transplantation therapy improved PFS and contributed to sustained MRD-negativity in myeloma patients.


Subject(s)
Hematopoietic Stem Cell Transplantation , Multiple Myeloma , Humans , Middle Aged , Multiple Myeloma/drug therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Treatment Outcome , Retrospective Studies , Transplantation, Autologous , Neoplasm, Residual/drug therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects
3.
Transplant Cell Ther ; 29(11): 688.e1-688.e13, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37574125

ABSTRACT

Autologous stem cell transplantation (ASCT) is the standard of care for myeloma patients who achieve partial response (PR) or better after induction therapy. However, its clinical significance in patients with suboptimal response (SR) before ASCT, including stable disease (SD) and progressive disease (PD), has not been established. Additionally, functional high-risk, including SR and early PD within 12 months, was a poor prognostic factor up to now. This study aimed to evaluate the efficacy of ASCT in myeloma patients with SR in the novel agent era. This multicenter retrospective study was conducted using the Transplant Registry Unified Management Program database of the Japanese Society of Transplantation and Cellular Therapy and included 3898 transplantation-eligible patients with newly diagnosed multiple myeloma who underwent ASCT between 2007 and 2020 and were followed up until 2021. The SR rate was 4.7%, including 1.7% with PD. In survival time analysis for overall cases, a significant difference in PFS between the very good partial response (VGPR) and PR groups was observed, whereas there was no significant difference in overall survival (OS) between the VGPR and PR groups. Additionally, there was no significant difference in OS or PFS between the PR and SD groups. Therefore, we focused on the PR, SD, and PD groups, as the purpose of this retrospective study was to investigate the clinical significance of ASCT in patients with SR compared with those with PR. The median patient age was 60 years (range, 30 to 77 years). In total, 1605 (97.4%) patients received bortezomib, 561 (38.2%) received an immunomodulatory drug (ImiD), and 512 (34.9%) received both bortezomib and an ImiD. A total of 558 patients (38.0%) received reinduction therapy. There were 229 patients (37.7%) with high-risk cytogenetics (HRCA). With a median follow-up of 31.7 months, there was a significant difference in 30-month OS rates among the PR, SD, and PD groups (86.3%, 78.5%, and 39.4%, respectively; P <.001). OS was significantly shorter in the SD group compared to the PR group among the patients with HRCA (P < .001) and patients treated with reinduction therapy (P = .013). In the PD group, the 30-month OS and PFS rates were 39.4% and 17.9%, respectively. Finally, early PD within 12 months after ASCT was predictive of short OS, whereas OS without early PD even in the PD group was similar to that in the SD and PR groups. In conclusion, OS in the SR group was not always short, but SR in the HRCA and the reinduction therapy groups was predictive of short OS, so that therapeutic alternatives to ASCT are needed. OS in the PD group was significantly short, but ASCT improved clinical outcomes when early PD did not occur even in the PD group.


Subject(s)
Hematopoietic Stem Cell Transplantation , Multiple Myeloma , Humans , Adult , Middle Aged , Aged , Multiple Myeloma/drug therapy , Retrospective Studies , Bortezomib/therapeutic use , Treatment Outcome , Disease-Free Survival , Transplantation, Autologous
4.
Transplant Cell Ther ; 29(5): 332.e1-332.e11, 2023 05.
Article in English | MEDLINE | ID: mdl-36796517

ABSTRACT

The alkylating agent busulfan is commonly used as conditioning in allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia (AML). However, a consensus has not yet been reached regarding the optimal busulfan dose in cord blood transplantation (CBT). Therefore, we conducted this large nationwide cohort study to retrospectively analyze the outcomes of CBT in patients with AML receiving busulfan at intermediate (6.4 mg/kg i.v.; BU2) or higher (12.8 mg/kg i.v.; BU4) doses within a fludarabine/i.v. busulfan (FLU/BU) regimen. Among 475 patients who underwent their first CBT following FLU/BU conditioning between 2007 and 2018, 162 received BU2 and 313 received BU4. Multivariate analysis identified BU4 as a significant factor for longer disease-free survival (hazard ratio [HR], .85; 95% confidence interval [CI], .75 to .97; P = .014) and a lower relapse rate (HR, .84; 95% CI, .72 to .98; P = .030). No significant differences were observed in non-relapse mortality between BU4 and BU2 (HR, 1.05; 95% CI, .88-1.26; P = .57). Subgroup analyses showed that BU4 provided significant benefits for patients who underwent transplantation while not in complete remission (CR) and those age <60 years. Our present results suggest that higher busulfan doses are preferable in patients undergoing CBT, particularly those not in CR and younger patients.


Subject(s)
Cord Blood Stem Cell Transplantation , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Humans , Middle Aged , Busulfan/therapeutic use , Cohort Studies , Retrospective Studies , Hematopoietic Stem Cell Transplantation/methods , Leukemia, Myeloid, Acute/therapy , Recurrence
5.
Eur J Haematol ; 110(4): 444-454, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36597575

ABSTRACT

Tandem autologous stem cell transplantation (ASCT) has been reconsidered for high-risk patients with myeloma, and the eligibility criteria for up-front ASCT have been updated to include more elderly patients. This study aimed to evaluate the efficacy and tolerability of tandem ASCT in elderly patients with myeloma compared to tandem ASCT in young patients and single ASCT in elderly patients. A retrospective study using the Transplant Registry Unified Management Program database of the Japanese Society for Transplantation and Cellular Therapy, which included 64 elderly and 613 young patients who received tandem ASCT, and 891 elderly patients who received single ASCT, was conducted. The median overall survival (OS) over 38.5 months in the elderly and young patients who received tandem ASCT, and elderly patients who received single ASCT was 78.9, 92.5, and 77.1 months, respectively; no significant difference in the median OS was observed. The cumulative incidence of transplantation-related mortality was similar in the elderly and young patients receiving tandem ASCT. High-risk cytogenetic abnormality was not identified as a poor prognostic factor for OS in elderly patients who received tandem ASCT but in those who received single ASCT. Thus, tandem ASCT was effective and tolerable in elderly patients with myeloma.


Subject(s)
Hematopoietic Stem Cell Transplantation , Multiple Myeloma , Humans , Aged , Retrospective Studies , Transplantation, Autologous , Stem Cell Transplantation
6.
NPJ Syst Biol Appl ; 8(1): 39, 2022 10 13.
Article in English | MEDLINE | ID: mdl-36229495

ABSTRACT

Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by the BCR-ABL1 tyrosine kinase. Although ABL1-specific tyrosine kinase inhibitors (TKIs) including nilotinib have dramatically improved the prognosis of patients with CML, the TKI efficacy depends on the individual patient. In this work, we found that the patients with different nilotinib responses can be classified by using the estimated parameters of our simple dynamical model with two common laboratory findings. Furthermore, our proposed method identified patients who failed to achieve a treatment goal with high fidelity according to the data collected only at three initial time points during nilotinib therapy. Since our model relies on the general properties of TKI response, our framework would be applicable to CML patients who receive frontline nilotinib or other TKIs.


Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Protein Kinase Inhibitors , Fusion Proteins, bcr-abl/genetics , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/pharmacology , Pyrimidines/therapeutic use
7.
Lancet Haematol ; 8(12): e902-e911, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34826413

ABSTRACT

BACKGROUND: BCR-ABL1 tyrosine kinase inhibitors (TKIs) are commonly initiated in older patients with chronic myeloid leukaemia in the chronic phase at standard doses. However, because of their safety profile in this population, appropriate therapy has not been established. We aimed to investigate whether a lower than standard dose of dasatinib was an appropriate therapy for older patients with chronic myeloid leukaemia in the chronic phase. METHODS: DAsatinib, Very Low-dose, for Elderly CML-CP patients (DAVLEC) was a multicentre, single-arm, phase 2 trial done in 25 Japanese hospitals. We enrolled patients older than 70 years with newly diagnosed chronic myeloid leukaemia in the chronic phase, ECOG performance status 0-2, and no previous treatment for CML other than hydroxyurea within 4 weeks. Second-generation TKI dasatinib was given orally at a starting dose of 20% of the standard dose (20 mg/day). If the treatment was assessed as optimal response at 3 months, 6 months, and 9 months and adverse events were grade 2 or better (according to the NCI Common Toxicity Criteria v 4.0), the same dose was continued. If response was suboptimal and adverse events were grade 2 or better, the dose was increased by 20 mg/day. Once a dose reduction had been made because of a grade 3 or worse adverse event, there were no further dose increases. Treatment was discontinued if assessed as failure (disease progression to the accelerated phase or acute phase). The primary endpoint was the achievement of major molecular response at 12 months, assessed using a per-protocol analysis. This trial is registered at with the UMIN clinical trial registry, UMIN000024548, and has completed its planned observation period. FINDINGS: Between Nov 1, 2016, and Oct 30, 2019, 52 patients received first-line dasatinib therapy at 20 mg/day. The median age at diagnosis was 77·5 years (73·5-83·0). 35 (67%) patients were male and 17 (33%) were female. 31 (60%) of 52 patients reached major molecular response at 12 months (one-sided 95% CI 48-71), with a median follow-up of 366 days (IQR 353-372). Grade 3-4 adverse events were reported in 12 (23%) patients. Neutropenia was the most frequent grade 3-4 adverse event, occurring in three (6%) patients. No treatment-related deaths were observed. INTERPRETATION: Low-dose dasatinib at 20mg/day is worthy of consideration as a starting dose for older patients with newly diagnosed chronic myeloid leukaemia in the chronic phase. However, this dose needs to be further studied in a larger cohort and with a more ethnically diverse population. FUNDING: Bristol-Myers Squibb.


Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Aged , Dasatinib/adverse effects , Drug Administration Schedule , Female , Fusion Proteins, bcr-abl , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Male , Treatment Outcome
8.
Cancers (Basel) ; 13(19)2021 Sep 28.
Article in English | MEDLINE | ID: mdl-34638353

ABSTRACT

Improving the immunological environment and eradicating minimal residual disease (MRD) are the two main treatment goals for long-term survival in patients with multiple myeloma (MM). Immunomodulatory drugs (IMiDs), monoclonal antibody drugs (MoAbs), and autologous grafts for autologous stem cell transplantation (ASCT) can improve the immunological microenvironment. ASCT, MoAbs, and proteasome inhibitors (PIs) may be important for the achievement of MRD negativity. An improved immunological environment may be useful for maintaining MRD negativity, although the specific treatment for persistent MRD negativity is unknown. However, whether the ongoing treatment should be continued or changed if the MRD status remains positive is controversial. In this case, genetic, immunophenotypic, and clinical analysis of residual myeloma cells may be necessary to select the effective treatment for the residual myeloma cells. The purpose of this review is to discuss the MM treatment strategy to "cure MM" based on currently available therapies, including IMiDs, PIs, MoAbs, and ASCT, and expected immunotherapies, such as chimeric antigen receptor T cell (CAR-T) therapy, via improvement of the immunological environment and maintenance of MRD negativity.

10.
Int J Hematol ; 114(5): 599-607, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34339005

ABSTRACT

Minimal residual disease (MRD) is a surrogate marker for survival in multiple myeloma (MM), while the lymphocyte-to-monocyte ratio (LMR) is a prognostic factor associated with the patients' immunological status. We retrospectively evaluated the clinical impact of MRD negativity and LMR. MRD was analyzed by multicolor flowcytometry (threshold, 1 × 10-5). Fifty-eight patients (median age 70 years) who achieved complete response were included in this study. Twenty-two patients received autologous stem cell transplantation, 14 received daratumumab-based chemotherapy, and 22 received another treatment. Forty-one (70.7%) patients achieved MRD negativity. Over the median follow-up time of 15.1 months, PFS in MRD-negative patients was significantly longer than in MRD-positive patients (P = 0.020). In addition, a high LMR at MRD assessment was associated with MRD negativity (P = 0.019) and long PFS (P = 0.009). Finally, neither MRD negativity nor high LMR at MRD assessment was associated with significantly shorter PFS compared with MRD positivity or low LMR (P = 0.002). In conclusion, high LMR was associated with MRD negativity and can be used as a predictor of long PFS. Change of treatment strategy might be essential for patients with MRD positivity and high LMR at MRD assessment due to their short PFS.


Subject(s)
Leukocyte Count , Lymphocyte Count , Lymphocytes/pathology , Monocytes/pathology , Multiple Myeloma/blood , Multiple Myeloma/pathology , Aged , Aged, 80 and over , Biomarkers , Biomarkers, Tumor , Disease Management , Disease Susceptibility , Female , Humans , Male , Middle Aged , Multiple Myeloma/etiology , Multiple Myeloma/mortality , Neoplasm, Residual/pathology , Prognosis , Retrospective Studies
11.
JBJS Case Connect ; 11(3)2021 08 27.
Article in English | MEDLINE | ID: mdl-34449450

ABSTRACT

CASE: Acute compartment syndrome (ACS) with acquired hemophilia A (AHA) is rare and has no established treatment strategy. A 64-year-old woman presented with a giant hematoma in the rectus abdominis. Laboratory findings included decreased hemoglobin and increased activated partial thromboplastin time. Arterial embolization was performed for hemostasis. After catheter removal, she developed severe arm pain and numbness with blistering. Fasciotomy was performed to decrease intracompartmental pressure. Laboratory investigations revealed decreased factor VIII (FVIII) activity and increased FVIII inhibitor. AHA was diagnosed and treated with immunosuppressive and FVIII inhibitor-bypassing agents. CONCLUSIONS: Fasciotomy should be performed promptly if ACS with AHA is suspected.


Subject(s)
Compartment Syndromes , Hemophilia A , Compartment Syndromes/complications , Compartment Syndromes/surgery , Factor VIII , Female , Hemophilia A/complications , Humans , Middle Aged , Partial Thromboplastin Time , Upper Extremity
12.
Rinsho Ketsueki ; 62(1): 55-57, 2021.
Article in Japanese | MEDLINE | ID: mdl-33551427

ABSTRACT

A 68-year-old male presented with appetite loss and abdominal distention. The whole-body computed tomography scan revealed an ileocecal mass with a large amount of ascites, which was consistent with malignant lymphoma. Due to the worsening of his general condition following admission, he was intubated and admitted to the intensive care unit (ICU). In the ICU, we performed a core-needle biopsy (CNB) on the left peritoneal mass, the findings of which showed a pathological diffuse infiltration of CD20+ middle-sized lymphoid cells. After chemotherapy was initiated, the patient showed complete response, suggesting that CNB can be performed immediately and safely even on a critically ill patient.


Subject(s)
Lymphoma, B-Cell , Aged , Biopsy, Large-Core Needle , Humans , Intensive Care Units , Lymphoma, B-Cell/diagnosis , Lymphoma, B-Cell/drug therapy , Lymphoma, B-Cell/pathology , Male , Retrospective Studies
13.
Cancers (Basel) ; 13(2)2021 Jan 08.
Article in English | MEDLINE | ID: mdl-33435539

ABSTRACT

Multiple myeloma is an uncurable hematological malignancy because of obtained drug resistance. Microenvironment and clonal evolution induce myeloma cells to develop de novo and acquired drug resistance, respectively. Cell adhesion-mediated drug resistance, which is induced by the interaction between myeloma and bone marrow stromal cells, and soluble factor-mediated drug resistance, which is induced by cytokines and growth factors, are two types of de novo drug resistance. The microenvironment, including conditions such as hypoxia, vascular and endosteal niches, contributes toward de novo drug resistance. Clonal evolution was associated with acquired drug resistance and classified as branching, linear, and neutral evolutions. The branching evolution is dependent on the microenvironment and escape of immunological surveillance while the linear and neutral evolution is independent of the microenvironment and associated with aggressive recurrence and poor prognosis. Proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibody agents (MoAbs), and autologous stem cell transplantation (ASCT) have improved prognosis of myeloma via improvement of the microenvironment. The initial treatment plays the most important role considering de novo and acquired drug resistance and should contain PIs, IMIDs, MoAb and ASCT. This review summarizes the role of anti-myeloma agents for microenvironment and clonal evolution and treatment strategies to overcome drug resistance.

14.
J Infect Chemother ; 27(4): 639-641, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33214069

ABSTRACT

The FMS-related tyrosine kinase 3 (FLT3) internal tandem duplication mutations (FLT3-ITD) positive acute myeloid leukemia (AML) is a disease with a dismal outcome. Gilteritinib is a second-generation FLT3 inhibitor with activity against ITD and high affinity toward the FLT3 receptor, thereby showing therapeutic potential for relapsed/refractory FLT3-mutated AML. Bone marrow transplantation (BMT) from a human leukocyte antigen (HLA) identical sibling donor was performed in a 38-year-old Japanese male with FLT3-ITD positive AML. Neutrophil engraftment (>0.5 × 109/L) was achieved on day 16, and bone marrow remission was revealed on day 32. The patient's AML relapsed hematologically four months after BMT and was resistant to salvage chemotherapy. Gilteritinib was administered and the patient achieved non-remission but 'stable disease' status according to the response criteria. During administration, liver damage was observed but controllable. The patient received cord blood transplantation (CBT) as the second hematopoietic stem cell transplantation (HSCT) three months after relapse and achieved second remission. There was no evidence of recurrence of AML four months after CBT. This case demonstrates that gilteritinib can control FLT3-ITD positive AML that relapsed early after initial HSCT and can bridge to second HSCT.


Subject(s)
Cord Blood Stem Cell Transplantation , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Adult , Aniline Compounds , Bone Marrow Transplantation , Humans , Leukemia, Myeloid, Acute/drug therapy , Male , Mutation , Pyrazines , fms-Like Tyrosine Kinase 3/genetics
15.
World Neurosurg ; 143: 247-260, 2020 11.
Article in English | MEDLINE | ID: mdl-32768593

ABSTRACT

BACKGROUND: We have reported an extremely rare case of a frontal convexity tumor diagnosed as IgG4-related disease (IgG4-RD) with unique neuroradiological images. CASE DESCRIPTION: A 64-year-old man with a history of monoclonal gammopathy of undetermined significance and conservative treatment had presented with a left facial spasm. Computed tomography showed a high-density round tumor with perifocal edema in the right frontal convexity. Magnetic resonance imaging demonstrated unique findings, including low signal intensity on T1- and T2-weighted, fluid-attenuated inversion recovery, and diffusion-weighted images, with slight gadolinium enhancement. The tumor was totally removed via right frontal craniotomy. It had been located in the subdural space, was not adherent to the dura, and was less vascular than meningiomas. Histological investigation demonstrated plasma cells that were strongly positive for IgG4 and contained κ and λ light chains at a ratio of 1.5:1. The serum IgG4 level was elevated. The tumor met the diagnostic criteria for IgG4-RD. The patient was followed up for 3 years during postoperative adjuvant steroid therapy. The steroid therapy was discontinued, and during the next 4 years, neither tumor recurrence nor symptoms were observed. CONCLUSION: Intracranial IgG4-RD with smoldering monoclonal gammopathy of undetermined significance is extremely rare. We reviewed the differential diagnosis of plasma cell granuloma and plasmacytoma, therapeutic implications, and clinical outcomes. Complete resection of a conspicuous and solitary IgG4-RD lesion in the frontal convexity is simple and could provide a cure with less-aggressive adjuvant therapy.


Subject(s)
Immunoglobulin G4-Related Disease/complications , Immunoglobulin G4-Related Disease/immunology , Smoldering Multiple Myeloma/complications , Adolescent , Adult , Aged , Anti-Inflammatory Agents/therapeutic use , Child , Child, Preschool , Craniotomy , Diffusion Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neurosurgical Procedures , Paraproteinemias/complications , Smoldering Multiple Myeloma/immunology , Smoldering Multiple Myeloma/surgery , Steroids/therapeutic use , Tomography, X-Ray Computed , Treatment Outcome , Young Adult
16.
Cancer Sci ; 111(8): 2923-2934, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32614159

ABSTRACT

This study presents the final report of the multicenter, prospective tyrosine kinase inhibitor discontinuation study, D-STOP, after a 3-year follow-up of 54 patients with chronic CML who discontinued dasatinib after a sustained deep molecular response (DMR) for ≥2 years with dasatinib treatment. Estimated treatment-free remission (TFR) rates at 12 and 36 months were 63.0% [95% confidence interval (CI): 48.7-74.3] and 59.3% (95% CI: 45.0-71.0), respectively. CD3- CD56+ NK, CD16+ CD56+ NK, and CD57+ CD56+ NK large granular lymphocyte (NK-LGL), CD8+ CD4- cytotoxic T cell, and CD57+ CD3+ T-LGL cell numbers were relatively elevated throughout the 24-month consolidation only in failed patients who molecularly relapsed within 12 months. In successful patients, these subsets elevated transiently after 12 months, but returned to basal levels after 24-month consolidation. Therefore, smaller changes in NK/T, particularly the NK subset throughout consolidation, reflected higher TFR rates. TFR rates of those patients exhibiting elevation in CD3- CD56+ NK >376 cells/µL, CD16+ CD56+ NK > 241 cells/µL, or CD57+ CD56+ NK-LGL >242 cells/µL during consolidation compared with others were 26.7% (8.3%-49.6%) vs 78.3% (55.4%-90.3%), HR 0.032 (0.0027-0.38; P = .0064), 31.2% (11.4%-53.6%) vs 85.0% (60.4%-94.9%), HR 0.039 (0.0031-0.48; P = .011), or 36.8% (16.5%-57.5%) vs 77.3% (53.7%-89.8%), HR 0.21 (0.065-0.69; P = .010), respectively. Therefore, silent responses of T/NK subsets to dasatinib throughout consolidation were significant for longer TFR. Elevated NK/T, particularly NK lymphocytes responsive to dasatinib, may be immunologically insufficient to maintain TFR. Their decline, subsequently replaced by altered lymphocyte population with less response to dasatinib during sustained DMR, might be immunologically significant. (D-STOP, NCT01627132).


Subject(s)
Dasatinib/therapeutic use , Killer Cells, Natural , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Protein Kinase Inhibitors/therapeutic use , T-Lymphocytes, Cytotoxic , Adult , Aged , Aged, 80 and over , Dasatinib/pharmacology , Female , Follow-Up Studies , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood , Lymphocyte Count , Male , Middle Aged , Prospective Studies , Protein Kinase Inhibitors/pharmacology , Remission Induction/methods , Treatment Outcome
17.
Rinsho Shinkeigaku ; 60(7): 504-507, 2020 Jul 31.
Article in Japanese | MEDLINE | ID: mdl-32536666

ABSTRACT

This is the rare case report that bilateral vagus nerve paralysis was emerged as the initial symptom of acute myelogenous leukemia (AML). An 83-year-old man admitted to our hospital because of dysphagia. His dysphagia progressed two months prior to admission. Although physical examination revealed no abnormality, videoendoscopy and videofluorography examination clearly revealed bilateral vagus nerve palsy. Brain MRI showed hypointense signals at the bilateral clivus on T1 weighted images, suggesting tumor infiltration to bilateral petroclivus. He was diagnosed as AML by blood samples and bone marrow biopsy. After initiation of the treatment including radiation therapy, dysphagia shows mild improvement. Although bilateral cranial nerve palsy due to malignant tumor involving at the clivus is very uncommon, we should pay attention to the symptom.


Subject(s)
Cranial Nerve Diseases/etiology , Deglutition Disorders/etiology , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/diagnosis , Vagus Nerve , Aged, 80 and over , Brain/diagnostic imaging , Brain/pathology , Diagnosis, Differential , Diffusion Magnetic Resonance Imaging , Humans , Male
18.
Cancer Med ; 9(11): 3742-3751, 2020 06.
Article in English | MEDLINE | ID: mdl-32253827

ABSTRACT

For patients who have chronic myeloid leukemia (CML), one of the primary treatment options is administration of nilotinib 300 mg twice daily (BID). In previous studies which compared outcomes associated with nilotinib or imatinib treatment, nilotinib achieved a higher rate of deep molecular response (MR). We conducted a phase II, open-label, multicenter study to investigate an intrapatient nilotinib dose-escalation strategy for patients with newly diagnosed chronic-phase (CP) CML based on early MR4.5 achievement. The primary study endpoint was achievement of MR4.5 by 24 months following the initiation of nilotinib 300 mg BID. Fifty-three patients were enrolled, 51 received nilotinib, and 37 completed the treatment. An increase in the nilotinib dose (to 400 mg BID) was allowed when patients satisfied our criteria for no optimal response at any time point. The median (range) dose intensity was 600 (207-736) mg/day. Of 46 evaluable patients, 18 achieved an optimal response and 28 did not. Of the latter, nine patients underwent dose escalation to 400 mg BID, and none achieved MR4.5 . The remaining 19 patients could not undergo dose escalation, 12 (63%) because of adverse events (AEs), and 7 (37%) for non-AE related reasons. Four of these patients achieved MR4.5 . The MR4.5 rate by 24 months was 45.7%. The progression-free, overall and event-free survival were each 97.6%. No new safety concerns were observed. Our findings support the use of continuous nilotinib at a dose of 300 mg BID for newly diagnosed patients with CML-CP.


Subject(s)
Leukemia, Myeloid, Chronic-Phase/drug therapy , Pyrimidines/standards , Pyrimidines/therapeutic use , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Leukemia, Myeloid, Chronic-Phase/pathology , Male , Middle Aged , Non-Randomized Controlled Trials as Topic , Prognosis , Survival Rate , Young Adult
19.
Cancer Med ; 9(5): 1694-1702, 2020 03.
Article in English | MEDLINE | ID: mdl-31950647

ABSTRACT

Lenalidomide is an immunomodulatory drug that is administered commonly in patients with relapsed or refractory multiple myeloma (RRMM). Eosinophils have immunological functions, for instance, in allergic diseases and asthma. The purpose of this study was to investigate the clinical significance of elevated eosinophil levels in patients with RRMM treated with lenalidomide. A total of 59 patients were included. Elevated eosinophil level was defined as an increase in the eosinophil count of ≥250/µL from the eosinophil count on day 1 during the first cycle. The percentage of patients with elevated eosinophil levels was 22.0%. The overall response ratio in the elevated eosinophil group and nonelevated eosinophil group was 84.6% and 63.0% (P = .189), respectively. The median time to next treatment (TTNT) in the elevated eosinophil group was significantly longer than that in the nonelevated group (40.3 months vs 8.4 months; P = .017). Additionally, TTNT in the elevated eosinophil group with partial response (PR) or better was significantly longer than that in the nonelevated eosinophil group with PR or better (40.3 months vs 11.9 months; P = .021). We concluded that elevated eosinophil levels were frequently observed and might predict a longer TTNT in patients with RRMM treated with lenalidomide.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Eosinophils/immunology , Lenalidomide/administration & dosage , Multiple Myeloma/drug therapy , Neoplasm Recurrence, Local/drug therapy , Time-to-Treatment/statistics & numerical data , Aged , Aged, 80 and over , Disease Progression , Drug Resistance, Neoplasm/immunology , Female , Follow-Up Studies , Humans , Leukocyte Count , Male , Middle Aged , Multiple Myeloma/blood , Multiple Myeloma/immunology , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/immunology , Predictive Value of Tests , Prognosis , Retrospective Studies , Time Factors
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