Refractoriness to transfusions of platelet concentrates (PC) adversely affects the conduct of complex therapy in hematological patients. Individual selection of platelets is recommended for such patients. In cases of high degree of alloimmunization with the formation of polyspecific antibodies, when individual selection is difficult, procedures plasmapheresis (PPs) is included in the treatment program.Aims: to evaluate the effectiveness of PC transfusions by individual selection in patients refractory to transfusions and the use of PPs as a second line therapy in combination with individual platelet selection.Materials and methods: from September 2015 to December 2017, 91 patients with refractory to PC transfusions from 1263 patients who received PC transfusion were observed in the center’s clinics. The median age was 43 (18–71) years. M/F – 38/53. Patients: 20 – aplastic anemia (AA), 17 – myelodysplastic syndrome (MDS), 45 – acute myeloid leukemia (AML), 9 – acute lymphoblastic leukemia (ALL). All patients underwent PC transfusion by individual selection (HLA/HPA) Immucor’s Capture-P solid phase technology. In 28 (30 %) of 91 patients, due to the inability to select, there was a need for PP as a second line therapy. Patients: AA – 4 (20 %); MDS – 8 (47 %); AML – 12 (26 %); ALL– 4 (44 %). The median age was 48 (23–71) years. M/F – 8/20. From 2 to 15 procedures were performed (on average – 6) for each patient. All patients received PC transfusions by individual selection by cross-matching immediately after the PP procedure. The efficacy of PC transfusions was assessed by Absolute Platelet Increment (API) and Corrected Count Increment (CCI), relief of hemorrhagic syndrome.Results: in 26 of 28 refractory to PC transfusions patients, in the absence of compatible donor platelets, carrying out PPs in combination with subsequent individual platelet selection promoted relief of hemorrhagic syndrome, increase in API from 3.3 × 109/L at 29.5 × 109/L and CCI from 1.3 to 10.7. Against the background of PPs, combined with individual selection, the degree of alloimmunization (the percentage of incompatible pairs) decreased on average: AA (n = 4) – from 91.7 to 50.2 %; MDS (n = 8) – from 89.6 to 31.6 %; AML (n = 12) – 86.0 to 40.5 % and ALL (n = 4) – from 91.7 to 37.7 %. In 2 patients with a high degree of alloimmunization and after carrying out PPs, it was not possible to select compatible platelets, PC transfusions were ineffective (API = 5 × 109/L, CCI = 1), and hemorrhagic syndrome was not completely managed, but its severity was reduced.Conclusions. With the development of refractoriness to PC transfusions and the ineffectiveness of individual platelet selection, PPs should be used as the second line of therapy, which, combined with individual selection, increases the likelihood of compatible donor-recipient pairs and increases the clinical efficacy of PC transfusions. When PPs is ineffective in combination with individual selection, it is necessary to exclude the syndrome of increased consumption and other mechanisms of refractoriness.
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.
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.
Background: FL is one of the most frequent types of lymphomas: it consists about 22% of non-Hodgkin lymphomas in Russia. 20 % of pts have an aggressive tumor after standard therapy. In FL pts with unfavorable prognosis (FLIPI-1 III-IV, fast growth of tumor mass, B-symptoms, third cytological grade of tumor, bulky, absence of tumor response after first line R-CHOP-21 therapy) autoSCT allows to increase the overall (OS) and progression-free survival (PFS). Aim: To estimate an efficacy of HDT (high dose therapy) with following autoSCT in front-line therapy of FL pts with factors of poor prognosis. Patients and Methods: Since 2000 to 2015 years in National Research Center for Hematology were treated 39 FL pts with poor prognosis. All pts received R-CHOP-21 induction therapy. In 24 patients (62%) who hadn't partial response or poor prognosis patients with partial response after 4-6 courses autoSCT was performed. This group consists of 17 males and 7 females with median age 46 years old (31-68). Majority of pts (23/24) had IV stage of disease according to Ann Arbor. In 16/24 (66%) cases pts had bulky disease. 3/24 pts had phenomenon of leukaemization. Basing on FLIPI-1 criteria all pts were divided into 3 groups: low risk - 5/24, intermediate - 3/24, high - 16/24. B-symptoms were in majority of cases (18/24). 18/24 pts were diagnosed with I-II cytological grade of FL, 6/24 - III A/B. Basing on tumor growth pattern there was following ratio: nodular tumor growth revealed in 6/24 pts, nodular-diffuse tumor growth - in 15/24, diffuse tumor growth - in 3/24. Immunochemical analysis of serum and urine proteins was performed in 20/24 cases, among them increased level of serum β2-microglobulin was diagnosed in 10/20 pts. Increased activity of lactate dehydrogenase (LDH) was revealed in 16/24 pts. Bone marrow involvement at the time of disease onset was diagnosed in 18/24 pts. Results: After induction R-CHOP-21 chemotherapy pts underwent HDT which included two courses R-DHAP, following high-dose cyclophosphamide with rituximab, then high dose etoposide with rituximab. As condition regimen R-BEAM was performed. All 24 FL pts, who underwent autoSCT, continue to be in complete remission. Median follow-up was 31 months (7-178). Conclusions: Preliminary results of the first prospective study of intensive therapy of FL in Russia demonstrate that autoSCT in front line therapy provides to achieve a complete remission in pts with poor prognosis and allows to increase an overall and disease-free survival. Disclosures No relevant conflicts of interest to declare.
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