Follicular lymphoma. High-dose immunochemotherapy with autologous blood stem cell transplantation: Results of the first prospective study in Russia

Nesterova, Ekaterina; Кравченко, С К; Mangasarova, Yana; Baryakh, E. A.; Misyurina, Anna; Vorobyev, Vladimir I.; Пластинина, Л. В.; Чернова, Н Г; Kovrigina, А М; Obukhova, T N; Klyasova, Galina; Шевелев, А А; Костина, И Э; Гемджян, Э Г; Гапонова, Т. В.; Vorobyev, A I

doi:10.17116/terarkh201688762-71

Cited by 6 publications

(4 citation statements)

References 27 publications

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“…Эти данные значительно лучше результатов лечения без сочетания ПХТ с ритуксимабом (5-летняя БРВ и ОВ составила 23 и 41% соответственно у пациентов с ранним рецидивом ФЛ; 33 и 65% соответственно у пациентов с поздним рецидивом ФЛ). Благодаря способности ВХТ преодолевать резистентность и рефрактерность опухолевых клеток, ВХТ с аутоТСКК у больных ФЛ из группы риска (bulky + FLIPI 3-5) более эффективна в ранние сроки (в первой линии терапии) и позволяет увеличить безрецидивный интервал [16,21,22], что подтверждают полученные результаты (86% полных ремиссий после аутоТСКК при медиане наблюдения 81 мес). Роль аутоТСКК остается предметом дискуссий.…”

Section: Discussionunclassified

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Follicular lymphoma: first - line selection criteria of treatment

Nesterova¹,

Кравченко²,

Kovrigina³

et al. 2019

Terapevticheskii arkhiv

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Follicular lymphoma (FL) is a tumor that develops from the B cells of the germinal center; characterized by recurrent and remitting course of the disease, the transformation of a tumor into diffuse large B-cell lymphoma (DLBCL) is possible. In generalized lesions and progression of FL, the most commonly used courses are R-CHOP and R-B. The choice of therapy for different cytological types, clinical and laboratory parameters remains disputable. Aim. To analyze the clinical, laboratory, morphological parameters of patients with FL, who got R-B and R-CHOP therapy; determine the criteria for selecting induction therapy. Materials and methods. The study included 203 patients with FL from 2000 to 2018. R-CHOP treatment was initiated in 126 patients, 14 of whom later received high - dose therapy (HDT) (R-DHAP: rituximab, dexamethasone, cisplatin, cytarabine) without autologous stem cell transplantation (autoSCT), 21 - HDT with autoSCT; treatment of 89 patients was limited to courses of R-CHOP and maintenance therapy with rituximab, two patients (in whom the disease progressed, despite R-CHOP therapy) were assigned the mNHL-BFM-90 program. The efficacy of treatment on various treatment regimens was evaluated primarily by overall survival. Results and discussion. R-B. 77 patients received R-B therapy. Complete remission of the disease was achieved in 47/77 (61%) patients (3 of them later developed a relapse of the disease), partial remission was achieved in 15/77 (19%) patients, in 13/77 (17%) cases progression was recorded tumors. 70 patients had 1-2 cytological type of tumor, 6 patients - 3A cytological type. In cases of progression, 3 of 13 patients (46%) were diagnosed with 3A cytological type FL. Median observation (at the time of analysis) - 34 months. R-CHOP. 89 patients with FL received high - dose therapy with R-CHOP (6-8 courses) and maintenance therapy with rituximab. In 39 (44%) patients, the disease remained in remission, and in 50 (56%), a relapse of the disease developed. 50 patients had 1-2 cytological types, 39 - 3 cytological types. In cases of recurrence of FL, a 3A cytologic type (36%) was diagnosed in 18/50 patients. Median observation - 93 months. R-CHOP + HDT and autoSCT. 21 patients after the R-CHOP courses continued (due to insufficient antitumor response) high - dose chemotherapy (HDT) and auto-SCT were performed. In 18/21 (86%) cases, complete remission of the disease was achieved and maintained, in 3 (14%) cases relapse developed. 16 patients had 1-2 cytological types, 5 - 3 cytological types. Median observation - 81 months. R-CHOP + HDT without autoSCT. 14 patients started therapy under the R-CHOP program as induction therapy, but then (due to insufficient antitumor response), the treatment was continued according to the HDT without autoSCT. 11 (79%) patients are currently in remission of the disease, in 3 (21%) - there was a relapse. 10 patients had 2 cytological types of PL, 4 - 3 cytological types. 11 (79%) patients are currently in remission of the disease, in 3 (21%) - there was a relapse. Median observation - 80 months. 7-year OS of patients with FL on RB therapy was 89% (95% CI 75-99), on R-CHOP therapy - 85% (95% CI 73-90), on R-CHOP + HDT and autoSCT - 87% (95% CI 57-100), on R-CHOP + HDT without autoSCT - 82%. 7-year PFS of FL patients on RB therapy was 70% (95% CI 75-99), on R-CHOP therapy - 44% (95% CI 73-90), on R-CHOP + HDT and autoSCT - 74% (95% CI 57-100), on R-CHOP + HDT without autoSCT - 80%. Conclusion. The R-B is most effective in FL 1 and 2 cytological types. The cytological type does not correspond to the type of tumor growth: at 3A and 3A + 3B cytological types, nodular / nodular - diffuse and diffuse types of growth are found. When choosing an induction course, one should look at the cytological type of FL. A high proliferative activity index (according to Ki67) is a predictor of resistance to R-B therapy. The absence of an interfollicular T-cell reaction in tumor tissue FL is associated with tumor chemoresistance. The presence of the bulky factor is associated (in most patients) with the FLIPI index with values from 3 to 5, and is a predictor of a poor response to therapy. Patients with bulky, high (more than 35%) Ki67 index and FLIPI from 3 to 5 in the debut of the disease as the first line therapy, it is preferable to choose the R-CHOP mode, and in the absence of (after 4-6 courses) to complete or partial remission to continue conducting the HDT.

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Section: Discussionunclassified

“…R-CHOP+ ВХТ и аутоТСКК. Двадцати одному пациенту после курсов R-CHOP продолжена (в связи с недостаточным противоопухолевым ответом) [15,16] терапия по протоколу последовательной ВХТ и выполнена аутоТСКК.…”

Section: R-bunclassified

Follicular lymphoma: first - line selection criteria of treatment

Nesterova¹,

Кравченко²,

Kovrigina³

et al. 2019

Terapevticheskii arkhiv

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“…По результатам ряда исследований точность МРТ-ДВИ-ВТ при оценке объема опухолевого поражения при ФЛ превышает 95% [8,9,15]. Поскольку инфильтрация костного мозга наблюдается у большинства (около 80%) больных ФЛ [18][19][20][21], проведение трепанобиопсии костного мозга (с последующим его гистологическим изучением) при ФЛ обязательно. В настоящее время эффективность МРТ-ДВИ-ВТ в выявлении специфического поражения костного мозга (даже при минимальной его вовлеченности) при ФЛ доказана [8,9,15,22].…”

Section: Abstract: Follicular Lymphoma Diffusion Wb-mri Pet Bone Munclassified

“…В ряде клинических исследований динамика объема опухоли имеет принципиальное значение в выборе тактики терапии [10,12,[18][19][20][21]. ПЭТ/КТ, МРТ и КТ в большинстве исследовательских центров в рутинной практике не определяют истинный объем опухоли (ограничивают технические сложности -наличие соответствующего программного обеспечения, а также трудоемкость процесса).…”

Section: çàêëþ÷åíèåunclassified

Informativeness of whole-body diffusion-weighted magnetic resonance imaging and positron emission tomography with computed tomography in follicular lymphoma

Nesterova¹,

Shutova²,

Луцик³

et al. 2020

Terapevticheskii arkhiv

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Aim.This study conducted the possibilities of diffusion-weighted magnetic resonance imaging of the whole body diffusion WB-MRI (in comparison with positron emission tomography with computed tomography PET/CT) in assessing the volume and prevalence of the tumor, as well as determining bone marrow (BM) damage (for various cytological types) in the diagnosis and staging of the disease in patients with FL. Materials and methods.A prospective comparative search study included 15 patients (4 men and 11 women, with a median age of 53 years) with newly diagnosed FL. Patients have not received antitumor chemotherapy previously. After the diagnosis was established, all patients (with the blindness of both the cases themselves and some specialists regarding the results of other specialists) were examined by PET/CT and diffusion WB-MRI, after which a BM examination was performed (histological examination and determination of B-cell clonality in BM puncture by PCR). Using the diffusion WB-MRI method, the prevalence of tumor lesion (nodal and extranodal foci) in each patient was estimated, and the total tumor volume was calculated, BM lesion was detected, and BM lesion volume was calculated. For lesions of different localization, the measured diffusion coefficient (DC) of the diffusion WB-MRI and the standardized rate of accumulation of the radiopharmaceutical in tissues (SUV) of the PET/CT method were determined and compared with each other (for the same areas). Statistical analysis was performed using the estimate of agreement (by Cohens kappa coefficient and asymptotic test) of the results of the compared methods. Results.Estimates of the prevalence of tumor damage (lymph nodes and extranodal foci) using the diffusion WB-MRI and PET/CT methods were the same. High DC and SUV were observed in the peripheral lymph nodes, extranodal foci and bulky, low DC and SUV in the foci of BM. All 4 methods successfully determined BM damage, however, the diffusion WB-MRI had comparatively less negative results. The highest values of SUV and CD were noted in cases of the 3 grade of FL. Using the diffusion WB-MRI method, the prevalence of tumor lesion was assessed in each patient (nodal and extranodal foci were detected) and the total tumor volume was calculated, BM lesion detection was performed, and the volume of BM lesion was calculated. It is important to note that with the help of diffusion WB-MRI, it was possible to measure separately the total tumor volume (462025 cm3) and separately the volume of bulky (251358 cm3). The diffusion WB-MRI allowed us to differentiate the volume of tumor tissue (reduced as a result of treatment) and residual (fibrous-adipose) tissue in residual formations (which averaged 21% of the initial volume). The predictors of a poor antitumor response were the maximum SUV values (more than 14.0) and the minimum DC values (0.510-3mm2/s) in the BM foci. Conclusion.The diffusion WB-MRI allows for detailed visualization of BM lesions and surrounding soft tissues both in the debut of the FL and in the process of tracking the effectiveness of chemotherapy, which makes it possible to use it along with PET/CT. Diffusion WB-MRI allows to separately evaluate the volume of true tumor tissue and residual tissue. Cases of the 3 grade of FL (including the transformation of FL into diffuse B-large cell lymphoma) are isolated due to low DC values (and high SUV values) in the tumor tissue. BM foci of FL lesion also have (in comparison with nodal and extranodal foci) lower DC values. The predictors of a poor antitumor response were high (from 14.0 or more) SUV valuesin the tumor (and especially in bulky), and low (about 0.5103mm2/s) DC values of BM foci. The PET/CT and diffusion WB-MRI have proven to be reliable diagnostic tools for establishing the stage of FL and detecting BM damage. Diffusion WB-MRI for FL is an informative first-line diagnostic method that allows regular monitoring of the disease and early detection of foci of relapse and disease progression.

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Follicular lymphoma: results of multicenter study of first-line therapy with bendamustine and rituximab, risk factors for adverse events (fl-rus-2013 protocol)

et al. 2018

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Follicular lymphoma. High-dose immunochemotherapy with autologous blood stem cell transplantation: Results of the first prospective study in Russia

Abstract: The first prospective study of intensive therapy for FL in Russia has demonstrated that HDCT with further auto-BSCT in first-line therapy allows complete remission in patients with poor prognostic factors and higher overall and progression-free survival rates.

Cited by 6 publications

References 27 publications

Follicular lymphoma: first - line selection criteria of treatment

Follicular lymphoma: first - line selection criteria of treatment

Informativeness of whole-body diffusion-weighted magnetic resonance imaging and positron emission tomography with computed tomography in follicular lymphoma

Follicular lymphoma: results of multicenter study of first-line therapy with bendamustine and rituximab, risk factors for adverse events (fl-rus-2013 protocol)

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