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  • American Society of Hematology  (11)
  • 1
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    Reversal of Renal Function and Its Prognostic Impact in Patients with Multiple Myeloma in the Era of Novel Agents
    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 3056-3056
    Details
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 3056-3056
    Abstract: Aim and Background: Renal impairment (RI) is common feature in patients with multiple myeloma (MM) and is considered as a poor prognostic factor. Improvement of renal function can lead to the improved survival in patients with MM, however little is known on the prognostic impact of reversal of RI compared to that of the patients without RI at diagnosis in the novel agent era. To address this issue, we retrospectively analyzed the impact of RI on survival of newly diagnosed multiple myeloma (NDMM) patients with or without RI seen at our Department over the past 15 years. Patients and Methods: The study population included all patients diagnosed as MM and treated during May 2000 to March 2015 at Kameda Medical Center, Kamogawa-shi, Japan. We reviewed and retrospectively analyzed the medical records of the Department of Hematology/Oncology. All statistical analyses were performed with EZR, which is a graphical user interface for R ver. 3.2.1. Results: We identified 258 patients with NDMM during this period. RI was defined as eGFR 〈 50ml/min/1.73m2. The median age of patients at diagnosis was 72 years (range 42-90), and 144 patients (55.6%) were male. The median follow-up period for the entire group was 37 months, median serum creatinine at diagnosis was 2.01mg/dL (range 0.4-15) and median eGFR was 52.4ml/min/1.73m2 (range: 2.11-136). RI was observed 122 patients (47.2%). Median serum creatinine of patients with and without RI at diagnosis was 2.07 mg/dL (range: 0.80-4.2) and 0.75mg/mL (range: 0.4-1.1), respectively (p 〈 0.001). Patients with RI had significantly higher proportion of light-chain only disease (39.3% vs 12.5%, p 〈 0.001), International Staging System (ISS) stage 3 (76.2%, vs 31.6%, p=0.001), and lower hemoglobin concentration (Hb 〈 8.5mg/dL: 44.2% vs 21.3%, p 〈 0.001). Bortezomib use, high risk cytogenetics, sex, serum LDH, age at diagnosis, amount of involved immunoglobulin, light chain subtype, and urine albumin at diagnosis were not different between patients with and without RI. Median overall survival (OS) for patients with (n=122) and without (n= 136) RI were 39 months and 57 months, respectively (p=0.16). The median OS for patients with or without RI before and after December 2006, when bortezomib became available in Japan, were 28 months and 41 months (p= 0.66), and 46 months and 71 months (p=0.01), respectively. To evaluate the prognostic impact of renal improvement on survival, patients were divided into 3 groups according to the eGFR and subsequent renal response: Group A; eGFR ≥ 50ml/min/1.73m2 at diagnosis, Group B; eGFR 〈 50 ml/min/1.73m2 at diagnosis but improved to 〉 50ml/min/1.73m2, Group C; eGFR 〈 50 ml/min/1.73m2 at diagnosis, and remained 〈 50 ml/min/1.73m2. Median OS of patients with Group A, B, and C was 57 months (n=136), 41 months (n=73), and 25 months (n=49), respectively (p=0.02) (Figure 1). When patients were analysed before and after 2006, the median OS of patients with group A, B, and C before 2006 were 41months (n=59), 38months (n=25) and 19months (n=15) (p=0.02), and those of after 2006 were 71 months (n=77), 46 months (n=48) and not reached (n=34) (p=0.03), respectively. On landmark analysis, median OS at 6 months in each group (Group A, B, and C) were 66 months (n=122), 43 months (n=42), 62 months (n=54), respectively (p= 0.74). Early mortality rate (within 6 months from diagnosis) was significantly higher in patients with group C (16%) compared to other groups (8.5% for group A and 8% for group B, respectively, p=0.03). Patients with group C has significantly higher proportion of mortality rate of infectious disease (26.9%) compared to other groups (7.6% for group A and 11.5% for group B, respectively, p=0.04). Reversal of RI was associated with free light chain (FLC) reduction rate 〉 95% at day 21, age 〈 70years, and treatment response ≥VGPR on univariate analysis, but only FLC reduction rate 〉 95% at day 21 retained its significance on multivariate analysis Conclusions: Patients with MM with RI showed poor prognosis compared to those without RI. FLC reduction 〉 95% at day 21 was the independent prognostic predictor for reversal of RI. The higher mortality rate within 6 month of diagnosis observed in patients with RI without renal recovery might attribute to the inferior survival in patients with RI. Although patients with RI with improved renal function had superior survival compared to those without, it remains inferior to the patients without RI at diagnosis Figure 1. mOS of group A, B, and C Figure 1. mOS of group A, B, and C Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V126.23.3056.3056
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 2
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    Prognostic Impact of Immunophenotypic Response and Normalization of Serum Free Light Chain Among Patients with Multiple Myeloma
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 2116-2116
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 2116-2116
    Abstract: Introduction: With the development of novel therapeutic agents, more than 30% of patients with multiple myeloma (MM) achieve complete response (CR) as defined by the International Myeloma Working Group (IMWG). However, most patients that achieve CR ultimately die due to relapse, suggesting the presence of minimal residual disease (MRD) in these patients. Multicolor flow cytometry (MFC) allows the detection of 〈  10-4 clonal plasma cells in normal bone marrow cells and has been used for detecting MRD after treatment. MFC-defined immunophenotypic response (IR) has emerged as a more relevant prognostic factor in patients with MM. However, the relevance of the prognostic impact of IR and the normalization of serum free light chain (sFLC) ratio remain unclear. We retrospectively analyzed the impact of IR, conventional immunofixation negative CR (CR), and CR plus FLC kappa/lambda (k/l) normal CR (sCR) on the prognosis of 83 patients with MM who obtained better than very good partial response (VGPR) at Kameda Medical Center, Kamogawa, Japan. Methods: Among the 164 patients treated at our hospital between April 2005 and July 2014, 83 patients that achieved more than VGPR were included in this study. The study population consisted of 49 males and 34 females with a median age of 71 years. All patients received at least one course of novel agent-containing therapeutic regimen. Autologous stem cell transplantation was performed 43 patients. Maintenance treatment was not systematically given, but patients failed to achieve CR continued to receive treatment until CR was obtained. Treatment responses were assessed using the IMWG criteria, and the best response to treatment during the course of disease was assessed by simultaneous analysis by serum immunofixation, sFLC measurements, and MFC analysis of bone marrow plasma cells. Identification of plasma cells MFC requires at least two markers (CD38 and either CD45 or CD138) by single-tube 6-color flow-cytometry. Neoplastic plasma cells were further identified from normal plasma cell based on differential expression of CD19 and CD45 characteristics. Patients were considered MRD negative (IR) when ≤ 50 neoplastic plasma cells were detected by MFC in the bone marrow samples at the sensitivity limit of 10-4. Overall survival (OS) and Time to next treatment (TNT) differences between curves were calculated by two-sided log-rank test. Subjects were classified into three categories, i.e., CR with MRD positive or negative and VGPR, and TNT and OS were compared between groups. Results: At a median follow-up of 44.8 months, 83 patients obtained better than VGPR, ie; CR, 55 patients, VGPR, 28 patients. Among the 55 patients who obtained CR, normalization of sFLC k/l and IR were achieved in 48 (88%) and 28 (51%) patients, respectively. Conversely, normal sFLC k/l ratio was achieved in 66 patients, 50 were in CR and 16 were in VGPR. IR was obtained in 34/83 (41%) patients. Among 48 CR patients with normal sFLC k/l (stringent CR), IR was obtained 27 patients (56%). All of the 7 CR patients with abnormal sFLC k/l (non-stringent CR) did not achieve IR. Kaplan–Meier estimated 3- and 5-year OS were 94% and 80% in patients with CR, 90% and 71% in patients with VGPR. No significant differences were observed at 3- and 5-year OS between patients achieved CR and VGPR. Among the patients with VGPR or better response, patients with IR showed significantly longer TNT compared to those without IR. However, The patients who achieved CR and IR showed significantly longer TNT compared to those with VGPR (P=0.004), but CR patients without IR showed similar TNT curve with VGPR patients. Patients with both CR and IR showed longer TNT than those CR but without IR, although difference between the 2 groups was marginally significant (P=0.06). Although, patients with IR and normal sFLC showed significantly longer TNT compared to those with VGPR, it was not translated to longer OS reflecting the continuous maintenance treatment for VGPR patients. Conclusion: Although both achievement of CR, normalization of sFLC k/l, and IR appeared to confer on longer TNT and OS, obtaining IR seems to have greater implications for longer survival compared to CR or FLC k/l normalization. MFC analysis is a rapid, affordable, and easy performable method for measurement of MRD, and IR could be considered as a goal of treatment for patients with MM. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.2116.2116
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
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  • 3
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    Clinical Features of and Treatment Outcome of Neurolymphomatosis: Single Institutional Experience over 7 Years
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 1717-1717
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 1717-1717
    Abstract: Introduction: Neurolymphomatosis (NL) is an extremely rare neurological manifestation of non-Hodgkin lymphoma (NHL) in which peripheral nerve infiltration of lymphoma cells is a dominant feature both clinically and pathologically. Previously, we reported a high frequency of NL as a relapse disease of intravascular large B cell lymphoma (IVL), although NL could present as an initial disease as well as relapsed disease in other types of NHL. In addition, the clinical features and treatment outcomes of NL are largely unknown. However, the recent increase in use of PET/CT in lymphoma has facilitated the diagnosis of NL. Here, we report our experience with NL at our hospital over the period from January 2006 to July 2014. Methods: We reviewed the clinical records at the Hematology/Oncology Department of Kameda Medical Center. The diagnosis of NL required: 1) clinical symptoms and neurological examination findings related to the cranial or spinal nerves; and 2) histological confirmation of malignant lymphoma cells within the peripheral nerve, nerve root/plexus, or cranial nerve; or 3) CT/MRI demonstration of nerve enhancement and/or enlargement of peripheral nerve(s) or nerve root that were also demonstrated by the accumulation of FDG by FDG-PET/CT. Patients with stomach limited mucosa-associated lymphoid tissue (MALT) lymphoma and leukemic infiltration of peripheral nerve due to acute leukemia were excluded from the study. Results: Over the past 7 years, there were 514 patients diagnosed with NHL. Among them, we identified 9 patients (1.8%) diagnosed as having NL. The patients consisted of 2 men and 7 women with a median age of 72 years (range: 63 – 83 years). All 9 patients were histologically diagnosed as a diffuse large B-cell lymphoma (DLBCL). NL occurred as part of the presenting disease in 3 patients and as a relapse disease in the remaining 6 patients. 4 NL patients presented as a relapse disease of IVL, 2 as a relapse disease of nodal DLBCL, and 3 as a concomitant extranodal DLBCL (stomach, ileum, and uterus). CD5 was positive in 7 cases (78%). Diagnosis of NL was made by neurological findings, enlargement and enhancement of affected cranial or peripheral nerves by MRI, and FDG-uptake of affected nerve demonstrated by PET/CT in all patients. Autopsy also confirmed the lymphoma infiltration in 1 patient. The affected nerves included the lumbosacral nerve (5 patients), brachial plexus (2 patients), peroneal nerve (1 patients), cranial nerves (4 patients), especially oculomotor nerve (2 patients), trigeminal nerve (2 patients). Cerebrospinal fluid cytology was positive in 4 cases (44%). All 9 patients received a treatment regimen including high-dose methotrexate (MTX) in addition to rituximab containing systemic chemotherapy. Six patients received involved nerve irradiation, 4 patients at relapse and 2 at presentation. Neurological symptoms of the all patients responded promptly. Six patients subsequently developed CNS involvement despite the prophylactic use of high-does MTX. Six patients died due to progressive NL with a median of 11.3 months after NL development. Three patients are still alive 8, 9, and 92 months from the diagnosis. Two patients received autologous stem cell transplantation (auto-SCT), one survived for more than 7 years but the other relapsed 4 months after auto-SCT and being treated with radiation and chemotherapy. Conclusions: NL occurs in a minority of patients (1.8%) and can present in diverse ways, both at initial diagnosis of lymphoma or after treatment. All of them were DLBCL and 78% were CD5-positive. IVL is a most common type of lymphoma subtype in which develop NL. Contemporary imaging techniques including MRI and PET/CT, can often detect relevant neural involvement. Prognosis remains poor once patient developed NL despite the use of high-dose MTX and rituximab containing aggressive chemotherapy included auto-SCT. Only involved nerve irradiation was effective for the relief of neurologic symptoms. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.1717.1717
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
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  • 4
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    Clinical and Prognostic Significance of Bone Marrow Imaging of Appendicular Skeletons By Low-Dose Multi-Detector Computed Tomography in Patients with Aplastic Anemia and Myelodysplastic Syndorme
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 5602-5602
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 5602-5602
    Abstract: Background: Myelodysplastic syndrome (MDS) and aplastic anemia (AA) comprise a heterogeneous group of bone marrow failure disorders. As both show profound hypocellular marrow with minimal morphological atypia, differentiation of MDS and AA is often difficult by bone marrow and laboratory examination alone. Red to yellow marrow conversion occurs with age in the appendicular skeleton (AS), where red marrow is converted to yellow marrow until the early 20s. Although an abnormal distribution of red marrow in AS has previously been reported in small numbers of patients with MDS, along with leukemia and lymphoma by MRI, there have been no further reports to date. Here, we examined the distribution of red marrow in AS by low-dose multi-detector CT (MDCT) in AA and MDS. We analyzed the relationships between the abnormal medullary pattern in AS and laboratory variables, subsequent development of leukemic transformation, and survival in MDS patients. Patients: We performed low-dose MDCT of the humerus and femur in 103 untreated adult patients with AA (n = 32) and MDS (n = 71). We retrospectively reviewed the medical records of patients with AA and MDS diagnosed in the Department of Hematology/Oncology at Kameda Medical Center, Kamogawa, Japan, from July 2008 to June 2014. A retrospective review of clinical and laboratory features, including complete blood count, % bone marrow blasts, chromosomal analysis, and International Prognostic Scoring System (IPSS), was performed. WHO classification of MDS patients was as follows: RA (n = 22), RARS (n = 2), RCMD (n = 17), RAEB 1 (n = 18), RAEB 2 (n = 11), and MDS unclassified (n = 1). Overall survival (OS) and leukemia-free survival (LFS) were analyzed in 71 MDS patients by the Kaplan–Meier method and differences between curves were calculated by two-sided log-rank test. CT image acquisition and image analysis: Non-enhanced CT examinations were performed from the base of the skull down to the knee joint with an MS-CT scanner (AQUILION 64; Toshiba, Tokyo, Japan). The bony canals of the humeral and femoral bones were visualized by coronal and sagittal axis image reconstruction. The effective radiation dose associated with whole-body MD-CT was 10.1 mSv (ICRP 26). The dose was comparable to whole-body CT (2.4 mSv). Medullary CT density of the humerus and femur were measured and the results are expressed in Hounsfield units (HU). As the normal adult bone marrow was composed of rich adipocytes and called yellow marrow, it is represented by a low-density CT value between –30 and –100 HU. A value above –30 HU observed in long bony canals was considered to indicate a high-density lesion. The medullary pattern of the appendicular skeleton was categorized as follows: (1) fatty, showing a low signal density marrow; (2) focal, showing abnormally focal high-density lesions; (3) diffuse, showing uniformly high-density marrow. Results: All 15 patients with AA showed a fatty (n = 12, 37.5%) or focal (n = 20, 62.5%) pattern in medullary AS on MDCT, and none showed a diffuse pattern. Among the 71 patients with MDS, 22 (30.9%) had a fatty pattern, 32 (45.1%) had a focal pattern, and 17 (23.9%) had a diffuse pattern. Seventeen patients with diffuse infiltration pattern on MDCT had significantly shorter LFS (P  〈  0.01, P = 0.02) compared to 23 patients with fatty pattern and 32 patients with focal medullary pattern (median LFS: 18 months vs. not reached vs. not reached, respectively). Seventeen patients with a diffuse infiltration pattern on MDCT had significantly shorter OS (P = 0.04) compared to 23 patients with a fatty pattern, but the difference was no significant compared to 32 with a focal medullary pattern (P = 0.15) (median OS: 22 months vs. not reached vs. not reached, respectively). The characteristics of the patients with diffuse pattern did not differ significantly in terms of sex, age, WBC count, platelet count, karyotype, WT1, or IPSS classification from those of patients with a fatty or focal pattern, but patients with a diffuse infiltration pattern on MDCT had a significantly low hemoglobin concentration compared to those with a fatty or focal medullary pattern (P = 0.03). Conclusions: This study showed that MDCT imaging of the appendicular skeleton provided important information for the diagnosis and prognosis of patients with MDS and AA. In patients with MDS, a diffuse pattern on MDCT emerged as an independent negative prognostic indicator on LFS and OS. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.5602.5602
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 5
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    Clinical Significance of Bone Marrow Imaging of Appendicular Skeletons By Low-Dose Multi-Detector Computed Tomography in Patients with Bone Marrow Failure Syndrome
    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 1690-1690
    Details
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 1690-1690
    Abstract: Background: Aplastic anemia (AA), paroxysmal nocturnal hemoglobinuria (PNH) and myelodysplastic syndrome (MDS) are the heterogeneous group of bone marrow failure syndrome (BMFs). AS they often show profound hypocellular marrow, the diagnosis is often difficult by bone marrow and laboratory examination alone. Red to yellow marrow conversion occurs with age in the appendicular skeleton (AS), where red marrow is converted to yellow marrow until the age of early 20s. Although abnormal distribution of red marrow in appendicular skeleton were previously reported in small series of patients with MDS, leukemia and lymphoma by MRI, no further study has published so far. Here, we examined distribution of red marrow in AS by low-dose multi-detector CT (MDCT) in BMFs patients, and analyzed the relationship between the abnormal medullary pattern in AS and laboratory variables. The relationship between the MDCT pattern and subsequent development of leukemic transformation on survivals was analyzed in patients with BMFs. Patients: We retrospectively reviewed the medical records of 138 untreated patients (AA n=36, PNH n=5, and MDS n=97) with BMFs diagnosed in the Department of Hematology/Oncology at Kameda Medical Center, Kamogawa, Japan, from July 2008 to June 2014. Follow-up MDCTs were evaluated in 28 MDS patients when they were diagnosed as overt AML (MDS/tAML). Retrospective review of clinical and laboratory features including complete blood count, % of bone marrow blast, chromosomal analysis, and International Prognostic Scoring System (IPSS) at diagnosis was performed. WHO classification of patients with MDS was as follows: RCUD (n=21), RARS (n=2), RCMD (n=26), RAEB (n=43), and, MDS unclassified (MDS-U) (n=5). Leukemia-free survival (LFS) and overall survival (OS) were analyzed in 73 patients with MDS who were ≥65 years of age and ineligible for allogeneic stem cell transplantation (allo SCT) by the Kaplan-Meier. CT image acquisition and Image analysis: Non-enhanced CT examinations were performed from the skull to the knees by MDCT scanner (Aquilion 64, Tohshiba, Tokyo, Japan). Bony canal of humeral and femoral bone were visualized by coronal and sagittal axis image reconstruction. Medullary CT density of humerus and femurs were measured and the results were expressed as Hounsfield unit (HU). As the normal adult bone marrow was composed of rich adipocytes and called yellow marrow, it is represented by low density CT value between -30 to -100 HU. The value above -30 HU observed in long bony canals was considered as high density. Medullary pattern of AS were categorized as follows: (1) fatty pattern; showing a low signal density marrow (2) focal pattern; showing abnormally focal high density lesions (3) diffuse pattern; showing uniformly high density marrow. Results: All 36 patients with AA showed a fatty (n=13, 36.1%) or focal (n=23, 63.9%) pattern in medullary AS on MDCT, and none of them showed diffuse pattern. Five patients with PNH showed as follows: fatty/focal/diffuse, 1/3/1. Ninety-seven patients with MDS showed as follows: fatty/focal/diffuse, 24/46/27. Patients with MDS who showed diffuse pattern had a significantly low hemoglobin concentration compared to those with fatty or focal pattern (p=0.03). Among the patients with MDS, most of the patients with RCUD (n=21), RARS (n=2), RCMD (n=26), MDS-U (n=5) showed the fatty or focal pattern (fatty or focal/diffuse pattern; RCUD (18/3), RARS (2/0), RCMD (21/5), MDS-U (5/0)), but approximately half (46%) of patients with RAEB showed diffuse pattern (fatty/focal/diffuse pattern; 7/17/19). In addition, patients with transformed to MDS/tAML showed either focal (n=10, 35.7%) or diffuse (n=18, 64.3%) pattern and none of them showed fatty pattern. In 73 patients with MDS who were ≥65 years of age and ineligible for allo SCT, the group with focal or diffuse pattern had significantly shorter LFS and OS compared to the group with fatty pattern (p=0.01, p=0.05, respectively). Patients with focal pattern in AS showed longer LFS than those with diffuse pattern (p=0.05), but difference was not statistically significant in OS (p=0.22). Conclusions: This study showed that MDCT imaging of the appendicular skeletons provided important information for the diagnosis and prognosis of patients with BM. In patients with MDS, focal or diffuse pattern on MDCT showed negative prognostic impact on LFS and OS, and these patterns appeared to reflect the status of disease. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V126.23.1690.1690
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 6
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    Transcriptome analysis offers a comprehensive illustration of the genetic background of pediatric acute myeloid leukemia
    American Society of Hematology ; 2019
    In:  Blood Advances Vol. 3, No. 20 ( 2019-10-22), p. 3157-3169
    Details
    In: Blood Advances, American Society of Hematology, Vol. 3, No. 20 ( 2019-10-22), p. 3157-3169
    Abstract: Using RNA-seq in pediatric AML patients, 5 gene rearrangements were newly identified, including NPM1 and RUNX1 gene rearrangements. RNA-seq unmasked the complexity of gene alterations in pediatric AML by identifying disease-causing alterations in nearly all patients.
    Type of Medium: Online Resource
    ISSN: 2473-9529 , 2473-9537
    URL: Article
    DOI: 10.1182/bloodadvances.2019000404
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 7
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    Utility of Interim and Post-Therapy PET/CT in T-Cell and NK-Cell Lymphoma: A Single Institutional Analysis over 9 Years
    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 3915-3915
    Details
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 3915-3915
    Abstract: Introduction: Positron emission tomography combined with computed tomography (PET-CT) is functional imaging test and has been widely used in malignant lymphoma (ML) for initial staging and monitoring response to treatment. Interim PET-CT (iPET) and post-therapy PET-CT (ePET) is also used to assess the early response and guide subsequent treatment, although its role is still controversial other than in Hodgkin's disease and diffuse large B cell lymphoma. Peripheral T cell lymphoma (PTCL) and natural killer (NK) cell lymphomas are relatively rare and heterogeneous types of ML. The prognosis of T and NK (T/NK) cell lymphoma is poor and no standard treatment is available. Therefore, there is a need to find better prognostic factors or tools for these patients. PET-CT is both sensitive and specific for initial staging of T/NK cell lymphoma, although there have been few studies using i- and ePET in these lymphomas. We investigated the prognostic value of i- and ePET in T/NK cell lymphoma in a retrospective single-center study. Methods: Between June 2006 and June 2015, 79 patients with T/NK cell lymphomas had iPET after 2 to 4 courses of treatment and at the end of treatment at Kameda Medical Center, Japan. iPET was performed just before the next cycle of treatment. Treatment responses were scored according to the Deauville score using a 5-point scale (DS). We defined DS scores 1 - 3 as complete metabolic response (CMR). Standardized uptake value (SUV) measurement was normalized relative to the injected dose and lean body mass. The SUV was measured for all lesions and the highest value for each scan was recorded as maximum SUV (SUVmax). These lesions were identified as indicator lesions. For mid- and end-treatment scans, we recorded the change in SUVmax (DSUV), comparing the index lesion and the highest SUVmax in the scan regardless of the index lesion. Differences in overall survival (OS) and progression-free survival (PFS) were calculated by two-sided log-rank test. PET-CT status was assessed for its ability to predict PFS and OS. Results: The study population consisted of 48 men and 31 women with a median age of 70 years. The most frequent lymphoma diagnoses were peripheral T cell lymphoma-not otherwise specified (PTCL-NOS) (n  = 29), angioimmunoblastic T cell lymphoma (AITL) (n  = 21), anaplastic large cell lymphoma (ALCL) (n  = 6), adult T cell leukemia/lymphoma (ATLL) (n  = 12), enteropathy-associated T cell lymphoma (EATL) (n  = 2), and NK/T cell lymphoma (NKTCL) (n  = 9). Most patients except for ATLL and NK cell lymphoma were instituted with the CHOP-like regimen. Baseline PET scan was positive in all cases and median SUVmax was 13.7 (range, 2.6 - 37.4). iPET results were negative in 17 cases (26%), and ePET results were negative in 22 of 46 (48%) cases. With a median follow up of 30 months, 5-year PFS rate was 66% for obtaining CMR vs. 9.2% for not obtaining CMR (P   〈  0.001). The percentages of patients that obtained CMR were 48% (14/29), 62% (13/21), 67% (4/6), 33% (3/9), 50% (1/2), and 56% (5/9) for those with PTCL-NOS, AITL, ALCL, ATLL, EATL, and NKTCL, respectively. The patients who obtained CMR showed significantly longer PFS and OS compared to those who did not. We also analyzed DSUVmax. Using the ROC curve, DSUVmax values between baseline and iPET of 〉  62% and 〉  85% were predictive of better PFS and OS (sensitivity 96%, specificity 67%, area under the curve (AUC) 0.89, 95% confidence interval (CI) = 0.82 - 0.97 and sensitivity 49%, specificity 97%, AUC 0.80, 95% CI = 0.70 - 0.90, respectively). We examined the positive and negative predictive values (PPV and NPV) and accuracy in predicting PFS and OS in 66 patients who underwent iPET. Of 35 iPET-positive patients, 31 (89%) showed progression, and 26 (74%) died during the follow-up. On multivariate Cox regression analysis, obtaining CMR at iPET emerged as an independent prognostic factor for PFS and OS (P 〈 0.001 and P 〈 0.001, respectively). Conclusions: Our data suggest that patients with positive results on i- or ePET should be considered candidates for intensive therapeutic strategies to improve their clinical outcome. Large prospective studies of patients with tumors of a homogeneous histological subtype within the T/NK cell lymphoma, treated with a uniform protocol, and evaluated on the basis of standardized criteria are warranted. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V126.23.3915.3915
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
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  • 8
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    Clinical Significance of Circulating Plasma Cells in Myeloma: Multiparameter Flow Cytometric Analysis
    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 5352-5352
    Details
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 5352-5352
    Abstract: [Introduction] It has been reported that clonal circulating plasma cells (cPC) were detected in patients with multiple myeloma (MM) and other plasma cell dyscrasias (PCD), and their detection has been shown to be a risk in newly diagnosed MM and shortened progression free survival in patients smoldering MM (sMM). It is unclear that the detection of cPCs in peripheral blood may be a simple reflection of tumor burden of bone marrow plasma cells or may represent different. This study was performed to evaluate the clinical utility of quantifying clonal cPC using 6-color FCM in patients with MGUS, SMM, and symptomatic MM (symMM) at diagnosis (Dx). They were compared with bone marrow samples (BM PCs) simulatneously analyzed in the same way. Besides we evaluated the transition of quantification of clonal cPC of PB samples at various stages after treatment. [Materials and Methods] We analyzed 280 peripheral blood (PB) samples from 194 patients with PCD (MGUS, SMM, and symMM; n  = 34/39/121, respectively) diagnosed at the Department of Hematology/Oncology, Kameda Medical Center and Kanazawa University Hospital from January 2012 to July 2015. Similarly, we analyzed 30 PB samples from 30 healthy controls. Mononuclear cells (MNC) were isolated from PB by density gradient centrifugation and stained with antibodies to CD45, CD38, CD19, CD138, CD56, and cytoplasmic kappa and lambda immunoglobulin (Ig) light chains. The cells were collected using a Beckman-Coulter NAVIOS and analyzed using Kaluza software. The gating strategy employed was expression of CD38, CD45, CD138, and cytoplasmic Ig light chains. Clonal cPC was defined as the population of CD138+, CD38+ CD45-~±, and CD19-. To confirm the clonality of these cells, light chain restriction of cytoplasmic Ig was used (κ/λ 〉 4 or 〈 0.5) using the 2nd tube. Quantification was performed by acquiring 〉  2×106 total events. At least ≥ 20 clonal cPC were required for the analysis. [Results] We analyzed clonal cPC of 194 PB samples with MGUS, SMM, and symMM (n  = 34/39/121, respectively) at diagnosis (Dx). The mean values of clonal cPC were: MGUS, 2.67×10-5/MNC (range, 0 - 3.0×10-4); SMM, 2.43×10-4/MNC (range, 0 - 3.6×10-3); symMM, 6.99×10-3/MNC (range, 0 - 1.5×10-1). The number of clonal cPC was significantly higher in SMM than MGUS, and in symMM than SMM (P   〈  0.001). In healthy controls, the mean value of cPC without CD19 expression was 3.84×10-6/MNC (range, 0 - 1.3×10-5). Although these cPC lacked the expression of CD19, none of the samples did not show the light chain restriction of cytoplasmic Ig. Next, we analyzed clonal cPC of 185 PB samples (Dx, n  = 85; partial response [PR], n  = 31; very good partial response [VGPR] , n  = 25; complete response [CR], n  = 22; progressive disease [PD] , n  = 23) in various treatment responses of symMM. The mean values of clonal cPC were: at Dx, 6.99×10-3/MNC (range, 0 - 1.5×10-1); at PR, 5.19×10-5/MNC (range, 0 - 3.5×10-4); at VGPR, 9.79×10-5/MNC (range, 0 - 9.7×10-4); at CR, 1.90×10-5/MNC (range, 0 - 1.2×10-4); at PD, 1.94×10-3/MNC (range, 0 - 3.9×10-2). The number of clonal cPC was significantly higher at Dx than from PR to CR, and significantly lower in CR than from PR to VGPR (P   〈  0.01, P  = 0.23, respectively). However, the number of clonal cPC was not significantly different between PR and VGPR (P  = 0.61). When patients with PCD at Dx were divided into high and low clonal cPC groups (high cPC ≥ 1.0x10-4/MNC and low cPC  〈  1.0x10-3/MNC), the number of the high cPC group was as follows: (MGUS 2/35 (5.7%), SMM 9/38 (23.7%), symMM 35/85 (41.2%)) (P 〈 0.01). In symMM patients, clinical characteristics were comparable between the two groups except for bone marrow PCs. A total of 133 bone marrow samples (BM PCs) were measured simultaneously with PB samples at Dx. The number of clonal cPC tended to be related to the percentage of clonal plasma cells/total plasma cells in BM in symMM (R = 0.579), but no such relation was observed in MGUS and SMM (R = 0.112, -0.03). [Conclusions] In conclusion, quantification of clonal cPC by 6-color FCM is feasible and appears to reflect the tumor burden in patients with newly diagnosed MM and sMM, but not in patients after treatment. Further studies using quantification of clonal cPC combined with other hematological parameters will identify patients at high risk of early progression and poor prognosis. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V126.23.5352.5352
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 9
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    Immunoglobulin Heavy/Light Chain Immunoassays for Response Evaluation in Multiple Myeloma: Comparison with Immunofixation, Serum Free Light Chain, and Multicolor Flow- Cytometry
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 3366-3366
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 3366-3366
    Abstract: BACKGROUND: Monitoring of multiple myeloma (MM) patients is required to assess and determine the treatment response. The serum immunoglobulin (Ig) heavy/light chain immunoassays are a new method that enables separate quantification of the different light chain types of each Ig class, i.e., IgGk, IgGl, IgAk, and IgAl. Although the contribution of these tests to disease evaluation has been assessed, available data are still limited. Here, we compared the serum Ig heavy/light chain immunoassays with the conventional methods for disease evaluation. PATIENTS AND METHODS: Three hundred and three samples were obtained from a total of 101 patients with IgG and IgA type MM recruited at Kameda Medical Center and Kanazawa University Hospital. The median age of the patients was 68 years (range: 44 – 89). The median follow-up was 36 months (range: 2.5 – 189.6). The proportions of patients in International Scoring System (ISS) stages I, II, and III were 25%, 35%, and 40%, respectively. Paraprotein type was IgG in 64 patients (44 Gk, 20 Gl) and IgA in 37 (20 Ak, 17 Al). Samples were taken at various times after treatment and analyzed retrospectively with serum Ig heavy/light chain immunoassays (Hevylite®; Binding Site, Birmingham, UK) on a SPAPLUS® turbidimeter. The heavy/light chain ratio (HLCR) was calculated with the Ig' k (either G or A) as the numerator and compared to normal ranges (IgGk:3.84-12.07g/L; IgGl:1.91-6.74g/L; IgGk/IgGl: 1.12-3.21; IgAk:0.57-2.08g/L; IgAl:0.44-2.04g/L; IgAk/IgAl:0.78-1.94). Results were compared to serum protein electrophoresis (SPEP), immunofixation electrophoresis (IFE), and serum free light chain immunoassays (FLC). HLC-pair suppression was defined as the uninvolved immunoglobulin of the same isotype 50% below the lower limit of the normal range (IgGk, IgGl, IgAk, IgAl). Residual neoplastic plasma cells (MM-PCs) in bone marrow samples were assessed by multicolor flow cytometry (MFC) simultaneously in 140 samples from 64 patients at very good partial response (VGPR), complete response (CR), and stringent CR (sCR). The MFC negativity was defined at a level of 〈  10-4 MM-PCs. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan–Meier method, and survival was compared using the log rank test. RESULTS: Myeloma responses were assessed serially after induction therapy and were assigned according to international response criteria. Patients' samples at various responses were: sCR, n = 86 (28%); CR, n = 31 (10%); VGPR, n = 116 (38%); and PR, n = 70 (23%). Normal HLCR was obtained at sCR, CR, and VGPR in 73 (85%), 28 (90%), and 69 (59%) cases, respectively. Discordance in the depth of response between standard electrophoretic methods and HLCR was more commonly seen in IgG compared to IgA MM; possibly reflecting the dose dependent half life of IgG immunoglobulins. In the sera from patients who achieved a CR or better, abnormal HLCR and FLC ratio were seen at rates of 12.8% and 26.5%, respectively. Discordance between normalization of HLCR and FLC ratio was seen in 42% of patients with a CR or better; however, a good correlation between normalization of HLCR and FLC ratio was still observed (Fisher's exact test, P = 0.004). Among the 71 sera from patients with a CR or better in which simultaneous MFC data were available, 16 (22.5%) sera were MFC-negative. Among the patients who achieved a VGPR or better, patients with a normal HLCR had fewer MM-PCs than those with an abnormal HLCR (median 9.8x10-4vs. 46.0x10-4, respectively, P=0.062), although the difference was not statistically significant. Abnormal HLCR in CR samples was seen more frequently in patients with IgA type (19%) than IgG type (7.7%). Longer PFS and OS were observed in patients who achieved HLCR normalization at best response than in those who did not (PFS; 83.8 months vs. 41.8 month, respectively, P = 0.016 and OS; not reached vs. not reached, P = 0.018). When patients at best response were divided into with or without uninvolved HLC pair suppression, the latter group showed significantly better OS compared to the former group (not reached vs. not reached, P=0.019). CONCLUSIONS: The findings presented here suggest the potential usefulness of heavy/light chain immunoassays for monitoring of myeloma response in patients with IgA myeloma and residual MM-PC assessment at VGPR or better. Presence of abnormal HLCR at best response and HLC pair suppression were also associated with poorer survival. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.3366.3366
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 10
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    Endoscopic Ultrasound-Guided Fine Needle Aspiration Biopsy for Diagnosis of Intra-Abdominal Lymphoma without Accessible Peripheral Lymphadenopathy
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 5380-5380
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 5380-5380
    Abstract: Introduction: Endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) is considered the procedure of choice for the diagnosis and staging of intra-abdominal non-Hodgkin’s lymphoma (NHL) without accessible peripheral lymphadenopathy. However, diagnosis and subclassification lymphoma by FNAB is often challenging due to variable cellularity and lack of architecture. Recent advances of ancillary techniques such as immunohistochemical staining, flowcytometry (FCM), fluorescence in situ hybridization (FISH) analysis and molecular analysis allowed classify lymphoma more precisely, although sufficient information can be obtained through this procedure remained undetermined. The present study was performed to evaluate the yield of EUS-FNAB using a standard 19 or 22-gauge needle for diagnosis and subclassification of lymphoma, assessing the feasibility of immunohistological, FCM, molecular and cytogenetic assessments. Methods: Between April 2008 and July 2014, 90 patients with malignant lymphoma who had an intra-abdominal mass without accessible peripheral lymphadenopathy underwent EUS-guided fine needle aspiration biopsy at our hospital. All patients received positron emission tomography/computed tomography and had 2-deoxy-2-(18F)fluoro-D-glucose-avid lesions in abdomen before examination. The aspirated materials were processed for flowcytometry (FCM), molecular analysis of immunoglobulin heavy (IgH) and T-cell receptor (TCR) gene rearrangement, cytogenetic analysis by conventional G banding, and FISH analysis, in addition to standard histopathological studies. Patients’ baseline data, including age, sex, laboratory examinations, imaging studies, and final diagnosis of lymphoma, were collected and examined to determine the feasibility and sensitivity for diagnosis and subclassification of lymphoma. Results: The mean of the diameter of mass was 37mm (9.7-149mm). Among the 90 patients, conventional G banding, FCM analysis, standard cytogenetic analysis, and FISH were successfully performed in 67 (74%), 78 (87%), 44 (49%), and 58 (64%) cases, respectively. G banding analysis were successful in 45 patients (67%) that showed normal karyotype in 5 cases (7%), t(14;18)(q32;q21) in 7 cases (10%), t(8;14)(q24;q32) in one case, and complex abnormality in 32 cases (48%), respectively. FCM analysis showed immunoglobulin light chain restriction in 48 cases (62%) and were diagnosed as B-cell lymphoma. FCM could not determine the T-cell clonality. Molecular analyses for TCR and/or IgH receptor rearrangements were successful in 35 patients (83%), 31 rearranged in IgH and 4 rearranged in TCR, respectively. There were 32 cases with IgH/Bcl2 fusions by FISH analysis, 26 cases in follicular lymphoma (FL) and 6 cases in diffuse large B-cell lymphoma (DLBCL), respectively. IgH/Bcl6 fusion was seen in 2 case of DLBCL and IgH/C-myc fusion was seen in 1 case of Burkitt lymphoma (BL). Finally, our cohort included 82 B-cell lymphomas (91%) and 8 T-cell lymphomas (9%). Subclassification of lymphoma in accordance with WHO system included 40 cases of FL, 39 cases of DLBCL, one case of BL, 2 cases of lymphoblastic lymphoma, 7 cases of peripheral T cell lymphoma not specified, and one case of angioimmunoblastic lymphoma. Although all of the outpatients were hospitalized until the day after biopsy, there were no serious complications related to this procedure like bleeding, perforation, ileus, and infection. Conclusions: EUS-FNAB using a standard 19 or 22-gauge needle is safe and feasible and has high diagnostic value for subclassification of intra-abdominal lymphoma without accessible peripheral lymphadenopathy. With the use of simultaneous immunophenotyping, molecular, and cytogenetic studies, lymphoma subclassification was possible in most of the cases. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.5380.5380
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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    detail.hit.zdb_id: 80069-7
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