[Sequential therapy with inotuzumab ozogamicin followed by CAR T-cell therapy for Philadelphia chromosome-negative acute lymphoblastic leukemia].

A 25-year-old woman with a history of B-cell acute lymphoblastic leukemia over ten years ago was referred to our hospital with a chief complaint of leukoblastosis. She was participating in a JPLSG (Japanese Pediatric Leukemia/Lymphoma Study Group) clinical study at that time. We diagnosed ALL relapse by multi-color flow cytometric analysis of bone marrow samples at admission, with reference to previous JPLSG data. Because her leukemic cells were resistant to conventional cytotoxic agents, she proceeded to lymphocyte apheresis for chimeric antigen receptor T-cell (CAR-T, Tisagenlecleucel [Tisa-cel]). She received two cycles of inotuzumab ozogamicin as a bridging therapy to Tisa-cel, resulting in a hematological complete remission (minimal residual disease measured by polymerase chain reaction [PCR-MRD] was positive at 1.0×10-4). She was finally administered Tisa-cel and achieved MRD negativity. She is currently in complete remission with careful MRD monitoring. This strategy of sequential bi-targeted therapy combining antibody conjugates and CAR-T cells provides tumor control in deeper remission and minimal damage to organ function through reduced use of cytotoxic anti-tumor agents. Therefore, we believe that this therapeutic strategy is an effective and rational treatment for adolescent and young adult ALL patients.

First complete remission favours haploidentical haematopoietic stem cell transplantation with post-transplant cyclophosphamide over cord blood transplantation in acute lymphoblastic leukaemia.

To assess the benefits of HLA-haploidentical haematopoietic stem cell transplantation using post-transplant cyclophosphamide (PTCy-haplo) relative to those of umbilical cord blood (UCB) transplantation in acute lymphoblastic leukaemia (ALL), we analysed 1999 patients (PTCy-haplo, 330; UCB, 1669), using the nationwide Japanese registry. PTCy-haplo was associated with a significantly higher relapse rate, but lower non-relapse mortality, which results in overall survival and disease-free survival, comparable to those of UCB. Among patients in CR1, PTCy-haplo showed a significantly higher survival than UCB regardless of the CD34+ cell dose. Our findings provide valuable insights into the donor selection algorithm in allogeneic HSCT for adult patients with ALL.

Successful Bridging to Allogeneic Hematopoietic Stem Cell Transplantation by Azacitidine and Venetoclax in a Case of Acute Myeloid Leukemia With t(3;3)(q21.3;q26.2) Developed Early After Orthotopic Heart Transplantation.

A 48-year-old male patient developed acute myeloid leukemia (AML) with t(3;3)(q21.3;q26.2) chromosomal mutation 8 months after orthotopic heart transplantation from a human leukocyte antigen-unmatched brain-dead donor for cardiac sarcoidosis. He had sequelae of stroke and chronic renal failure at the time of AML diagnosis. He received 3 cycles of azacitidine and venetoclax induction therapy and achieved complete hematological remission with incomplete count recovery without causing severe complications, including infection. He sequentially underwent allogeneic peripheral blood stem cell transplantation from a HLA-8/8 matched, ABO-blood matched, unrelated female donor and successfully achieved donor cell engraftment. His transplanted heart was viable, and the coronary vessels were not damaged even after allogeneic peripheral blood stem cell transplantation. Although AML relapsed afterward, azacytidine/venetoclax was a tolerable bridging therapy even for early-onset AML after heart transplantation.

[Acquired hemophilia A following BNT162b2 mRNA COVID-19 vaccination].

Acquired hemophilia A (AHA) is a rare disease characteized by bleeding symptoms caused by decreased factor VIII activity due to the appearance of inhibitors to factor VIII triggered by malignancy or collagen disease. An 86-year-old woman developed purpura on her extremities after the first dose of the BNT162b2 mRNA COVID-19 vaccine. This symptom subsided after a few days. After the second dose of the BNT162b2 mRNA COVID-19 vaccine, purpura appeared again, and the patient was referred to our hospital Her APTT was remarkably prolonged to 110 seconds, and a cross-mixing test revealed an inhibitor pattern. Since FVIII activity was <1% and FVIII inhibitor was 51.6 BU, she was diagnosed with AHA. Prednisolone therapy was started, and coagulative complete remission was achieved. Because acquired hemophilia can develop after mRNA COVID-19 vaccination, as in this case, it is critical to monitor the appearance of bleeding symptom.

Prolonged gut microbial alterations in post-transplant survivors of allogeneic haematopoietic stem cell transplantation.

Dysbiosis of the gut microbiota has been reported to increase early complications after allogeneic haematopoietic stem cell transplantation (allo-HSCT). However, it remains unclear whether gut microbial alterations persist during late complications, such as chronic graft-versus-host disease (cGVHD) or secondary cancers. Here, we analysed the gut microbiota of 59 patients who survived for 1-21.7 years (median, 6.4 years) after allo-HSCT. Long-term survivors showed lower gut microbial diversity than the age- and sex-matched healthy controls. This decreased diversity was reflected in the reduced abundance of the butyrate-producing bacteria. Patients with a history of grade 3 acute graft-versus-host disease (aGVHD) exhibited higher Veillonella abundance than patients with a history of grade 1-2 or non-aGVHD cases. The abundance of Faecalibacterium showed no decrease only in limited cGVHD cases. Additionally, the microbial structure in the secondary cancer group was significantly different (p < 0.05) from that in the non-secondary cancer group. This study is the first to show that microbial dysbiosis is present over a 10-year lifetime after discharge following allo-HSCT. Our results suggest that these prolonged gut microbial alterations may be associated with the development and exacerbation of late complications in post-transplant survivors.

Special AT-Rich Sequence-Binding Protein 1 Supports Survival and Maturation of Naive B Cells Stimulated by B Cell Receptors.

Epigenetic mechanisms underpin the elaborate activities of essential transcription factors in lymphocyte development. Special AT-rich sequence-binding protein 1 (SATB1) is a chromatin remodeler that orchestrates the spatial and temporal actions of transcription factors. Previous studies have revealed the significance of SATB1 in T cell lineage. However, whether and how SATB1 controls B cell lineage development is yet to be clarified. In this study, we show that SATB1 is an important factor during splenic B cell maturation. By analyzing SATB1/Tomato reporter mice, we determined the dynamic fluctuation of SATB1 expression in the B cell lineage. Although SATB1 expression decreased to minimal levels during B cell differentiation in the bone marrow, it resurged markedly in naive B cells in the spleen. The expression was dramatically downregulated upon Ag-induced activation. Splenic naive B cells were subdivided into two categories, namely SATB1high and SATB1-/low, according to their SATB1 expression levels. SATB1high naive B cells were less susceptible to death and greater proliferative than were SATB1-/low cells during incubation with an anti-IgM Ab. Additionally, SATB1high cells tended to induce the expression of MHC class II, CD86, and CD83. Accordingly, naive B cells from B lineage-specific SATB1 conditional knockout mice were more susceptible to apoptosis than that in the control group upon anti-IgM Ab stimulation in vitro. Furthermore, conditional knockout mice were less capable of producing Ag-specific B cells after immunization. Collectively, our findings suggest that SATB1 expression increases in naive B cells and plays an important role in their survival and maturation.

Inotuzumab ozogamicin and blinatumomab sequential therapy for relapsed/refractory Philadelphia chromosome-positive acute lymphoblastic leukemia.

To overcome the unfavorable outcome of refractory/relapsed (R/R) Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) and conduct allogeneic stem cell transplantation (allo-SCT) safely, we designed a sequential therapy involving a single cycle of Inotuzumab ozogamicin (InO) and Blinatumomab (Blina). Two heavily treated and aged patients with R/R Ph+ALL were treated with the therapy. Both of them achieved complete molecular remission without cytokine release syndrome and underwent allo-SCT without veno-occlusive disease/sinusoidal obstruction syndrome. Although appropriate central nervous system prophylaxis should be added, the InO-Blina sequential therapy is a promising strategy for treating R/R Ph+ALL as a bridging regimen before allo-SCT.

Clinical implications of combination therapy with quizartinib and craniospinal irradiation for refractory acute myeloid leukemia positive for FMS-like tyrosine kinase 3-internal tandem duplication with central nervous system involvement.

FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation-positive acute myeloid leukemia (AML) has a poor prognosis. We report the first case of successful bridge therapy of novel FLT3 inhibitor, quizartinib, to umbilical cord blood stem cell transplantation for FLT3-ITD-positive AML-primary induction failure patients with central nervous system involvement.

Passive immune basophil activation test for the identification of allergic episodes from various adverse events elicited by haematopoietic cell transplantation: A pilot study.

BACKGROUND AND OBJECTIVES: Haematopoietic cell transplantation (HCT) therapy tends to be associated with various complications including engraftment failure, regimen-related toxicities, and infectious diseases. In addition, HC infusion itself occasionally elicits adverse events (AEs), one of the most common AEs is an allergic reaction. As appropriate laboratory tests have not yet been established to distinguish allergy-mediated AEs from other complications, clinical responses for HCT-related AEs can only be nonspecific. In this pilot study, using passive immune basophil activation test (pi-BAT), we attempted to distinguish an HC infusion-induced allergic reaction from various HCT-related AEs. MATERIALS AND METHODS: Using pi-BAT, we examined 34 patients who underwent HCT, that is, 11 with AEs and 23 without AEs as controls. RESULTS: Two of the eleven AE cases were pi-BAT positive and, the rest of nine AE cases were negative, while all non-AE cases were negative. Both of the two positive cases showed erythema, tachycardia, plus cough. Because erythema is one of the representative symptom of allergy, those cases could be classified as allergic reaction cases or anaphylaxis cases if tachycardia and cough were concomitant symptoms of erythema. Among the nine AEs with pi-BAT negative result, four cases showed urticaria, four showed vomiting plus diarrhoea, and one showed cough. Urticaria case was strongly suspected of allergy, however, the AE cases were pi-BAT negative. CONCLUSION: The pi-BAT may be useful as an auxiliary diagnostic tool to confirm the possible involvement of HC infusion in HCT-related AEs and identify an immunologic mechanism for HCT-related hypersensitivity reactions.

Autonomous TGFß signaling induces phenotypic variation in human acute myeloid leukemia.

Heterogeneity of leukemia stem cells (LSCs) is involved in their collective chemoresistance. To eradicate LSCs, it is necessary to understand the mechanisms underlying their heterogeneity. Here, we aimed to identify signals responsible for heterogeneity and variation of LSCs in human acute myeloid leukemia (AML). Monitoring expression levels of endothelial cell-selective adhesion molecule (ESAM), a hematopoietic stem cell-related marker, was useful to detect the plasticity of AML cells. While healthy human hematopoietic stem/progenitor cells robustly expressed ESAM, AML cells exhibited heterogeneous ESAM expression. Interestingly, ESAM- and ESAM+ leukemia cells obtained from AML patients were mutually interconvertible in culture. KG1a and CMK, human AML clones, also represented the heterogeneity in terms of ESAM expression. Single cell culture with ESAM- or ESAM+ AML clones recapitulated the phenotypic interconversion. The phenotypic alteration was regulated at the gene expression level, and RNA sequencing revealed activation of TGFß signaling in these cells. AML cells secreted TGFß1, which autonomously activated TGFß pathway and induced their phenotypic variation. Surprisingly, TGFß signaling blockade inhibited not only the variation but also the proliferation of AML cells. Therefore, autonomous activation of TGFß signaling underlies the LSC heterogeneity, which may be a promising therapeutic target for AML.

Limbic encephalitis with antibodies to N-methyl-D-aspartate (NMDA)-type glutamate receptor after allogeneic transplantation.

Various central nervous system (CNS) complications may occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which can result in severe clinical problems. Diagnosis is often difficult, as distinctive clinical symptoms may be absent and different neurological disorders may exhibit similar symptoms. Despite the fact that antibodies responding to brain cell surface antigens have become well recognized in several CNS disorders, cases of autoimmune CNS disorders after allo-HSCT have rarely been reported. Here, we report on a patient who developed encephalitis associated with antibodies against N-methyl-D-aspartate (NMDA)-type glutamate receptor (GluR) after allo-HSCT. To the best of our knowledge, this is the first report of the involvement of antibodies against NMDA-type GluR in post-transplantation encephalitis. Autoimmunity to NMDA-type GluR may have contributed to neurological complications after transplantation in unresolved cases.

Curative potential of fludarabine, melphalan, and non-myeloablative dosage of busulfan in elderly patients with myeloid malignancy.

Although the combination of fludarabine and high-dose melphalan (FLU/MEL) has been widely used in allogeneic stem cell transplantation, high-dose MEL causes life-threatening adverse events, especially in elderly patients. To reduce the toxicity of MEL without losing its antileukemic effect, we formulated a regimen comprising FLU (125 mg/m2), MEL (100 mg/m2), and a non-myeloablative busulfan dosage [4 mg/kg orally (oral) or 3.2 mg/kg intravenously (iv); FLU/MEL/BU]. We retrospectively analyzed 32 patients with myeloid malignancies who received FLU/MEL/BU at our institute. Median age was 59 years and the median observation period after allo-SCT was 8.2 years. The disease status of most of the patients (97%) at transplantation was controlled. The rate of neutrophil engraftment was 93.3%. The 5-year overall survival (OS), disease-free survival (DFS), non-relapse mortality (NRM), and relapse rate (RR) were 68.5%, 62.1%, 22.0%, and 15.9%, respectively, in all patients. Notably, the outcome of FLU/MEL/iv BU was excellent, with the 5-year OS and DFS being 75.6% and 70.8%, respectively, accompanied by a reduced 5-year NRM and RR of 19.3% and 9.8%, respectively. In conclusion, FLU/MEL/BU, particularly FLU/MEL/iv BU, has curative potential for controlled myeloid malignancies.

Endothelial Cell-Selective Adhesion Molecule Contributes to the Development of Definitive Hematopoiesis in the Fetal Liver.

Endothelial cell-selective adhesion molecule (ESAM) is a lifelong marker of hematopoietic stem cells (HSCs). Although we previously elucidated the functional importance of ESAM in HSCs in stress-induced hematopoiesis in adults, it is unclear how ESAM affects hematopoietic development during fetal life. To address this issue, we analyzed fetuses from conventional or conditional ESAM-knockout mice. Approximately half of ESAM-null fetuses died after mid-gestation due to anemia. RNA sequencing analyses revealed downregulation of adult-type globins and Alas2, a heme biosynthesis enzyme, in ESAM-null fetal livers. These abnormalities were attributed to malfunction of ESAM-null HSCs, which was demonstrated in culture and transplantation experiments. Although crosslinking ESAM directly influenced gene transcription in HSCs, observations in conditional ESAM-knockout fetuses revealed the critical involvement of ESAM expressed in endothelial cells in fetal lethality. Thus, we showed that ESAM had important roles in developing definitive hematopoiesis. Furthermore, we unveiled the importance of endothelial ESAM in this process.

Addition of melphalan to fludarabine/busulfan (FLU/BU4/MEL) provides survival benefit for patients with myeloid malignancy following allogeneic bone-marrow transplantation/peripheral blood stem-cell transplantation.

A conditioning regimen with fludarabine and myeloablative dose of busulfan (FLU/BU4) has been commonly used in allogeneic hematopoietic cell transplantation (allo-HCT). However, there are two major problems with this regimen: insufficient anti-leukemic effect, especially in advanced cases, and slow time to complete donor-type chimerism, especially T-cell chimerism. To overcome these issues, we designed a combination regimen with FLU (150 mg/m2), intravenous BU (12.8 mg/kg), and melphalan (100 mg/m2) (FLU/BU4/MEL) and conducted retrospective analyses of treatment outcomes at our institute. Forty-two patients with myeloid malignancies received allogeneic bone-marrow transplantation or peripheral blood stem-cell transplantation (allo-BMT/PBSCT) with FLU/BU4/MEL regimen. The median age of patients was 46.5 years (20-63 years). Thirteen patients (31%) did not achieve complete hematological remission at transplantation. All patients examined achieved complete whole and T-cell chimerism within 1 month after allo-HCT. The 4-year overall survival and disease-free survival rates were 66.0% [95% confidence interval (CI) 49.4-78.3%] and 59.5% (95% CI 43.2-72.6%) in all patients, and 49.4% (95% CI 19.7-73.6%) and 38.5% (95% CI 14.1-62.8%) in patients who were not in remission. In conclusion, FLU/BU4/MEL showed curative potential, even in patients with advanced myeloid malignancies, accompanied by achievement of rapid complete chimerism after allo-BMT/PBSCT.

Variable SATB1 Levels Regulate Hematopoietic Stem Cell Heterogeneity with Distinct Lineage Fate.

Hematopoietic stem cells (HSCs) comprise a heterogeneous population exhibiting self-renewal and differentiation capabilities; however, the mechanisms involved in maintaining this heterogeneity remain unclear. Here, we show that SATB1 is involved in regulating HSC heterogeneity. Results in conditional Satb1-knockout mice revealed that SATB1 was important for the self-renewal and lymphopoiesis of adult HSCs. Additionally, HSCs from Satb1/Tomato-knockin reporter mice were classified based on SATB1/Tomato intensity, with transplantation experiments revealing stronger differentiation toward the lymphocytic lineage along with high SATB1 levels, whereas SATB1- HSCs followed the myeloid lineage in agreement with genome-wide transcription and cell culture studies. Importantly, SATB1- and SATB1+ HSC populations were interconvertible upon transplantation, with SATB1+ HSCs showing higher reconstituting and lymphopoietic potentials in primary recipients relative to SATB1- HSCs, whereas both HSCs exhibited equally efficient reconstituted lympho-hematopoiesis in secondary recipients. These results suggest that SATB1 levels regulate the maintenance of HSC multipotency, with variations contributing to HSC heterogeneity.

Identification of MS4A3 as a reliable marker for early myeloid differentiation in human hematopoiesis.

Information of myeloid lineage-related antigen on hematopoietic stem/progenitor cells (HSPCs) is important to clarify the mechanisms regulating hematopoiesis, as well as for the diagnosis and treatment of myeloid malignancies. We previously reported that special AT-rich sequence binding protein 1 (SATB1), a global chromatin organizer, promotes lymphoid differentiation from HSPCs. To search a novel cell surface molecule discriminating early myeloid and lymphoid differentiation, we performed microarray analyses comparing SATB1-overexpressed HSPCs with mock-transduced HSPCs. The results drew our attention to membrane-spanning 4-domains, subfamily A, member 3 (Ms4a3) as the most downregulated molecule in HSPCs with forced overexpression of SATB1. Ms4a3 expression was undetectable in hematopoietic stem cells, but showed a concomitant increase with progressive myeloid differentiation, whereas not only lymphoid but also megakaryocytic-erythrocytic progenitors were entirely devoid of Ms4a3 expression. Further analysis revealed that a subset of CD34+CD38+CD33+ progenitor population in human adult bone marrow expressed MS4A3, and those MS4A3+ progenitors only produced granulocyte/macrophage colonies, losing erythroid colony- and mixed colony-forming capacity. These results suggest that cell surface expression of MS4A3 is useful to distinguish granulocyte/macrophage lineage-committed progenitors from other lineage-related ones in early human hematopoiesis. In conclusion, MS4A3 is useful to monitor early stage of myeloid differentiation in human hematopoiesis.

Endothelial Cell-Selective Adhesion Molecule Expression in Hematopoietic Stem/Progenitor Cells Is Essential for Erythropoiesis Recovery after Bone Marrow Injury.

Numerous red blood cells are generated every second from proliferative progenitor cells under a homeostatic state. Increased erythropoietic activity is required after myelo-suppression as a result of chemo-radio therapies. Our previous study revealed that the endothelial cell-selective adhesion molecule (ESAM), an authentic hematopoietic stem cell marker, plays essential roles in stress-induced hematopoiesis. To determine the physiological importance of ESAM in erythroid recovery, ESAM-knockout (KO) mice were treated with the anti-cancer drug, 5-fluorouracil (5-FU). ESAM-KO mice experienced severe and prolonged anemia after 5-FU treatment compared to wild-type (WT) mice. Eight days after the 5-FU injection, compared to WT mice, ESAM-KO mice showed reduced numbers of erythroid progenitors in bone marrow (BM) and spleen, and reticulocytes in peripheral blood. Megakaryocyte-erythrocyte progenitors (MEPs) from the BM of 5-FU-treated ESAM-KO mice showed reduced burst forming unit-erythrocyte (BFU-E) capacities than those from WT mice. BM transplantation revealed that hematopoietic stem/progenitor cells from ESAM-KO donors were more sensitive to 5-FU treatment than that from WT donors in the WT host mice. However, hematopoietic cells from WT donors transplanted into ESAM-KO host mice could normally reconstitute the erythroid lineage after a BM injury. These results suggested that ESAM expression in hematopoietic cells, but not environmental cells, is critical for hematopoietic recovery. We also found that 5-FU treatment induces the up-regulation of ESAM in primitive erythroid progenitors and macrophages that do not express ESAM under homeostatic conditions. The phenotypic change seen in macrophages might be functionally involved in the interaction between erythroid progenitors and their niche components during stress-induced acute erythropoiesis. Microarray analyses of primitive erythroid progenitors from 5-FU-treated WT and ESAM-KO mice revealed that various signaling pathways, including the GATA1 system, were impaired in ESAM-KO mice. Thus, our data demonstrate that ESAM expression in hematopoietic progenitors is essential for erythroid recovery after a BM injury.

ESAM is a novel human hematopoietic stem cell marker associated with a subset of human leukemias.

Reliable markers are essential to increase our understanding of the biological features of human hematopoietic stem cells and to facilitate the application of hematopoietic stem cells in the field of transplantation and regenerative medicine. We previously identified endothelial cell-selective adhesion molecule (ESAM) as a novel functional marker of hematopoietic stem cells in mice. Here, we found that ESAM can also be used to purify human hematopoietic stem cells from all the currently available sources (adult bone marrow, mobilized peripheral blood, and cord blood). Multipotent colony-forming units and long-term hematopoietic-reconstituting cells in immunodeficient mice were found exclusively in the ESAM(High) fraction of CD34(+)CD38(-) cells. The CD34(+)CD38(-) fraction of cord blood and collagenase-treated bone marrow contained cells exhibiting extremely high expression of ESAM; these cells are likely to be related to the endothelial lineage. Leukemia cell lines of erythroid and megakaryocyte origin, but not those of myeloid or lymphoid descent, were ESAM positive. However, high ESAM expression was observed in some primary acute myeloid leukemia cells. Furthermore, KG-1a myeloid leukemia cells switched from ESAM negative to ESAM positive with repeated leukemia reconstitution in vivo. Thus, ESAM is a useful marker for studying both human hematopoietic stem cells and leukemia cells.

[Diffuse large B-cell lymphoma occurring in a Waldenström macroglobulinemia patient with central nervous system infiltration].

The rare central nervous system (CNS) infiltration of Waldenström macroglobulinemia (WM) is known as Bing-Neel syndrome (BNS). Furthermore, the transformation of WM into diffuse large B-cell lymphoma (DLBCL) is also unusual. Herein, we report a 69-year-old male with DLBCL transformed from BNS. In November 2008, the patient visited a prior hospital because of anemia and was diagnosed with WM. After receiving chemotherapy (R-CHOP), his serum immunoglobulin M (IgM) level decreased and then remained at approximately 2000 mg/dl for 3 years. In November 2011, he complained of visual impairment and photophobia in his left eye. Magnetic resonance imaging showed enlargement of the left optic nerve and cerebrospinal fluid examination indicated CNS infiltration of WM cells. Consequently, he was diagnosed with BNS. He thus received CNS targeted chemotherapy (R-MPV) and achieved a partial response. In May 2014, IgM was elevated and swelling of systemic lymph nodes was detected. Inguinal lymph node biopsy yielded a pathological diagnosis of DLBCL and the clonality of tumor cells between WM and DLBCL was confirmed by the allele-specific oligonucleotide polymerase chain reaction (ASO-PCR).

Bifurcation phenomena of two self-propelled camphor disks on an annular field depending on system length.

Mode selection and bifurcation of a synchronized motion involving two symmetric self-propelled objects in a periodic one-dimensional domain were investigated numerically and experimentally by using camphor disks placed on an annular water channel. Newton's equation of motion for each camphor disk, whose driving force was the difference in surface tension, and a reaction-diffusion equation for camphor molecules on water were used in the numerical calculations. Among various dynamical behaviors found numerically, four kinds of synchronized motions (reversal oscillation, stop-and-move rotation, equally spaced rotation, and clustered rotation) were also observed in experiments by changing the diameter of the water channel. The mode bifurcation of these motions, including their coexistence, were clarified numerically and analytically in terms of the number density of the disk. These results suggest that the present mathematical model and the analysis of the equations can be worthwhile in understanding the characteristic features of motion, e.g., synchronization, collective motion, and their mode bifurcation.