[Restructuring Torso CT Protocol for Radiation Dose Management].

PURPOSE: There are problems with dose management in X-ray computed tomography (CT) because the protocol used for any examination is not always in the same scan range. The purpose of this study was to investigate the usefulness of setting the CT protocol based on the scan range. METHODS: We evaluated the examination data of patients who underwent plain CT based on a scan range of chest to pelvis and abdomen to pelvis. The previous protocol [Chest-Abdomen Routine] was changed to the current protocols [Chest_Abdomen] and [Chest_Pelvis], and the previous protocol of [Abdomen Routine] was changed to the current protocols [Abdomen] and [Abdomen_Pelvis]. Examination data of height, scan length, volume CT dose index (CTDIvol), and dose length product (DLP) were obtained from digital imaging and communications in medicine, and radiation dose structured report using Radimetrics. The relationship between patient height and scan range, and CTDIvol and DLP was indicated in a scatter plot. Standard deviation (SD) of scan length and DLP were compared between current and previous protocols. Outliers were defined as the data exceeding average ±2SD. RESULTS: The SD of scan length decreased by 77.1% on abdomen to pelvis, and the SD of DLP decreased by 65.2% on abdomen to pelvis. The causes of the outliers were CT scan range, scan parameter, arm position, metal implants, and body thickness of patients. CONCLUSION: Setting CT protocols based on the scan range reduced SD of scan length and DLP. It was helpful for reducing the number of scan range outliers and analyzing the cause of outliers.

CT dose management of adult patients with unknown body weight using an effective diameter.

PURPOSE: To assess the usefulness of effective diameter (Deff) for CT dose management of adult patients with unknown body weight. METHODS: A total of 642 adult patients whose height and weight had been measured before CT examination (chest CT using Aquilion Prime SP, 428 patients; chest CT using Biograph mCT, 100 patients; and abdominal CT using Aquilion Prime SP, 114 patients) were retrospectively examined between April 2018 and September 2019. The Deff was automatically calculated from the lateral diameter on a CT localizer radiograph by a dose management software (Radimetrics). In order to determine the correlation between body weight and Deff, we compared volume CT dose index and dose length product between patients with body weight between 50 and 70 kg and those with Deff equivalent to body weight between 50 and 70 kg. Correlation analysis was performed by Pearson's product-moment correlation, and statistical analyses were performed by using t-test. RESULTS: The correlation coefficient values between body weight and Deff were 0.920 for chest CT using Aquilion Prime SP, 0.929 for chest CT using Biograph mCT, and 0.805 for abdominal CT using Aquilion Prime SP. In both chest and abdominal CT scans, there were no significant differences in volume CT dose index and dose length product between patients with body weight between 50 and 70 kg and those with Deff equivalent to body weight between 50 and 70 kg. CONCLUSIONS: The Deff may be useful as a somatometric parameter for CT dose management of adult patients with unknown body weight.

[Scatter Radiation Intensities during Transforaminal Lumbar Interbody Fusion Using a Mobile C-arm System].

The purpose of this study was to measure the scatter radiation intensity during transforaminal lumbar interbody fusion using a mobile C-arm system (Arcadis Orbic 3D; Siemens) and minimize radiation exposure. Dosimetry was performed with anterior-posterior and lateral continuous fluoroscopy, and cone beam computed tomography (CT). A scaffold tower (L: 300 cm×W: 200 cm×H: 150 cm) was built with radiation-resistant paper cylinders at intervals of 50 cm and plastic joints over the bed, and 100 optically stimulated luminescence dosimeters (nanoDot; Nagase Landauer) were placed on each joint. A human torso phantom from head to pelvis (Kyoto Kagaku) was positioned on the bed in a prone position. The scatter radiation dose in a lateral view was highest on the X-ray tube side at the height of 100 cm (170.5 µGy/min). The scatter radiation dose increased significantly on the X-ray tube side during lateral continuous fluoroscopy. Continuous change of surgeons' standing positions is important to minimize radiation exposure received by a specific surgeon.

Pretreatment serum soluble interleukin-2 receptor level predicts survival in patients with newly diagnosed follicular lymphoma.

This retrospective, multicenter observational study investigated the prognostic value of pretreatment serum soluble interleukin-2 receptor (sIL-2R) level for outcomes of newly diagnosed follicular lymphoma (FL) grade 1-3a who required treatment at diagnosis. A total of 628 patients were recorded, and 502 of these were eligible for analysis. Patients were divided into four quartiles, based on their serum sIL-2R levels as follows: Q1 (sIL-2R < 520 IU/mL), Q2 (520 ≤ sIL-2R < 1030 IU/mL), Q3 (1030 ≤ sIL-2R < 2530 IU/mL) and Q4 (sIL-2R ≥ 2530 IU/mL). Using a multivariable Cox proportional-hazards model, we showed the adjusted probability of overall survival (OS) decreased with increasing serum sIL-2R levels (p for trend = .007). Similar trends were observed for disease-specific survival (DSS) and progression-free survival (PFS). In conclusion, pretreatment serum sIL-2R levels significantly and dose-dependently associate with worse outcomes (OS, DSS and PFS) of patients with newly diagnosed FL.

Treatment outcomes of chronic-phase chronic myeloid leukemia with resistance and/or intolerance to a 1st-line tyrosine kinase inhibitor in Japan: the results of the New TARGET study 2nd-line.

We herein report the results of the New TARGET study 2nd-line, which collected data on patients with chronic-phase (CP) chronic myeloid leukemia (CML) who received a 2nd-line tyrosine kinase inhibitor (TKI) because of resistance and/or to a 1st-line TKI. A total of 98 patients were enrolled intolerance between April 2010 and March 2013, and 82 patients were analyzed. The median age was 54 years (range 22-88 years). Seventy-six patients (93%) received imatinib as the 1st-line TKI. Forty-five (55%) and 37 (45%) patients began nilotinib and dasatinib treatments at entry, respectively. First-line TKI treatment achieved complete hematological response in 79 patients (96%) and complete cytogenetic response (CCyR) in 49 patients (60%), respectively. Nine patients (11%) had BCR-ABL1 kinase domain point mutations at enrollment. The estimated 3-year progression-free-survival rate after enrollment was 98.7% (95% CI 91.1-99.8%). Overall, the probabilities of achieving CCyR and a major molecular response were 89.3% (95% CI 81.4-94.8%) and 87.2% (95% CI 78.1-93.8%), respectively. There were no new safety issues. This study demonstrated that CML-CP patients in Japan who are resistant and/or intolerant to a 1st-line TKI can achieve an extremely good outcome by 2nd-line TKI treatment.

Deeper molecular response is a predictive factor for treatment-free remission after imatinib discontinuation in patients with chronic phase chronic myeloid leukemia: the JALSG-STIM213 study.

The objective of this prospective clinical trial (JALSG-STIM213, UMIN000011971) was to evaluate treatment-free remission (TFR) rates after discontinuation of imatinib in chronic myeloid leukemia (CML). CML patients who received imatinib treatment for at least 3 years and sustained deep molecular response for at least 2 years were eligible. Molecular recurrence was defined as loss of major molecular response (MMR). Of the 68 eligible patients, 38.2% were women, the median age was 55.0 years, and the median duration of imatinib treatment was 97.5 months. The 12-month TFR rate was 67.6%. Patients who lost MMR were immediately treated with imatinib again; all re-achieved MMR. Three-year treatment-free survival (TFS) was estimated as 64.6% using the Kaplan-Meier method. Undetectable molecular residual disease (UMRD) was defined as no BCR-ABL1 in > 100,000 ABL1 control genes using international scale polymerase chain reaction. UMRD at the study baseline was found to be predictive of continuation of TFR. Our findings suggest that CML patients who meet all the eligibility criteria that have commonly been used in the TFR trials are able to discontinue imatinib use safely. TFR may thus be valuable as a new goal for CML treatment in Japan.

New variant of acute promyelocytic leukemia with IRF2BP2-RARA fusion.

We present an acute promyelocytic leukemia (APL) patient with two subtypes of IRF2BP2-RARA, in which the IRF2BP2 gene showed completely new breakpoints. Bone marrow examination revealed morphologic features indicative of APL. However, promyelocytic leukemia-RARA fusion was not detected. A paired-end mRNA sequencing followed by RT-PCR and direct sequencing revealed two types of fusion transcripts between exon 1B of IRF2BP2 and exon 3 of RARA. The patient received all-trans retinoic acid and conventional chemotherapy, but showed resistance. This is the second report of IRF2BP2 involvement in APL, and we describe various breakpoints for the IRF2BP2-RARA fusion gene.

A case of central nervous system relapse in acute promyelocytic leukemia.

A 70-year-old woman who have achieved complete remission (CR) of acute promyelocytic leukemia (APL) with all-trans retinoic acid and chemotherapy presented with abnormal sensation in the right lateral thigh and the bilateral legs. In addition, neurological examination revealed weakness of the left shoulder abduction, the right hand, and the bilateral lower limbs. Atypical promyelocytes were detected in the cerebrospinal fluid, in spite of normal finding in the peripheral blood smear. Magnetic resonance imaging showed gadolinium-enhanced multiple intradural/extramedullary lesions in the whole spine. Nerve conduction studies of the right limbs revealed sensorimotor conduction abnormalities, conspicuously in the posterior tibial and sural nerves. As a result, she was diagnosed as having intrathecal relapse of APL, associated with multiple mononeuropathy. The neurological symptoms were completely disappeared by intrathecal chemotherapy and whole-spine radiotherapy, suggesting that the neuropathy was possibly caused by meningeal infiltration affecting multiple spinal nerve roots. Since extramedullary or intrathecal relapse is extremely rare in APL compared with other types of leukemia, precise neurological evaluations and suitable treatment should be performed immediately, when APL patients with CR manifest some neurological symptoms.

Quantitative polymerase chain reaction analysis with allele-specific oligonucleotide primers for individual IgH VDJ regions to evaluate tumor burden in myeloma patients.

Quantitative polymerase chain reaction (PCR) with patient-specific, allele-specific oligonucleotide (ASO) primers for individual immunoglobulin H VDJ region (ASO-PCR) amplification was performed using several sources of clinical material, including mRNA from peripheral blood cells (PBMNCs), whole bone marrow cells (BMMNCs), and the CD20+ CD38- B-cell population in bone marrow, as well as cell-free DNA from the sera of patients with multiple myeloma (MM). We designed the ASO primers and produced sufficient PCR fragments to evaluate tumor burden in 20 of 30 bone marrow samples at diagnosis. Polymerase chain reaction amplification efficiency depended on primer sequences because the production of ASO-PCR fragments did not correlate with serum M-protein levels. However, the ASO-PCR levels in BMMNCs showed statistically significant correlations with those in PBMNCs and CD20+ CD38- B-cells. The good association between the BMMNC and PBMNC data indicated that PBMNCs could be a suitable source for monitoring minimal residual disease (MRD). In the case of cell-free DNA, ASO-PCR levels showed a unique pattern and remained high even after treatment. Because the sequence information for each ASO-PCR product was identical to the original, the cell-free DNA might also be useful for evaluating MRD. Moreover, the ASO-PCR products were clearly detected in 17 of 22 mRNA samples from CD20+ CD38- populations, suggesting that MM clones might exist in relatively earlier stages of B cells than in plasma cells. Thus, ASO-PCR analysis using various clinical materials is useful for detecting MRD in MM patients as well as for clarifying MM pathogenesis.

Donor cell-derived chronic myeloproliferative disease with t(7;11)(p15;p15) after cord blood transplantation in a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia.

We report a case of donor cell-derived chronic myeloproliferative disease with t(7;11)(p15;p15) occurring after cord blood transplantation (CBT). A 41-year-old man developed precursor B-cell acute lymphoblastic leukemia with a karyotype of 46, XY, t(9;22)(q34;q11) and inv(9)(p11;q13), for which he received CBT from a sex-mismatched donor at the first complete remission of the leukemia. Five months after CBT, gradual neutrophilia of unknown origin developed following the myeloid reconstitution after CBT. Karyotyping of bone marrow cells at 9 months after CBT showed 46, XX, t(7;11)(p15;p15) in 17/20 dividing cells, but neither Philadelphia chromosome (Ph) nor inv(9)(p11;q13) was present. This is the first report of chronic myeloproliferative disease with t(7;11)(p15;p15) that developed in donor cells after CBT. The donor was well-developed and healthy, at least at the time of follow-up, half a year after the birth.

Donor Cell-Derived Chronic Myeloproliferative Disease with t(7;11)(p15;p15) after Cord Blood Transplantation in a Patient with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia.

We report a case of donor cell-derived chronic myeloproliferative disease with t(7;11)(p15;p15) occurring after cord blood transplantation (CBT). A 41-year-old man developed precursor B-cell acute lymphoblastic leukemia with a karyotype of 46, XY, t(9;22)(q34;q11) and inv(9)(p11;q13), for which he received CBT from a sex-mismatched donor at the first complete remission of the leukemia. Five months after CBT, gradual neutrophilia of unknown origin developed following the myeloid reconstitution after CBT. Karyotyping of bone marrow cells at 9 months after CBT showed 46,XX, t(7;11)(p15;p15) in 17/20 dividing cells, but neither Philadelphia chromosome (Ph) nor inv(9)(p11;q13) was present. This is the first report of chronic myeloproliferative disease with t(7;11)(p15;p15) that developed in donor cells after CBT. The donor was well-developed and healthy, at least at the time of follow-up, half a year after the birth.

A novel chromosomal abnormality, t(6;10)(q27;q22), found in a polycythemic potential donor for allogeneic hematopoietic stem cell transplantation.

A 59-year-old man was a potential donor for allogeneic hematopoietic stem cell transplantation and was found to be healthy but slightly polycythemic. The bone marrow was morphologically normal, but karyotyping of bone marrow cells showed t(6;10)(q27;q22) in 7 of 20 metaphases analyzed by G-banding and only the t(6;10) abnormality in 3 of 5 metaphases analyzed by the spectral karyotyping method. G-banding analysis of peripheral blood mononuclear cells cultured with phytohemagglutinin for 72 hours showed a normal karyotype in all 20 metaphases analyzed.These findings suggest clonal expansion with t(6;10)(q27;q22) in the bone marrow of this individual. He was determined to be ineligible for donation. A coordinated nationwide work-up for older donors is necessary to ensure high-quality standards.

Analysis of sepsis in allogeneic bone marrow transplant recipients: a single-center study.

We reviewed the records of 235 consecutive recipients of allogeneic bone marrow transplantation (allo-BMT) at our center between February 1983 and October 2000. Sepsis occurred in 25 patients (10.6%) at a median of 10 days (range, 1-280 days) after BMT. Five of the 25 patients (20%) died of sepsis. Pathogens isolated from blood culture were gram-positive cocci in 19 patients, gram-negative rods in 7, fungi in 2, and others in 1 patient. Two pathogens were detected concomitantly in 4 patients. Univariate analysis revealed that risk factors for sepsis were selective gut decontamination using lomefloxacin hydrochloride and nystatin, an unrelated donor, HLA mismatched BMT, and stomatitis. Multivariate logistic regression analysis revealed that an unrelated donor was the only significant independent risk factor, with a relative risk of 5.432. In 12 of 25 patients with sepsis, the pathogens of sepsis were sensitive to antibiotics used for gut decontamination. Selective gut decontamination significantly increased the incidence of sepsis, especially that with gram-positive cocci, but not the mortality rate of sepsis, compared with total gut decontamination using vancomycin. We also found a significant relationship between pathogens isolated from blood culture and those isolated from surveillance cultures of stool, urine, and gargled water in the period before sepsis occurred. The present study revealed an independent risk factor for sepsis (unrelated donor), the feasibility of selective gut decontamination, and the importance of surveillance culture.