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Integrated genetic and clinical prognostic factors for aggressive adult T-cell leukemia/lymphoma

Kameda, Takuro ; Kataoka, Keisuke ; Kamiunten, Ayako ; [et al.]

Ferrata Storti Foundation (Haematologica) ; 2023

In: Haematologica Vol. 108, No. 8 ( 2023-02-16), p. 2178-2191

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In: Haematologica, Ferrata Storti Foundation (Haematologica), Vol. 108, No. 8 ( 2023-02-16), p. 2178-2191

Abstract: The prognosis of aggressive adult T-cell leukemia/lymphoma (ATL) is poor, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment. In order to identify favorable prognostic patients after intensive chemotherapy, and who therefore might not require upfront allo-HSCT, we aimed to improve risk stratification of aggressive ATL patients aged 〈 70 years. The clinical risk factors and genetic mutations were incorporated into risk modeling for overall survival (OS). We generated the m7-ATLPI, a clinicogenetic risk model for OS, that included the ATL prognostic index (PI) (ATL-PI) risk category, and non-silent mutations in seven genes, namely TP53, IRF4, RHOA, PRKCB, CARD11, CCR7, and GATA3. In the training cohort of 99 patients, the m7-ATLPI identified a low-, intermediate-, and highrisk group with 2-year OS of 100%, 43%, and 19%, respectively (hazard ratio [HR] =5.46; P 〈 0.0001). The m7-ATLPI achieved superior risk stratification compared to the current ATL-PI (C-index 0.92 vs. 0.85, respectively). In the validation cohort of 84 patients, the m7-ATLPI defined low-, intermediate-, and high-risk groups with a 2-year OS of 81%, 30%, and 0%, respectively (HR=2.33; P=0.0094), and the model again outperformed the ATL-PI (C-index 0.72 vs. 0.70, respectively). The simplified m7-ATLPI, which is easier to use in clinical practice, achieved superior risk stratification compared to the ATLPI, as did the original m7-ATLPI; the simplified version was calculated by summing the following: high-risk ATL-PI category (+10), low-risk ATL-PI category (−4), and non-silent mutations in TP53 (+4), IRF4 (+3), RHOA (+1), PRKCB (+1), CARD11 (+0.5), CCR7 (−2), and GATA3 (−3).

Type of Medium: Online Resource

ISSN: 1592-8721 , 0390-6078

URL: Article

DOI: 10.3324/haematol.2022.281510

Language: Unknown

Publisher: Ferrata Storti Foundation (Haematologica)

Publication Date: 2023

detail.hit.zdb_id: 2186022-1

detail.hit.zdb_id: 2030158-3

detail.hit.zdb_id: 2805244-4

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Effects of mogamulizumab in adult T‐cell leukemia/lymphoma in clinical practice

Sekine, Masaaki ; Kubuki, Yoko ; Kameda, Takuro ; [et al.]

Wiley ; 2017

In: European Journal of Haematology Vol. 98, No. 5 ( 2017-05), p. 501-507

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In: European Journal of Haematology, Wiley, Vol. 98, No. 5 ( 2017-05), p. 501-507

Abstract: The efficacy of mogamulizumab in adult T‐cell leukemia/lymphoma ( ATLL ) was reported in a previous phase 2 study. Compared with patients in clinical trials, however, most patients in real‐life settings have demonstrated worse outcomes. Method We retrospectively analyzed 96 patients with relapsed/refractory ATLL who received mogamulizumab treatment. Results Relapsed/refractory ATLL patients with a median age of 70 years received a median of five courses of mogamulizumab. Hematologic toxicity and skin rash were the most common adverse events, and both were manageable. Of 96 patients, 87 were evaluable for efficacy. The overall response rate was 36%, and the median progression‐free survival ( PFS ) and overall survival ( OS ) from the start of mogamulizumab therapy were 1.8 and 4.0 months, respectively. Of the original 96 patients, only 25 fulfilled the inclusion criteria of the phase 2 study. Those who met the criteria demonstrated longer median PFS and OS durations of 2.7 and 8.5 months, respectively. The median OS from diagnosis in relapsed/refractory ATLL patients receiving mogamulizumab was 12 months, longer than the 5.8 months in a historical cohort without mogamulizumab. Conclusion In clinical practice, mogamulizumab exhibited antitumor activity in patients with relapsed/refractory ATLL , with an acceptable toxicity profile. Mogamulizumab therapy improved the OS of ATLL patients.

Type of Medium: Online Resource

ISSN: 0902-4441 , 1600-0609

URL: Issue

URL: Article

DOI: 10.1111/ejh.2017.98.issue-5

DOI: 10.1111/ejh.12863

Language: English

Publisher: Wiley

Publication Date: 2017

detail.hit.zdb_id: 2027114-1

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Acute myeloid leukemia in clinical practice: a retrospective population-based cohort study in Miyazaki Prefecture, Japan

Matsunaga, Takuya ; Yamashita, Kiyoshi ; Kubuki, Yoko ; [et al.]

Springer Science and Business Media LLC ; 2012

In: International Journal of Hematology Vol. 96, No. 3 ( 2012-9), p. 342-349

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In: International Journal of Hematology, Springer Science and Business Media LLC, Vol. 96, No. 3 ( 2012-9), p. 342-349

Type of Medium: Online Resource

ISSN: 0925-5710 , 1865-3774

URL: Article

DOI: 10.1007/s12185-012-1146-2

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2012

detail.hit.zdb_id: 2028991-1

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Early/prefibrotic primary myelofibrosis in patients who were initially diagnosed with essential thrombocythemia

Kamiunten, Ayako ; Shide, Kotaro ; Kameda, Takuro ; [et al.]

Springer Science and Business Media LLC ; 2018

In: International Journal of Hematology Vol. 108, No. 4 ( 2018-10), p. 411-415

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In: International Journal of Hematology, Springer Science and Business Media LLC, Vol. 108, No. 4 ( 2018-10), p. 411-415

Type of Medium: Online Resource

ISSN: 0925-5710 , 1865-3774

URL: Article

DOI: 10.1007/s12185-018-2495-2

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2018

detail.hit.zdb_id: 2028991-1

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Prognosis of Indolent Adult T-Cell Leukemia/Lymphoma

Kameda, Takuro ; Shide, Kotaro ; Tahira, Yuki ; [et al.]

MDPI AG ; 2022

In: Viruses Vol. 14, No. 4 ( 2022-03-29), p. 710-

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In: Viruses, MDPI AG, Vol. 14, No. 4 ( 2022-03-29), p. 710-

Abstract: A retrospective chart survey of the clinical features of indolent adult T-cell leukemia/lymphoma (ATL) was conducted in the Miyazaki Prefecture, Japan. This study enrolled 24 smoldering-type ATLs, 10 favorable chronic-type ATLs, and 20 unfavorable chronic-type ATLs diagnosed between 2010 and 2018. Among them, 4, 3, and 10 progressed to acute-type ATLs during their clinical course. The median survival time (MST) in smoldering-type ATL and favorable chronic-type ATL was not reached, and their 4-year overall survival (OS) was 73% and 79%, respectively. Compared with this, the prognosis of unfavorable chronic-type ATL was poor. Its MST was 3.32 years, and the 4-year OS was 46% (p = 0.0095). In addition to the three features that determine the unfavorable characteristics of chronic-type ATL, namely, increased lactate dehydrogenase, increased blood urea nitrogen, and decreased albumin, the high-risk category by the indolent ATL-Prognostic Index, which was defined by an increment of soluble interleukin-2 receptor (sIL2-R) of 〉 6000 U/mL, could explain the poor prognosis in indolent ATL patients. The level of sIL-2R might be an indicator of the initiation of therapy for indolent ATL.

Type of Medium: Online Resource

ISSN: 1999-4915

URL: Article

DOI: 10.3390/v14040710

Language: English

Publisher: MDPI AG

Publication Date: 2022

detail.hit.zdb_id: 2516098-9

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Real-World Data on Clinical Features, Outcomes, and Prognostic Factors in Multiple Myeloma from Miyazaki Prefecture, Japan

Akizuki, Keiichi ; Matsuoka, Hitoshi ; Toyama, Takanori ; [et al.]

MDPI AG ; 2020

In: Journal of Clinical Medicine Vol. 10, No. 1 ( 2020-12-30), p. 105-

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In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 1 ( 2020-12-30), p. 105-

Abstract: The prognosis of multiple myeloma (MM) has improved with the introduction of novel agents. These data are largely derived from clinical trials and might not reflect real-world patient outcomes accurately. We surveyed real-world data from 284 patients newly diagnosed with MM between 2010 and 2018 in Miyazaki Prefecture. The median follow-up period was 32.8 months. The median age at diagnosis was 71 years, with 68% of patients aged 〉 65 years. The International Staging System (ISS) stage at diagnosis was I in 18.4% of patients, II in 34.1%, and III in 47.5%. Bortezomib-containing regimens were preferred as initial treatment; they were used in 147 patients (51.8%). In total, 80% of patients were treated with one or more novel agents (thalidomide, lenalidomide, or bortezomib). Among 228 patients who were treated with novel agents as an initial treatment, the overall response rate (partial response (PR) or better) to initial treatment was 78.4%, and the median time to next treatment (TTNT) was 11.6 months. In the multivariate analysis, PR or better responses to initial treatment were independently favorable prognostic factors for TTNT. The median survival time after initial therapy for patients with novel agents was 56.4 months and 3-year overall survival (OS) was 70.4%. In multivariate analysis, ISS stage I/II disease and PR or better response to initial treatment, and autologous stem cell transplantation (ASCT) were identified as independent prognostic factors for overall survival (OS).

Type of Medium: Online Resource

ISSN: 2077-0383

URL: Article

DOI: 10.3390/jcm10010105

Language: English

Publisher: MDPI AG

Publication Date: 2020

detail.hit.zdb_id: 2662592-1

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Thrombohemorrhagic events, disease progression, and survival in polycythemia vera and essential thrombocythemia: a retrospective survey in Miyazaki prefecture, Japan

Kamiunten, Ayako ; Shide, Kotaro ; Kameda, Takuro ; [et al.]

Springer Science and Business Media LLC ; 2018

In: International Journal of Hematology Vol. 107, No. 6 ( 2018-6), p. 681-688

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In: International Journal of Hematology, Springer Science and Business Media LLC, Vol. 107, No. 6 ( 2018-6), p. 681-688

Type of Medium: Online Resource

ISSN: 0925-5710 , 1865-3774

URL: Article

DOI: 10.1007/s12185-018-2428-0

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2018

detail.hit.zdb_id: 2028991-1

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Mogamulizumab for ATLL in Clinical Practice

Sekine, Masaaki ; Takeuchi, Masaki ; Toyama, Takanori ; [et al.]

American Society of Hematology ; 2016

In: Blood Vol. 128, No. 22 ( 2016-12-02), p. 2998-2998

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In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 2998-2998

Abstract: Introduction Adult T-cell leukemia/lymphoma (ATLL) is an aggressive peripheral T cell neoplasm that is resistant to conventional chemotherapy and carries a poor prognosis. The effect of mogamulizumab, an immunoglobulin (Ig) G1 monoclonal antibody targeting CCR4 for ATLL cells, was reported in a previous phase 2 study in which mogamulizumab monotherapy was evaluated in relapsed ATLL patients. The overall response rate (ORR), median progression-free survival (PFS) and median overall survival (OS) were 50%, 5.2 and 13.7 months, respectively. It was not stated whether these values were derived in the real world or in clinical practice. Here we evaluate the clinical impact of mogamulizumab treatment in CCR-4-positive aggressive ATLL patients in clinical practice. Patients and methods We retrospectively analyzed 101 CCR-4-positive ATLL patients who received at least one cycle of mogamulizumab infusion between March, 2012 and April, 2016 in 7 facilities in Miyazaki prefecture, an HTLV-1 endemic area in Southwestern Japan. The ORR, PFS, OS and adverse effects (AEs) were evaluated. We next compared OS in patients with at least one course of mogamulizumab therapy with that in historical control patients without mogamulizumab therapy. Results Of the 101 patients, 92 were evaluable for treatment response, survival and AEs. The median age was 70 years old (range; 45 to 90), and 52 patients (51%) were more than 70 years old. According to Shimoyama's criteria, 66 patients were classified as acute type, 32 as lymphoma type, and 3 as chronic type. All 3 chronic-type ATLL patients had at least one unfavorable risk factor. Of the 101 patients, 96 had refractory or relapsed ATLL when mogamulizumab treatment was started, and the prior treatments consisted of VCAP-AMP-VECP, CHOP, DeVIC or CHASE therapy, with an average of 2 courses. In the 5 remaining cases, mogamulizumab was administered as the initial therapy for ATLL. Mogamulizumab was administered as monotherapy in 87 cases (86%), and as combination therapy with other drugs in 14 cases (14%). The ORR was 37%, including a complete remission rate of 19%. The median PFS and OS were 1.8 and 4.2 months, respectively. Among the 101 patients treated with mogamulizumab, only 26 (26%) fulfilled the inclusion criteria of the phase 2 clinical study. Among patients who met those inclusion criteria, the median PFS and OS were 6.0 and 8.4 months, respectively. The use of mogamulizumab improved OS in clinical practice. The median OS of patients receiving mogamulizumab therapy was 12 months, whereas that of patients who did not receive mogamulizumab in the historical cohort was 8.4 months. Hematologic toxicity and skin rash were the most common AEs, and both were manageable Conclusion Mogamulizumab therapy showed clinically meaningful activity in ATLL patients, with an acceptable toxicity in clinical practice. Disclosures No relevant conflicts of interest to declare.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.2998.2998

RVK:

XA 33000

RVK:

XA 10000

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

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Higher average chemotherapy dose intensity improves prognosis in patients with aggressive adult T‐cell leukemia/lymphoma

Sekine, Masaaki ; Kameda, Takuro ; Shide, Kotaro ; [et al.]

Wiley ; 2021

In: European Journal of Haematology Vol. 106, No. 3 ( 2021-03), p. 398-407

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In: European Journal of Haematology, Wiley, Vol. 106, No. 3 ( 2021-03), p. 398-407

Abstract: Adult T‐cell leukemia/lymphoma (ATL) is an aggressive peripheral T‐cell lymphoma with poor prognosis. We retrospectively reviewed the medical records of 312 patients with aggressive ATL and analyzed the effect of chemotherapy dose intensity on prognosis in clinical practice. Result As first‐line therapy, 62 patients underwent best supportive care (BSC) or single‐agent chemotherapy, and 235 underwent intensive chemotherapy. The median survival time (MST) was 0.58 years in the 312 total patients, and 0.13 years and 0.75 years in the BSC/single‐agent chemotherapy group and intensive chemotherapy group, respectively. The median average relative dose intensity (ARDI) of patients who received intensive chemotherapy was 60%. We divided patients into 3 groups according to ARDI. Those in the top tertile of ARDI (ARDI ≥ 75%, n = 82) had better overall survival compared with those in the intermediate tertile (45% ≤ ARDI 〈 75%, n = 79) ( P 〈 .0001), with MSTs of 4.69 and 0.75 years, respectively. The occurrence of organ dysfunction and infectious complications was comparable between the two ARDI groups. Conclusion Higher ARDI improves prognosis in patients with aggressive ATL in clinical practice.

Type of Medium: Online Resource

ISSN: 0902-4441 , 1600-0609

URL: Issue

URL: Article

DOI: 10.1111/ejh.v106.3

DOI: 10.1111/ejh.13565

Language: English

Publisher: Wiley

Publication Date: 2021

detail.hit.zdb_id: 2027114-1

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Prognostic Factor, Including Relative Dose Intensity, For Adult T-Cell Leukemia/Lymphoma In Clinical Practice

Kamiunten, Ayako ; Kitanaka, Akira ; Kubuki, Yoko ; [et al.]

American Society of Hematology ; 2013

In: Blood Vol. 122, No. 21 ( 2013-11-15), p. 1799-1799

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In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 1799-1799

Abstract: Adult T-cell leukemia/lymphoma (ATL) is an aggressive peripheral T cell neoplasm caused by human T-cell lymphotropic virus type I with very poor prognosis. The relationship between chemotherapy dose intensity and clinical outcome of ATL in clinical practice remains unclear. Patients and methods To elucidate the clinical characteristics and outcome of ATL patients, we retrospectively analyzed 118 patients diagnosed with ATL at 7 institutes in Miyazaki Prefecture, Japan from 2010 to 2012. There were 67 males and 51 females. The median age of the patients was 70 years (range 44–92). Subtypes included acute- (n=85) and lymphoma-type (n=33). One hundred one patients were treated with one of the below combination chemotherapy: (1) VCAP-AMP-VECP (LSG15); (2) CHOP (including pirarubicin (THP)-COP); and (3) non-LSG15, non-CHOP regimen. The prognostic value of the recently proposed prognostic index for ATL, namely ATL-PI (Katsuya et al. J Clin Oncol. 2012), was evaluated in this cohort. Relative dose intensity (RDI) during the first 12 weeks of therapy was calculated based on the standard regimen. Average RDI (ARDI) for LSG15 and CHOP was calculated. Results The median survival time (MST), 1- and 2-years overall survival (OS) rates of the entire cohort were 8.5 months, 35.3% and 23.0%, respectively. MSTs of patients less than 70 years and patients 70 years or older were 11.8 and 5.7 months, respectively (p=0.03). MSTs among all age groups for acute- and lymphoma- type were 8.3 and 10.0 months, respectively (p=0.445). Although ATL-PI could efficiently discriminate high-risk patients, it failed to separate the intermediate- and low-risk patients in this cohort. As almost all patients in this cohort were stage III or IV, ATL-PI was modified to exclude the Ann Arbor stage from variables. This modified ATL-PI could stratify our cohort into three distinct risk groups. MSTs were 3.9, 10.9, and 18.1 months for patients in high, intermediate, and low risk groups, respectively (P 〈 0.01). Among this cohort, 38 patients have received LSG15 and 47 patients received CHOP. Variables known to affect outcome were similar in both groups, except the age. MSTs were 11.5 and 8.1 months for patients treated with LSG15 and CHOP, respectively (p=0.206). As the median age of CHOP group is about 10 years greater than that of LSG15 group, we examined the MST in each therapy group according to the age. The MSTs for less than 70 years old were 11.7 and 21.9 months for patients treated with LSG15 and CHOP, respectively (p=0.311). Similarly, the MSTs for 70 years or older were 8.6 and 5.5 months for patients treated with LSG15 and CHOP, respectively (p=0.142). In practice, we conclude that CHOP is still a standard therapy for ATL. We next examined the RDI in each therapy groups and its relationship with OS. During the first 12 weeks, 73.7% of patients treated with LSG15 received ≥50% of planned DI, whereas 50.0% of patients treated with CHOP received ≥50% of planned DI. MSTs were significantly longer in patients treated with higher ARDI (≥50%) than that in patients with lower ARDI ( 〈 50%) (14.7 vs. 6.2 months for LSG15; p 〈 0.01, 19.0 vs. 4.0 months for CHOP; p 〈 0.01). Conclusion Our modified ATL-PI excluding the Ann Arbor stage from variables in original ATL-PI may have prognostic value for patients with ATL. In the daily practice in Japan, no superiority of LSG15 compared to CHOP could be demonstrated both in young and elderly patient groups. Reduced ARDI in the first line chemotherapy for ATL is pervasive. Considering the significantly poor outcome of patients treated with ARDI less than 50%, changes in therapy with alternative strategy such as applying mogamulizumab, relatively early in the course of treatment, may improve outcome. Disclosures: No relevant conflicts of interest to declare.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V122.21.1799.1799

RVK:

XA 33000

RVK:

XA 10000

Language: English

Publisher: American Society of Hematology

Publication Date: 2013

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

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