Effectiveness of knee pad as an additional device for wheelchairs in improving upper-limb dexterity during seated tasks: a pilot study.

[Purpose] This study aimed to examine how supporting the knee from the front with a knee pad affected upper-limb dexterity while sitting. [Participants and Methods] A total of 14 healthy adult males were included in the study. As a measure of upper-limb dexterity, the number of pins was counted when the Purdue pegboard test was performed for 60 seconds. In addition, the ease of task performance was assessed using the visual analogue scale. There were two experimental conditions, with and without knee pad. The paired t-test was used to detect differences between the two conditions. A p-value of 0.05 was considered statistically significant. [Results] The Purdue pegboard test was 29.4 ± 2.5 and 27.9 ± 3.6 pins with and without knee pad, respectively. The VAS was 76.1 ± 10.3 and 62.9 ± 14.1 with and without knee pad, respectively. Both measured values were significantly higher with knee pad than without. [Conclusion] Supporting the knees from the front with knee pad improves upper-limb functionality while sitting, making it easier to perform seated tasks.

Polaprezinc for prevention of oral mucositis in patients receiving chemotherapy followed by hematopoietic stem cell transplantation: A multi-institutional randomized controlled trial.

Oral mucositis is a common and distressing complication in patients receiving high-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT). We reported previously in a single-center retrospective analysis that zinc-L-carnosine (polaprezinc [PZ]) reduced the incidence of oral mucositis associated with HSCT. To verify the accuracy of the prophylactic effect of PZ against oral mucositis, we carried out a multi-institutional prospective randomized controlled study. Patients were randomly allocated to either the prevention group, in which PZ lozenge treatment was started before chemotherapy, or the control group, in which administration of PZ lozenges was initiated immediately after the onset of Grade 2 oral mucositis. Oral mucositis was evaluated daily from the start of chemotherapy to 35 days after transplantation. A total of 91 patients were enrolled, and 88 patients (47 in the control group and 41 in the prevention group) were eligible for data analysis. The incidence of Grade ≥2 but not Grade ≥3 oral mucositis was significantly reduced in the prevention group compared to the control group (44.7% in control group vs 22.0% in the prevention group, P = .025). There were no significant differences in the incidence rates of other adverse events or the rate of engraftment (95.6% vs 97.2%, P = .693) between the two groups. These findings suggest that PZ lozenge is effective for prophylaxis against Grade ≥2 oral mucositis associated with chemotherapy in patients undergoing HSCT without any influence on the HSCT outcome.

Randomised phase II study to optimise melphalan, prednisolone, and bortezomib in untreated multiple myeloma (JCOG1105).

We conducted a randomised phase II study to determine the optimal dose and schedule of melphalan, prednisone, and bortezomib (MPB) (jRCTs031180097). Transplant-ineligible untreated multiple myeloma patients were randomised to Arm A (twice weekly bortezomib in one six-week cycle followed by eight five-week cycles of four times once weekly bortezomib with melphalan and prednisolone on days 1-4) or Arm B (nine four-week cycles of three times once weekly bortezomib with melphalan and prednisolone on days 1-4). The primary end-point was complete response (CR) rate. Of 91 patients randomised to two arms, 88 were eligible. The median cumulative bortezomib doses were 45·8 and 35·1 mg/m2 , CR rate was 18·6% [95% confidence interval (CI) 8·4-33·4] and 6·7% (95% CI 1·4-18·3), and the median progression-free survival (PFS) was 2·5 and 1·4 years in Arms A and B [hazard ratio (HR) 1·93 (95% CI 1·09-3·42)], respectively. Frequent grade ≥3 haematologic toxicities in Arms A and B were neutropenia (64·4% vs. 28·3%) and thrombocytopenia (35·6% vs. 10·9%). Grade 2/3 peripheral neuropathy was observed in 24·4/2·2% in Arm A and 8·7/0% in Arm B. In conclusion, Arm A was the more promising regimen, suggesting that the twice weekly schedule of bortezomib in the first cycle and higher cumulative dose of both bortezomib and melphalan influences the efficacy of modified MPB.

Effect of asymmetrical buttock pressure on forces exerted in buttock movement when using a reclining chair.

[Purpose] To clarify the effect of asymmetrical buttock pressure on the shear forces exerted on a buttock. [Participants and Methods] Sixteen healthy adult males participated in this study. A cushion 0 or 2 cm high was placed on the left side of the seat for all participants. The 0- and 2-cm height conditions were called "without difference condition" and "difference condition", respectively. The back support was inclined at increasing angles, starting at the upright position, to a fully reclined position, and back to the upright position. [Results] With the "difference condition", the force on the left buttock was 147.4% body weight and that on the right buttock was 105.6% body weight. In contrast, with the "without difference condition", there was no significant difference in the force on the left buttock and right buttock in terms of percent body weight. [Conclusion] Our results suggest that asymmetrical buttock pressure while in the sitting position causes a difference in shear force exerted on the left and right buttocks when using a reclining chair.

Investigation of the effect of a 15-degree tilt-in-space on the fluctuation of shear forces exerted on the buttocks when the back support is reclined.

[Purpose] This study aimed to investigate the effect of the combination of 15° tilt-in-space and recline angles on the fluctuation of shear forces exerted on the buttocks. [Participants and Methods] The participants were 11 healthy adult males. The parameters of the shear forces were the parallel and perpendicular forces exerted on the buttocks as measured by a force plate. The two conditions tested were T0R100-130 and T15R100-130. The tilt-in-space angles were set to 0° and 15° in the T0R100-130 and T15R100-130 conditions, respectively. The reclining angles were determined to be 100° to 130° in both conditions. [Results] Upon comparing the two conditions, the parallel and the perpendicular forces exerted on the buttocks in the T15R100-130 condition were significantly lower than those in the T0R100-130 condition in all positions of back support. Upon comparing the fluctuation values of the parallel and perpendicular forces, those applied in the T15R100-130 condition were significantly higher than those in the T0R100-130 condition. [Conclusion] These results suggest that the fluctuation of shear forces exerted on the buttocks could be decreased by using a combination of 15° tilt-in-space and reclining functions.

[Sarcoidosis-lymphoma syndrome showing abnormal FDG uptake in lymph nodes and muscles upon post-chemotherapy PET/CT imaging].

A 65-year-old woman was diagnosed with rheumatoid arthritis in 2010 and was treated with methotrexate (MTX). In 2012, she was diagnosed with sarcoidosis and underwent a follow-up therapy for mild peripheral neuropathy due to neurosarcoidosis. In 2018, she experienced primary splenic diffuse large B-cell lymphoma (DLBCL) and was diagnosed with sarcoidosis-lymphoma syndrome (SLS). MTX was discontinued, and six cycles of rituximab were administered combined with chemotherapy. Positron emission tomography combined with computed tomography performed 18 weeks after the last cycle of chemotherapy showed new abnormal fluoro-2-deoxy-D-glucose (FDG) uptake in the mediastinal and hilar lymph nodes and skeletal muscles. Sarcoidosis was suspected because of increased serum angiotensin-converting enzyme levels and magnetic resonance imaging findings in the lower limb muscles. However, pathological findings of DLBCL and sarcoidosis were not confirmed in the hilar lymph node biopsy. Therefore, malignant lymphoma can be distinguished from sarcoidosis using abnormal FDG uptake after chemotherapy for SLS.

Decreased level of phosphatidylcholine (16:0/20:4) in multiple myeloma cells compared to plasma cells: a single-cell MALDI-IMS approach.

Lipid metabolic changes under diseased conditions, particularly in solid tumors, are attracting increased attention. However, in non-solid tumors, including most hematopoietic tumors, lipid analyses are scarce. Multiple myeloma (MM) is a plasma cell disorder arising from bone marrow, and the lipid status of MM cells has not been reported yet. In this study, we analyzed flow cytometry-sorted single MM cells and normal plasma cells (NPCs) using matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS), a two-dimensional label-free mass spectrometry technique for biomolecular analysis, to obtain specific lipid information. We isolated 1.31-5.77% of MM cells and 0.03-0.24% of NPCs using fluorescence-activated cell sorting (FACS). Analysis of purified cells using MALDI-IMS at the single-cell level revealed that the peak intensity and ion signals of phosphatidylcholine [PC (16:0/20:4) + H](+) at m/z 782.5 were significantly decreased in MM cells compared to NPCs. By examining particular cell populations rather than cell mixtures, our method can become a suitable tool for the analysis of rare cell populations at the single-cell level and advance the understanding of MM progression.

Acquired factor X deficiency developed four years after autologous transplantation in a patient with multiple myeloma associated with systemic AL amyloidosis.

We describe a case of acquired factor X deficiency after high-dose melphalan with autologous stem cell transplantation (HDM/ASCT) for multiple myeloma (MM) with systemic AL amyloidosis. A 68-year-old woman with renal amyloidosis was diagnosed as having MM in 2007. She achieved a partial response after VAD (vincristine, adriamycin, dexamethasone) therapy and HDM/ASCT. In December 2011, coagulation tests revealed a prolonged prothrombin time (PT) of 17.6 sec and she was administered vitamin K. In January 2012, she received low anterior resection with colostomy for rectal cancer. She received fresh frozen plasma (FFP) infusion but the perioperative bleeding tendency persisted. In February 2012, she was referred from surgery for colostomy closure. She showed no progression of MM and had prolonged PT, corrected by mixing with normal plasma. Factor X activity was markedly decreased. She was diagnosed as having an acquired factor X deficiency and was given FFP infusion for colostomy closure. Although acquired factor X deficiency after HDM/ASCT for MM with systemic AL amyloidosis is rare, we should be aware of the possibility of this disease in MM patients with a bleeding tendency.

JmjC-domain containing histone demethylase 1B-mediated p15(Ink4b) suppression promotes the proliferation of leukemic progenitor cells through modulation of cell cycle progression in acute myeloid leukemia.

The histone demethylase JHDM1B has been implicated in cell cycle regulation and tumorigenesis. In addition, it has been reported that JHDM1B is highly expressed in various human tumors, including leukemias. However, it is not clearly understood how JHDM1B contributes to acute myeloid leukemia (AML) cell proliferation. In this study, we investigated the cellular and molecular function of JHDM1B in AML cells. In AML cell lines and AML-derived ALDH(hi) (high aldehyde dehydrogenase activity)/CD34(+) cells, the levels of JHDM1B mRNA were significantly higher than in normal ALDH(hi) /CD34(+) cells. Reduction of JHDM1B expression in AML cells inhibited cell proliferation compared to control cells, through induction of G1 cell cycle arrest, an increase in the p15(Ink4b) mRNA and protein expression. JHDM1B mRNA was overexpressed in all 133 AML clinical specimens tested (n = 22, 57, 34, and 20 for M1, 2, 4, and 5 subtypes respectively). Compared to normal ALDH(hi) /CD34(+) cells, JHDM1B gene expression was 1.57- to 1.87-fold higher in AML-derived ALDH(hi) /CD34(+) cells. Moreover, the JHDM1B protein was more strongly expressed in AML-derived ALDH(hi) /CD34(+) cells from compared to normal ALDH(hi) /CD34(+) cells. In addition, depletion of JHDM1B reduced colony formation of AML-derived ALDH(hi) /CD34(+) cells due to induction of p15(Ink4b) expression through direct binding to p15(Ink4b) promoter and loss of demethylation of H3K36me2. In summary, we found that JHDM1B mRNA is predominantly expressed in AML-derived ALDH(hi) /CD34(+) cells, and that aberrant expression of JHDM1B induces AML cell proliferation through modulation of cell cycle progression. Thus, inhibition of JHDM1B expression represents an attractive target for AML therapy.

Effect of shape of back support adjustment on shear force applied to buttocks when tilt-in-space and reclining functions are combined in wheelchairs.

PURPOSE: This study aimed to investigate the effect of the shape of the back support adjustment on the shear force applied to the buttocks when tilt-in-space and reclining functions are combined in wheelchairs. MATERIALS AND METHODS: Fourteen healthy adult men were included in the study. The force plate was used to measure the parallel force as shear force. The measurement posture, leaning against the back support of an experimental chair, was a comfortable sitting posture. The tilt-in-space angle was set to 15°. The back support was inclined at increasing angles, starting from the upright position (IUP), proceeding to a fully reclined position (FRP), and returning to the upright position (RUP). The experimental conditions were as follows: adjusting the back-support shape (aBS) and non-adjusting the back support shape (non-aBS). RESULTS: Positive values indicate a parallel force applied to the buttocks posteriorly. The average values in the aBS condition were 3.4 ± 2.3, 13.6 ± 2.2, and -7.1 ± 2.4% body weight in the IUP, FRP, and RUP, respectively. The average values in the non-aBS condition were 3.8 ± 2.5, 11.4 ± 2.1, and -6.2 ± 3.1% body weight in the IUP, FRP, and RUP, respectively. There were significant differences between the two conditions in FRP (p < 0.01). CONCLUSION: These findings suggest that the shape of the back support adjustment function increased the shear force applied to the buttocks posteriorly when the back support was inclined backwards using both the tilt-in-space and reclining functions.IMPLICATIONS FOR REHABILITATIONWhen utilizing both the tilt-in-space and reclining functions to incline the back support, the shear force applied to the buttocks is greatly affected by the shape of the back support.The shape of back support adjustment is a function that can stabilize elderly persons' sitting posture, but it may increase the external force applied to the buttocks and back.

Down-regulation of Thanatos-associated protein 11 by BCR-ABL promotes CML cell proliferation through c-Myc expression.

Bcr-Abl activates various signaling pathways in chronic myelogenous leukemia (CML) cells. The proliferation of Bcr-Abl transformed cells is promoted by c-Myc through the activation of Akt, JAK2 and NF-κB. However, the mechanism by which c-Myc regulates CML cell proliferation is unclear. In our study, we investigated the role of Thanatos-associated protein 11 (THAP11), which inhibits c-Myc transcription, in CML cell lines and in hematopoietic progenitor cells derived from CML patients. The induction of THAP11 expression by Abl kinase inhibitors in CML cell lines and in CML-derived hematopoietic progenitor cells resulted in the suppression of c-Myc. In addition, over-expression of THAP11 inhibited CML cell proliferation. In colony forming cells derived from CML-aldehyde dehydrogenase (ALDH)(hi) /CD34(+) cells, treatment with Abl kinase inhibitors and siRNA depletion of Bcr-Abl induced THAP11 expression and reduced c-Myc expression, resulting in inhibited colony formation. Moreover, overexpression of THAP11 significantly decreased the colony numbers, and also inhibited the expression of c-myc target genes such as Cyclin D1, ODC and induced the expression of p21(Cip1) . The depletion of THAP11 inhibited JAK2 or STAT5 inactivation-mediated c-Myc reduction in ALDH(hi) /CD34(+) CML cells. Thus, the induced THAP11 might be one of transcriptional regulators of c-Myc expression in CML cell. Therefore, the induction of THAP11 has a potential possibility as a target for the inhibition of CML cell proliferation.

An investigation into the effectiveness of a novel wheelchair seat-cover assembly for the reduction of forces exerted onto the buttocks.

PURPOSE: This purpose was to investigate developed seat-cover assemblies' effect on decreasing the fluctuation of the shear force exerted onto the buttocks as the factors causing decubitus ulcers when the back-support was inclined. MATERIALS AND METHODS: The participants were 10 wheelchair users. The force plate was used to measure the horizontal force as the shear force. The back-support was inclined at increasing angles, starting from the upright position (IUP), then proceeding to a fully reclined position (FRP), and returning to the upright position (RUP). The experimental conditions were two conditions; the seat-cover assembly conditions and without the seat-cover assembly as the control conditions. RESULTS: The average values in the seat-cover assembly condition were 14.4 ± 3.3, 13.9 ± 2.3, and 17.3 ± 3.3% body weight in the IUP, FRP, and RUP, respectively. The average values in the control condition were 14.8 ± 2.6, 11.4 ± 1.7, and 24.0 ± 6.7% body weight in the IUP, FRP, and RUP, respectively. In the FUP and the RUP, there were significant differences between two conditions (p < .01). CONCLUSION: These results suggested that the shear force exerted onto the buttocks may to be decreased by using novel seat-cover assembly.Implications for rehabilitationIt is possible to decrease the fluctuations in the shear force by moving the body up and down according the novel seat-cover assembly attached the back-support incline.Disabled, older individuals can be provided with a comfortable life on a reclining wheelchair while preventing decubitus ulcers.

Effect of Early Nutritional Support on Quality of Life by EORTC QLQ-C30 in Allogeneic Hematopoietic Stem Cell Transplantation.

Purpose: Increasing attention is being paid to the importance of nutritional management of allogeneic hematopoietic stem cell transplant (allo-HSCT) patients. However, few studies have conducted detailed evaluations of both nutritional intake and quality of life (QOL) in allo-HSCT patients. Therefore, we investigated the nutritional status and quality of life of our allo-HSCT patients. Methods: The subjects were 26 adults who underwent allo-HSCT at Hamamatsu University Hospital between August 2018 and October 2021. Early nutritional intervention was provided from the time of the decision to perform allo-HSCT to the time of discharge, and it incorporated regular QOL assessments. The analyzed indices were nutritional intake, anthropometric measurements, body mass index (BMI), grip strength, body composition analyzer (InBody S10) measurements, and blood laboratory values including transthyretin levels. QOL was assessed using the QLQ-C30 questionnaire of the European Organization for Research and Treatment of Cancer (EORTC) (version 3.0) and calculated according to the EORTC scoring manual. The indices were compared at pre-transplantation, 30 days post-transplantation, 60 days post-transplantation, and at discharge. The association between pre-transplantation nutritional status and QOL was examined. Results: The median hospital stay after transplantation was 97 days (range, 78-123 days). Energy intake was maintained at 31 kcal/day/kg through 30 days post-transplantation, 60 days post-transplantation, and discharge, and protein intake was maintained at 1.0 g/day/kg throughout all time periods. There was a significant positive correlation between the pre-transplantation transthyretin level and the 60-day post-transplantation QOL scores for "global health", "physical functioning", "cognitive functioning", and "emotional functioning", and there were significant negative correlations with "fatigue" and "pain" that indicated improvement. Conclusion: Early nutritional management of allo-HSCT patients prior to transplantation allowed maintenance of nutritional intake, and higher pre-transplant transthyretin levels were associated with higher QOL scores at 60 days post-transplantation.

Successful treatment with nilotinib after bosutinib-induced pulmonary arterial hypertension recurrence following dasatinib in chronic myeloid leukemia in chronic phase.

A 52-year-old man was diagnosed with chronic myeloid leukemia in the chronic phase (CML-CP). He experienced bosutinib-induced pulmonary arterial hypertension (PAH) recurrence following dasatinib use. Symptoms and examination findings associated with PAH improved after bosutinib cessation. Although nilotinib was started because of the loss of response after bosutinib cessation, a deep molecular response without PAH recurrence was achieved 3 months after the initiation of nilotinib therapy. PAH recurrence after switching to bosutinib due to dasatinib-induced PAH should be closely monitored. In addition, nilotinib therapy might be an effective approach in PAH cases related to dasatinib and/or bosutinib in patients with CML-CP.

Marked, Lasting Disease Regression and Concomitantly Induced Autoimmune Hemolytic Anemia and Hemophagocytic Lymphohistiocytosis in a Patient With Lung Adenocarcinoma and Autoantibodies Receiving Atezolizumab Plus Chemotherapy: A Case Report.

Various immune-related adverse events can frequently occur, which may be life-threatening if programmed death 1 or its ligand is blocked. Here, we report a rare case of concomitant autoimmune hemolytic anemia and hemophagocytic lymphohistiocytosis caused by atezolizumab plus chemotherapy in a patient with lung adenocarcinoma and autoantibodies. Dramatic and lasting tumor regression in response to only one therapy cycle was achieved. Nevertheless, this case suggests that careful management is required when using immunotherapy in patients with autoantibodies.

Small GTPase RAB45-mediated p38 activation in apoptosis of chronic myeloid leukemia progenitor cells.

Chronic myelogenous leukemia (CML) is characterized by a reciprocal chromosomal translocation (9;22) that generates the Bcr-Abl fusion gene. BCR-ABL transforming activity is mediated by critical downstream signaling pathways that are aberrantly activated by tyrosine kinases. However, the mechanisms of BCR-ABL anti-apoptotic effects and the signaling pathways by which BCR-ABL influences apoptosis in BCR-ABL-expressing cells are poorly defined. In this study, we found that treatment with ABL kinase inhibitors or depletion of BCR-ABL induced the expression of RAB45 messenger RNA and protein and induced apoptosis via reduction of mitochondrial membrane potential and p38 activation in CML cell lines and BCR-ABL(+) progenitor cells from CML patients. Overexpressed RAB45 induced the activation of caspases-3 and -9 and reduced the expression of Survivin, XIAP, c-IAP1 and c-IAP2 in CML cells. Moreover, in colony-forming cells derived from CML-aldehyde dehydrogenase(hi)/CD34(+) cells, treatment with ABL kinase inhibitors induced RAB45 expression and reduced mitochondrial membrane potential, resulting in inhibited colony formation of Bcr-Abl(+) progenitor cells. The overexpression of RAB45 significantly decreased colony numbers and induced apoptosis through the activation of caspases-3 and -9. Furthermore, the overexpression of RAB45 increased the phosphorylation levels of p38, resulting in the induction of apoptosis and inhibition of proliferation of CML progenitor cells. Our results identify a new signaling molecule involved in BCR-ABL modulation of apoptosis and suggest that RAB45 induction strategies may have therapeutic utility in patients with CML.

A simple method to distinguish residual elotuzumab from monoclonal paraprotein in immunofixation assays for multiple myeloma patients.

Negative immunofixation electrophoresis (IFE) of serum and/or urine is a diagnostic marker for determining a complete response (CR) after immunotherapy for multiple myeloma (MM). However, residual therapeutic antibodies such as elotuzumab (IgG-κ), can compromise IFE evaluation when the affected immunoglobulins belong to the same IgG-κ subclass. We thus sought to develop a simple and rapid method to treat patient serum before IFE to distinguish the residual elotuzumab. Serum samples from patients receiving elotuzumab were treated with a predetermined amount of soluble signaling lymphocyte activation molecule F7 (SLAMF7) protein and then subjected to conventional IFE testing. We tested our method in samples from 12 patients. The IgG-κ band in IFE disappeared or shifted after elotuzumab treatment in four patients with no bone marrow minimal residual disease and normalized free light chain, whereas seven patients with any sign of residual MM showed a remaining IgG-κ band after treatment. One-hour incubation of samples with 6-9 molar excess soluble SLAMF7 before IFE was sufficient to distinguish residual elotuzumab in 11 of 12 samples. This simple method does not require special reagents, can be performed in most clinical laboratories, and enables differentiation between patients with a CR and those requiring further treatment.

Prognostic impact of the dosage of methotrexate combined with tacrolimus for graft-versus-host disease prophylaxis after cord blood transplantation.

The optimal dosage of methotrexate (MTX) for graft-versus-host disease (GVHD) prophylaxis after cord blood transplantation (CBT) has not been well elucidated. Therefore, we conducted a retrospective study comparing a mini-MTX group (5 mg/m2 on day 1, 3 and 6) to a short-MTX group (10 mg/m2 on day 1 and 7 mg/m2 on day 3 and 6) after CBT. Sixty-three patients were classified as the mini-MTX group and 20 as the short-MTX group. The median time and cumulative incidence of neutrophil engraftment did not vary between the two groups. The cumulative incidence of grade 2-4 and grade 3-4 acute GVHD was similar in both groups. Overall survival in the mini-MTX group was significantly lower than in the short-MTX group (46.9% vs. 88.7% at 1 year, p < 0.01), contributing to higher non-relapse mortality (NRM) in the mini-MTX group (32.0% vs. 5.0% at 1 year, p = 0.02). In multivariate analysis, the mini-MTX regimen was the most powerful prognostic factor for OS (hazard ratio 4.11; p = 0.03). Although the reduced dosage of MTX had no effect on neutrophil engraftment, increased NRM due to higher incidence of infection, graft failure, and severe acute GVHD resulted in a lower survival rate in the mini-MTX group after CBT.

Expression of activated integrin ß7 in multiple myeloma patients.

Multiple myeloma (MM) is still extremely difficult to cure, and new therapeutic drugs are needed. We recently found that integrin ß7 is constitutively activated in MM cells, and chimeric antigen receptor (CAR) T cells targeting activated integrin ß7 have a significant anti-MM effect. In this study, we performed flow cytometry analysis of the expression of activated integrin ß7 in bone marrow cells from 137 symptomatic MM patients. In 60/137 (44%) MM patients, activated integrin ß7 was detected in most MM cells (> 80% of MM cells were in the positive gate). Activated integrin ß7 was highly expressed in MM cells even in heavily treated patients. It also showed high expression in many CD38lo/-CD138-CD19+B cells, which reportedly include clonotypic B cells, in the bone marrow of MM patients. Taken together, these results suggest that CAR T-cell therapy targeting activated integrin ß7 has the potential to benefit many patients with relapsed or refractory MM.