[Durable remission attained by long-term brentuximab vedotin administration in a relapsed post-allogeneic bone marrow transplant Hodgkin lymphoma patient].

The prognosis for relapsed Hodgkin lymphoma after allogeneic hematopoietic cell transplantation (HSCT) is poor, partly because of limited treatment options. Here we present a case of a Hodgkin lymphoma patient who relapsed after allogeneic HSCT but remains in complete remission (CR) at 38 months from the start of extended brentuximab vedotin (BV) dosing. A 33-year-old man with refractory and relapsed nodular sclerosis classical Hodgkin lymphoma who underwent previous treatments, including adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) ; seven combination regimens; and autologous HSCT, prior to allogeneic HSCT achieved CR after three cycles of BV. BV was continued for 26 cycles and then discontinued because of a neurogenic bladder. The other adverse effects were mild paresthesia in the fingers, mild dysgeusia, and fatigue. The patient still remains in CR at 38 months from the start of BV. Thus, extended BV dosing may be a treatment option for relapsed and refractory Hodgkin lymphoma after allogeneic HSCT.

Mantle cell lymphoma presenting with spontaneous splenic rupture.

A 48-year-old man was transferred to our emergency room because of sudden-onset epigastric pain and nausea. Abdominal contrast-enhanced computed tomography (CT) showed splenomegaly with splenic infarction and intra-abdominal bleeding, suggestive of splenic rupture. An emergent open splenectomy was performed. His spleen was markedly swollen and showed continuous bleeding due to a laceration. On histopathological examination, his spleen was filled with abnormal tumor cells. He was diagnosed as having mantle cell lymphoma based on the findings of immunohistochemical and cytogenetic analyses of the spleen. Mantle cell lymphoma cells were identified in the bone marrow and ileum, and he was determined to be in stageIVA by positron emission tomography (PET)-CT. He was administered rituximab combined with hyper-CVAD/MA chemotherapy (R-hyper-CVAD/MA regimen). After two courses of the R-hyper-CVAD/MA regimen, he achieved complete response, as confirmed by PET-CT. He received four courses in total of the R-hyper-CVAD/MA regimen, followed sequentially by high-dose chemotherapy and autologous peripheral blood stem cell transplantation (auto-PBSCT). He is currently alive and free of disease. This is the 10(th) report of a mantle cell lymphoma case with spontaneous splenic rupture. We herein review previous reports and emphasize the importance of awareness of hematological malignancies when encountering a case with spontaneous splenic rupture.

Data analysis of average glandular dose in mammography toward revision of the diagnostic reference level of Japan.

Diagnostic reference level (DRL) for mammography for 2015 and 2020 has been published by J-RIME. More new dose studies are needed to revise the next DRL. In preparation for the next revision of the DRL for mammography, this study investigated data from the Japan Central Organization on Quality Assurance of Breast Cancer Screening on the mean average glandular dose (AGD) for institutional image accreditation in 2019-2023 and the relationship between the average at eligible institutions to date and the type of breast X-ray system. The 95th percentile values of the AGD distributions for the Computed Radiography (CR) and Flat Panel Detector (FPD) systems were 2.5 mGy and 2.0 mGy, respectively. Moreover, it is assumed that AGD is decreasing due to the spread of FPD systems, and it is expected that the further spread of FPD systems and systems with W/Rh target/filter will reduce AGD in future.

Monte carlo simulation study on the dose and dose-averaged linear energy transfer distributions in carbon ion radiotherapy.

Dose-averaged linear energy transfer (LETd) is conventionally evaluated from the relative biological effectiveness (RBE)-LETd fitted function used in the treatment planning system. In this study, we calculated the physical doses and their linear energy transfer (LET) distributions for patterns of typical CIRT beams using Monte Carlo (MC) simulation. The LETd was then deduced from the MC simulation and compared with that obtained from the conventional method. The two types of LETd agreed well with each other, except around the distal end of the spread-out Bragg peak. Furthermore, an MC simulation was conducted with the material composition of water and realistic materials. The profiles of physical dose and LETd were in good agreement for both techniques. These results indicate that the previous studies to analyze the minimum LETd in CIRT cases are valid for practical situations, and the material composition conversion to water little affects the dose distribution in the irradiation field.

Flow cytometric analysis of CD34+ CD38- cells; cell frequency and immunophenotype based on CD45RA expression pattern.

INTRODUCTION: The CD34+ CD38- population in bone marrow includes hematopoietic stem/progenitor cells. Recently, in acute myeloid leukemia, the focus has shifted to flow cytometry analysis targeting CD34+ CD38- leukemic cells due to their effectiveness in minimal/measurable residual disease detection and prognosis prediction. Nevertheless, the immunophenotype and cell frequency of these cells in the bone marrow, in the absence of leukemic cells, remains unknown. We aimed to evaluate detailed characteristics of CD34+ CD38- cells in both normal and leukemic cells by flow cytometry. METHODS: We compared the cell frequency and immunophenotype of the CD34+ CD38- fraction in the following groups: patients with idiopathic thrombocytopenic purpura and malignant lymphoma as controls (n = 17), post-treatment patients without abnormal blasts (n = 35), and patients with myeloid malignancies (n = 86). The comparison was based on the presence or absence of CD45RA expression, a marker commonly used to prospectively isolate lymphoid-primed cell populations within the CD34+ CD38- fraction. RESULTS: The CD34+ CD38- CD45RA+ cell population exhibited a significant expansion in bone marrow without leukemic cells 1 month after cord blood transplantation and in various type of myeloid malignancies, compared to the control group (p < 0.01). Continuous CD45RA expression and notable expansion of the CD34+ CD38- CD45RA- population were exclusively observed in myelodysplastic syndrome-related diseases. The CD34+ CD38- CD45RA+ population displayed frequent expression of various markers in both leukemic and non-leukemic cells, in contrast to the CD34+ CD38- CD45RA- population. CONCLUSIONS: The CD34+ CD38- fraction should be carefully evaluated considering the nature of normal hematopoietic precursor cells, their cell frequency and immunophenotype, including CD45RA expression pattern, for improving the accuracy of myeloid malignancy diagnosis.

In Vivo Dosimetry in the Urethra During Prostate Carbon Ion Radiotherapy.

BACKGROUND/AIM: In vivo dosimetry can prevent dose delivery errors by directly measuring the dose of radiation administered to a patient. However, a method for in vivo dosimetry during carbon ion radiotherapy (CIRT) has not been established. Therefore, we investigated data from in vivo dosimetry of the urethra during CIRT for prostate cancer using small spherical diode dosimeters (SSDDs). PATIENTS AND METHODS: This study included five patients enrolled in a clinical trial (jRCT identifier: jRCTs032190180) on which the use of four-fraction CIRT for prostate cancer was examined. The urethral dose during CIRT for prostate cancer was measured using the SSDDs inserted into the ureteral catheter. The relative error between the in vivo and calculated doses obtained using the Xio-N treatment planning system was determined. Additionally, a dose-response stability test for the in vivo dosimeter was performed under clinical conditions. RESULTS: The relative error between the in vivo and calculated urethral doses ranged from 6 to 12%. The dose-response stability under clinical conditions of the measured dose was ≤1%. Therefore, an error >1% would be due to an interfractional patient setup error in the large dose gradient in the urethra. CONCLUSION: The usefulness of in vivo dosimetry using SSDDs in CIRT and SSDDs' potential for detecting dose delivery errors during CIRT is herein highlighted.

Successful Treatment of Warm Autoimmune Hemolytic Anemia with a Positive Donath-Landsteiner Test Using Rituximab.

Paroxysmal cold hemoglobinuria (PCH) is a rare disease in adults, and its concurrent presentation with warm-type autoimmune hemolytic anemia (AIHA) has not yet been reported. We encountered a 19-year-old woman with AIHA and a positive Donath-Landsteiner test result identified by a hemolytic attack during blood transfusion. She also showed positive results for the direct Coombs and Donath-Landsteiner antibody tests. After treatment with prednisolone followed by rituximab, the AIHA improved, and the Donath-Landsteiner antibody test result turned negative. Clinicians should be aware that patients may present with concurrent warm-type AIHA and PCH and consider rituximab for its treatment.

Relationship between electron density and effective densities of body tissues for stopping, scattering, and nuclear interactions of proton and ion beams.

PURPOSE: In treatment planning of charged-particle radiotherapy, patient heterogeneity is conventionally modeled as variable-density water converted from CT images to best reproduce the stopping power, which may lead to inaccuracies in the handling of multiple scattering and nuclear interactions. Although similar conversions can be defined for these individual interactions, they would be valid only for specific CT systems and would require additional tasks for clinical application. This study aims to improve the practicality of the interaction-specific heterogeneity correction. METHODS: The authors calculated the electron densities and effective densities for stopping power, multiple scattering, and nuclear interactions of protons and ions, using the standard elemental-composition data for body tissues to construct the invariant conversion functions. The authors also simulated a proton beam in a lung-like geometry and a carbon-ion beam in a prostate-like geometry to demonstrate the procedure and the effects of the interaction-specific heterogeneity correction. RESULTS: Strong correlations were observed between the electron density and the respective effective densities, with which the authors formulated polyline conversion functions. Their effects amounted to 10% differences in multiple-scattering angle and nuclear interaction mean free path for bones compared to those in the conventional heterogeneity correction. Although their realistic effect on patient dose distributions would be generally small, it could be at the level of a few percent when a carbon-ion beam traverses a large bone. CONCLUSIONS: The present conversion functions are invariant and may be incorporated in treatment planning systems with a common function relating CT number to electron density. This will enable improved beam dose calculation while minimizing initial setup and quality management of the user's specific system.

Development of the DICOM-based Monte Carlo dose reconstruction system for a retrospective study on the secondary cancer risk in carbon ion radiotherapy.

Objective.A retrospective study on secondary cancer risk on carbon ion radiotherapy (CIRT) is ongoing at the Heavy Ion Medical Accelerator in Chiba (HIMAC). The reconstruction of the whole-body patient dose distribution is the key issue in the study because dose distribution only around the planning target volume was evaluated in the treatment planning system.Approach.We therefore developed a new dose reconstruction system based on the Particle and Heavy Ion Transport code System (PHITS) coupled with the treatment plan DICOM data set by extending the functionalities of RadioTherapy package based on PHITS (RT-PHITS). In the system, the geometry of patient-specific beam devices such as the range shifter, range compensator, and collimators as well as the individual patient's body are automatically reconstructed. Various functions useful for retrospective analysis on the CIRT are implemented in the system, such as those for separately deducing dose contributions from different secondary particles and their origins.Main results.The accuracy of the developed system was validated by comparing the dose distribution to the experimental data measured in a water tank and using a treatment plan on an anthropomorphic phantom.Significance.The extended RT-PHITS will be used in epidemiological studies based on clinical data from HIMAC.

VS38 staining contributes to a novel gating strategy in flow cytometry for small B cell lymphoma, especially in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia.

BACKGROUND: Multi-parametric flow cytometry (MFC) is a helpful tool for detecting neoplastic cells in malignant lymphoma; however, lymphoma cells can be difficult to detect when characteristic immunophenotypic abnormalities are not evident. We evaluated the stainability of VS38, which is used for multiple myeloma, in normal and abnormal B cells using MFC to develop a new strategy for detecting lymphoma cells. METHODS: We compared the median fluorescence intensity of VS38 staining in lymphocytes from patients without hematopoietic neoplasms and in B cells from 26 patients with B cell lymphoma (BCL). To evaluate the performance of VS38 gating, we compared VS38-positive B cells with the percentages of BCL cells, and with the mutation ratios of MYD88 L265P measured by droplet digital PCR in patients with lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinemia (WM). RESULTS: CD27-positive memory B cells were stained with VS38, whereas normal lymphocytes were faintly stained. Lymphoma cells were stained with VS38 in 11 of 12 patients with LPL/WM, 3 of 3 with chronic lymphocytic leukemia, 3 of 5 with mantle cell lymphoma, 2 of 4 with follicular lymphoma, and 1 of 1 with splenic marginal zone lymphoma. The percentages of VS38-positive B cells in VS38-positive BCL were equivalent to those of lymphoma cells and the mutation ratios of MYD88 L265P in LPL/WM. CONCLUSIONS: VS38 identified neoplastic cells in plasma cell disorders and BCL. This might improve the accuracy of BCL diagnosis, especially in patients with LPL/WM.

Evaluation of the Correction Methods Using Age and BMI for Estimating CT Organ Dose Using a Radiophotoluminescence Glass Dosimeter and a Monte Carlo-based Dose Calculator.

ABSTRACT: The size-specific dose estimates (SSDE) have been recommended to replace the volume computed tomography dose index (CTDIvol) because it takes patient size into account. On the other hand, organ dose is thought to be a more appropriate quantity in the radiation protection field due to its correlation with radiation risk. The web-based computed tomography (CT) dose calculator WAZA-ARIv2 only offers organ doses for adults with four different body shapes and for children with five different ages. Since the American Association of Physicists in Medicine (AAPM) offers the conversion factors for SSDE and the correlation of SSDE with organ dose has been demonstrated, implementation of the conversion table might improve the accuracy of WAZA-ARIv2. This study aimed to evaluate a body mass index (BMI)-based and age-based correction method for estimation of the organ dose by using a radiophotoluminescence dosimeter (RGD), an anthropomorphic phantom, and the dose calculator WAZA-ARIv2. RGDs were individually calibrated by using an ISOVOLT TITAN-320 x-ray generator. The ratio of the SSDE conversion factors (CFSSDE) was used as the comparison index. For the BMI-based correction method, the ratio of CFSSDE values for the adult phantoms was expected to be 1.065, and the average ratio of the organ doses for the adult phantoms was 1.163 ± 0.169. For the age-based correction method, the ratio of CFSSDE value for 5- and 10-y-old pediatric phantoms was expected to be 0.889, and the ratios of the organ doses were 0.866 ± 0.024 and 0.909 ± 0.047 for the WAZA-ARIv2 dosimetry system and RGD dosimetry system, respectively. In conclusion, both evaluations of the experimental results showed the consistency between WAZA-ARIv2 and the SSDE conversion factor table. Moreover, the importance of taking the measurement position into account when applying the mass attenuation coefficient was demonstrated according to this study.

Evaluation of Organ Doses for Pediatric Computed Tomography Using a Newly Designed Radiophotoluminescence Glass Dosimeter and Comparison with a Monte Carlo Simulation-based Dose Calculator.

ABSTRACT: Management of patient dose is an effective way to help optimize computed tomography (CT) scanning conditions and CT dose. Organ dose is one of the preferred quantities for radiation protection because of its correlation with radiation risk. To date, the WAZA-ARI dose calculator is the only freely available CT dose calculator also applicable for pediatric patients. However, no reports of its evaluation have appeared since the latest version of WAZA-ARI was released. In this study, to evaluate the latest version of WAZA-ARI, we measured the organ dose in a 5-y-old anthropomorphic phantom by a newly developed radiophotoluminescence glass dosimeter (RGD) dosimetry system and compared these results with the calculation results from WAZA-ARI. The newly designed RGDs have less angular dependence because of the additional filter. RGDs were individually calibrated with the ISOVOLT TITAN-320 x-ray generator. All the experimental measurements for this study were performed using a CT scanner. To consider the difference of CT output between the nominal and actual machine, the measured CTDIair was used to correct the calculation results obtained from WAZA-ARI. After the corrections using the measured CTDIair, the calculation results from WAZA-ARI were relatively lower than the measured results with a range of 8-20%, which corresponds to the dose difference caused by the difference in effective diameter. In conclusion, the calculation accuracy of WAZA-ARI is guaranteed when the normalization factor specific to each CT scanner (CTDIair) and the shape of the phantom are taken into consideration.

Technical Note: validation of a material assignment method for a retrospective study of carbon-ion radiotherapy using Monte Carlo simulation.

We propose a two-step method to converse human tissue materials from patient computed tomography (CT) images, which is required in dose reconstructions for a retrospective study of carbon-ion radiotherapy (CIRT) using Monte Carlo (MC) simulation. The first step was to assign the standard tissues of the International Commission on Radiological Protection reference phantoms according to the CT-number. The second step was to determine the mass density of each material based on the relationship between CT-number and stopping power ratio (Hounsfield unit [HU]-SPR) registered in treatment planning system (TPS). Direct implementation of the well-calibrated HU-SPR curve allows the reproduction of previous clinical treatments recorded in TPS without uncertainty due to a mismatch of the CT scanner or scanning conditions, whereas MC simulation with realistic human tissue materials can fulfill the out-of-field dose, which was missing in the record. To validate our proposed method, depth-dose distributions in the homogenous and heterogeneous phantoms irradiated by a 400 MeV/u carbon beam with an 8 cm spread-out Bragg peak (SOBP) were computed by the MC simulation in combination with the proposed methods and compared with those of TPS. Good agreement of the depth-dose distributions between the TPS and MC simulation (within a 1% discrepancy in range) was obtained for different materials. In contrast, fluence distributions of secondary particles revealed the necessity of MC simulation using realistic human tissue. The proposed material assignment method will be used for a retrospective study using previous clinical data of CIRT at the National Institute of Radiological Sciences (NIRS).

Development and characterization of optical readout well-type glass gas electron multiplier for dose imaging in clinical carbon beams.

The use of carbon ion beams in cancer therapy (also known as hadron therapy) is steadily growing worldwide; therefore, the demand for more efficient dosimetry systems is also increasing because daily quality assurance (QA) measurements of hadron radiotherapy is one of the most complex and time consuming tasks. The aim of this study is to develop a two-dimensional dosimetry system that offers high spatial resolution, a large field of view, quick data response, and a linear dose-response relationship. We demonstrate the dose imaging performance of a novel digital dose imager using carbon ion beams for hadron therapy. The dose imager is based on a newly-developed gaseous detector, a well-type glass gas electron multiplier. The imager is successfully operated in a hadron therapy facility with clinical intensity beams for radiotherapy. It features a high spatial resolution of less than 1 mm and an almost linear dose-response relationship with no saturation and very low linear-energy-transfer dependence. Experimental results show that the dose imager has the potential to improve dosimetry accuracy for daily QA.

cDNA-Based Mutation Screening Using a Combination of High-Resolution Melting Curve and Fragment Analysis Facilitates Efficient CCR4 Mutation Analysis in Adult T-Cell Leukemia/Lymphoma.

OBJECTIVES: C-C chemokine receptor type 4 (CCR4) proteins are expressed on the neoplastic cells of adult T-cell leukemia/lymphoma (ATLL). As the mutation status of CCR4 gene is reported to correlate with significant clinical information such as prognosis and response to mogamulizumab, we aimed to establish a screening method that is suitable for clinical laboratory tests. METHODS: In 34 patients with ATLL, CCR4 mutation analysis, high-resolution melting (HRM) analysis, fragment analysis, and direct sequencing were performed using both genomic DNA and complementary DNA (cDNA). Furthermore, 38 cases of asymptomatic carriers of human T-cell leukemia virus type 1 (HTLV-1) were screened for CCR4 mutation. RESULTS: Mutation analysis by direct sequencing of 34 ATLL clinical samples detected CCR4 mutation in four genomic DNA samples and seven cDNA samples, and two novel mutations were identified. All CCR4 mutations detected by direct sequencing were positive for HRM analysis and/or fragment analysis. CCR4 mutation was not detected in the asymptomatic carriers of HTLV-1. CONCLUSIONS: CCR4 mutation screening by a combination of HRM and fragment analysis using cDNA is a simple and practical method, and it will contribute to better decision making for a therapeutic strategy, providing a rapid CCR4 mutational status to clinicians.

Evaluation of SF3B1 Mutation Screening by High-Resolution Melting Analysis and its Clinical Utility for Myelodysplastic Syndrome with Ring Sideroblasts at the Point of Diagnosis.

BACKGROUND: SF3B1 (splicing factor 3B subunit-1) somatic mutation is specifically detected in myelodysplastic syndrome (MDS) with ring sideroblasts (MDS-RS). We investigated the sensitivity and utility of SF3B1 mutation analysis as a clinical laboratory test. METHOD: Detection limit for SF3B1 mutations by high-resolution melting (HRM) analysis was investigated by plasmid mixture. In 67 MDS patients, we examined the association between SF3B1 mutation and prognostic evaluation using the Revised International Prognostic Scoring System and revalidated MDS classifications based on the revised 4th edition of the WHO classification. RESULTS: HRM analysis enabled mutation detection in the 12.5% SF3B1 mutant alleles. SF3B1 mutation was detected in 9 cases, mostly in the low-risk group. Cases of MDS with ring sideroblasts unrelated to SF3B1 mutation were detected in the high-risk group. Two cases were reclassified as MDS-RS after detecting SF3B1 mutation. CONCLUSIONS: SF3B1 mutation analysis as an initial screening at diagnosis increases the accuracy of prognostic prediction and disease classification.