Effectiveness of high-dose combination chemotherapy and autologous bone marrow transplantation for patients with non-Hodgkin's lymphomas who are still responsive to conventional-dose therapy.

1989 ◽  
Vol 7 (11) ◽  
pp. 1621-1629 ◽  
Author(s):  
J G Gribben ◽  
A H Goldstone ◽  
D C Linch ◽  
G Taghipour ◽  
A K McMillan ◽  
...  
Keyword(s):  
Combination Chemotherapy ◽  
Response Rate ◽  
Autologous Bone Marrow ◽  
High Dose ◽  
First Line ◽  
First Line Therapy ◽  
Conventional Dose ◽  
Line Therapy ◽  
Dose Combination ◽  
Hodgkin's Lymphomas

We commenced a study in September 1981 to investigate the role of high-dose combination chemotherapy in the management of patients with non-Hodgkin's lymphomas who had failed conventional therapy. Fifty patients with diffuse intermediate- and high-grade non-Hodgkin's lymphomas were treated with high-dose combination chemotherapy with autologous bone marrow rescue (ABMT) and have a minimum follow-up of 1 year. Twenty patients had disease that was still responsive to conventional-dose chemotherapy, 15 had achieved a partial response (PR) to first-line therapy, and five were showing PR to salvage therapy after relapse. Twelve of these patients (60%) achieved complete remission (CR) (two following boost radiotherapy) and three patients have nonprogressive masses on computed tomographic (CT) scan as the only abnormality. None of these patients died during the procedure. Twenty-nine patients had disease not responsive to chemotherapy at conventional dosages: 19 had no response to first-line therapy and 10 showed no response to salvage therapy given after relapse. Only three of these patients achieved CR, all of short duration only. Only two patients in this group remain alive more than 2 years after the procedure and both have nonprogressive abnormalities on CT scan. Nine patients (31%) died of sepsis during the procedure. In those patients with disease not responsive to conventional-dose therapy, dose escalation is associated with a high procedure-related mortality and a low response rate. In those patients who still have chemotherapy-responsive disease the response rate is high and mortality is low.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary Female Genital Lymphoma: Prognostic and Therapeutic Considerations

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4941-4941
Author(s):  
Sara Steffanoni ◽  
Alberto Agazzi ◽  
Daniele Laszlo ◽  
Sarah Jane Liptrott ◽  
Mara Negri ◽  
...  
Keyword(s):  
Response Rate ◽  
Early Stage ◽  
Local Treatment ◽  
High Dose ◽  
First Line ◽  
Bulky Disease ◽  
First Line Therapy ◽  
Line Therapy ◽  
Female Genital

Abstract Primary Female Genital Lymphoma (PFGL) is very rare, representing 1.5% of all Non-Hodgkin’s Lymphomas (NHLs) and 0.5% of female genital malignant tumours; uterus is the main commonly genital site involved by NHL. Most PFGLs are B-cell lymphomas; usually they occur in 5th decade of life. Because of PFGL rarity, a standard treatment has not been identified yet. This is a retrospective study on 20 women with PFGL, treated at European Institute of Oncology. The median age was 52 yrs (range 30–79 yrs); at diagnosis 6 pts were asymptomatic, 11 reported pelvic symptoms and 3 B symptoms. According to the International Prognostic Index, 7 pts had low, 6 intermediate, 6 high risk and one pt not known. Eleven pts had uterine involvement, with a concomitant extension to vagina in 5 of them, ovary NHL was recognised in 4 pts, vaginal NHL in 4 pts and vulvar NHL in one pt. Diffuse large B-cell NHL (DLBCL) was diagnosed in 14 pts, marginal extranodal NHL in 3 pts and follicular in 3 pts. According to Ann Arbor staging system: 8 pts were in early stage (IE–IIE) and 12 pts in stage IVE; considering FIGO system: 11 pts were in early stage (I–II), 6 pts in stage III for regional lymph node involvement and 3 in stage IV for concomitant non-genital extranodal localization; 12 pts presented with bulky disease. At diagnosis no pts had bone marrow involvement. The diagnostic biopsy was performed by endoscopy in 13 pts and by ultrasound-guided in 2 pts, whereas 5 pts underwent laparotomy. One pt with vulva-limited marginal NHL did not receive any treatment until disease progression (PD) and transformation to DLBCL. Five pts underwent laparotomy and adjuvant chemotherapy (CT) alone (n=4) or in combination with radiotherapy (RT) (n=1); 14 pts received CT alone (n=8) or in combination with RT (n=6) as first line therapy. Anthracycline-containing CT was delivered to all pts with DLBCL (n=14) and to one pt with high grade follicular NHL, 12 of them received concurrent immunotherapy anti-CD20 (Rituximab). Central nervous system (CNS) chemo-prophylaxis with i.v. high dose methotrexate was delivered to 3 pts because of advanced or bulky disease. Two pts with follicular and 2 with marginal subtype received alkylating-containing CT alone (n=2) or with Rituximab (n=2). The Overall Response Rate (ORR) to first line therapy was 80%; the response did not improve by the addition of local treatment to CT. Three pts did not response to first line therapy: one with marginal NHL in stable disease did not receive any additional treatment because of asymptomatic disease; two with DLBCL in PD underwent salvage treatment with high dose CT and died in PD, concurrent intrathecal therapy was mandatory in one pt because of CNS relapse. Three pts with follicular NHL, in response to first line therapy, relapsed: one went on to receive maintenance Rituximab, one resulted refractory to different rescue CT regimens and died in PD, one underwent autologous bone marrow transplantation obtaining CR. After a median follow up of 51 months (range 11–164 months), 17 pts are still alive: 10 in CR and 7 in PR, 3 pts died in PD. The Overall Survival (OS) at 3 and 14 yrs was 84.8% and 42.4% respectively. According to the literature the most common histological subtype of PFGL occurred in our population was DLBCL and the most frequent genital site involved was uterus (55% of cases) [Lagoo et al. 2006]. An additional local treatment did not seem to give an advantage in terms of ORR, PFS and OS in comparison with systemic therapy alone, as stated by the literature [Signorelli et al. 2006]. Concerning the pts treated with anthracycline-containing CT with or without Rituximab (n=15), 8 pts (53%) and 5 pts (33%) achieved CR and PR respectively, 2 pts (13%) had a PD during treatment, only one pt in CR relapsed after 65 months from the first line therapy. After a median follow up of 27 months 12 pts (80%) are alive, 3 (20%) died in PD. The Response Rate and OS in the subgroup of pts that received anthracycline-containing CT resulted similar to those reported in the literature [Coiffier 2002]; therefore female genital involvement by NHL doesn’t seem to represent a negative prognostic factor.

High-dose carboplatin, etoposide, and cyclophosphamide with autologous bone marrow transplantation in first-line therapy for patients with poor-risk germ cell tumors.

1997 ◽  
Vol 15 (7) ◽  
pp. 2546-2552 ◽  
Author(s):  
R J Motzer ◽  
M Mazumdar ◽  
D F Bajorin ◽  
G J Bosl ◽  
P Lyn ◽  
...  
Keyword(s):  
Autologous Bone Marrow Transplantation ◽  
Germ Cell Tumors ◽  
Autologous Bone Marrow ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
First Line ◽  
Poor Risk ◽  
First Line Therapy ◽  
Line Therapy ◽  
Autologous Bone

PURPOSE A treatment program that included high-dose carboplatin, etoposide, and cyclophosphamide (CEC) followed by autologous bone marrow transplantation (AuBMT) was investigated as first-line therapy in patients with poor-risk germ cell tumors (GCTs). PATIENTS AND METHODS Previously untreated GCT patients with poor-risk features were treated with etoposide, ifosfamide, and cisplatin (VIP) with or without high-dose CEC plus AuBMT. Patients qualified for a change to high-dose CEC if a prolonged clearance of elevated serum tumor markers was observed after two cycles of the cisplatin-containing regimen. RESULTS Sixteen patients were treated with VIP alone and 14 with VIP and high-dose CEC. Seventeen patients (57%) achieved a complete response. Twenty are alive (67%) and 15 (50%) are free of disease at a median follow-up time of 30 months. For 23 cycles of high-dose CEC, the median time from AuBMT to a granulocyte count > or = 0.5/microL was 11 days (range, 0 to 14) and to a platelet count 50,000/microL, 19 days (range, 14 to 34). The survival of 58 patients treated in two of our center's programs that incorporated high-dose chemotherapy (high-dose carboplatin plus etoposide [CE] and CEC) was compared with our prior experience with conventional-dose cisplatin chemotherapy alone in poor-risk GCT. Patients treated with marker-dependent, early-intervention high-dose chemotherapy experienced longer survival (P = .001). CONCLUSION In this setting, high-dose CEC was well tolerated, cumulative toxicity was lacking, and the recovery of blood counts after AuBMT was rapid. A randomized trial has been initiated to investigate further the role of high-dose CEC in first-line therapy for patients with poor-risk GCT.

Association between Platelet-Associated Immunoglobulin G Levels and Response to Corticosteroid Therapy in Patients with Newly Diagnosed Immune Thrombocytopenia

2020 ◽  
pp. 1-6
Author(s):  
Masuho Saburi ◽  
Masao Ogata ◽  
Yasuhiro Soga ◽  
Takako Satou ◽  
Kazuhito Itani ◽  
...  
Keyword(s):  
Corticosteroid Therapy ◽  
Immunoglobulin G ◽  
Immune Thrombocytopenia ◽  
High Dose ◽  
First Line ◽  
Laboratory Findings ◽  
Platelet Production ◽  
First Line Therapy ◽  
Line Therapy ◽  
Immature Platelet Fraction

<b><i>Objective:</i></b> Platelet-associated immunoglobulin G (PA-IgG) refers to IgG attached to the surface of platelets, while the immature platelet fraction (IPF) reflects the state of platelet production in bone marrow. Since PA-IgG and IPF are increased in patients with immune thrombocytopenia (ITP), reflecting amounts of platelet antibodies and compensatory platelet production, respectively, we hypothesized that these laboratory findings may provide useful markers for predicting treatment response in patients with ITP. We therefore retrospectively investigated associations between levels of these markers at diagnosis and response to first-line therapy in patients with ITP. <b><i>Methods:</i></b> Forty-three patients diagnosed with ITP at Oita Kouseiren Tsurumi Hospital between May 2010 and November 2018 were included. Patients were divided into 2 groups based on response to corticosteroid as first-line therapy. Laboratory findings were compared between responders and nonresponders. <b><i>Results:</i></b> Median PA-IgG was 285 ng/10<sup>7</sup> cells (range, 45.5–18,200 ng/10<sup>7</sup> cells), and median IPF was 15.5% (range, 5.4–62.1%). Median levels were higher than the respective upper limits of normal range (PA-IgG, 0–46 ng/10<sup>7</sup> cells; IPF, 1.1–9.5%). First-line therapy was performed using standard-dose prednisolone (0.5–1.0 mg/kg/day) in 32 patients and high-dose dexamethasone (40 mg/day, 4 days) or methylprednisolone (125–1,000 mg/day, 3–4 days) in 11 patients. Twenty-four patients (55.8%) responded to first-line therapy. In univariate analysis, type of corticosteroid (<i>p</i> = 0.17) tended to differ between groups but did not differ significantly, and no difference in IPF level was apparent between responders (15.35%; range, 5.4–41.5%) and nonresponders (16.7%; range, 6.3–62.1%; <i>p</i> = 0.15). PA-IgG was significantly higher among nonresponders (430 ng/10<sup>7</sup> cells; range, 101–18,200 ng/10<sup>7</sup> cells) than among responders (254.5 ng/10<sup>7</sup> cells; range, 45.5–470 ng/10<sup>7</sup> cells; <i>p</i> = 0.004). Multivariate analysis revealed PA-IgG was independently associated with response to first-line therapy (odds ratio, 1.000; 95% confidence interval, 1.000–1.010; <i>p</i> = 0.029). <b><i>Conclusion:</i></b> Our data suggested that PA-IgG at diagnosis could offer a useful predictor of response to first-line corticosteroid therapy for ITP.

scholarly journals The first-line therapy of aggressive non-Hodgkin’s lymphomas in russian clinical practice: data from the EQUILIBRIUM study

2020 ◽  
Vol 15 (2) ◽  
pp. 10-18
Author(s):  
L. G. Babicheva ◽  
I. V. Poddubnaya
Keyword(s):  
Overall Survival ◽  
Clinical Practice ◽  
Complete Remission ◽  
B Cell ◽  
Long Term Results ◽  
First Line ◽  
Therapy Efficacy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Hodgkin's Lymphomas

The objective: evaluation of effectiveness of the first-line therapy with rituximab of B-cell lymphoproliferative diseases in Russian clinical practice in the period from 2014 to 2017.Materials and methods. The EQUILIBRIUM post-registration multicenter study included 1000 patients aged 21 to 91 years old with a verified diagnosis of B-cell non-Hodgkin’s lymphoma, or chronic lymphocytic leukemia, who received at least 4 cycles of rituximab-containing therapy with Acellbia®. The group of aggressive non-Hodgkin’s lymphomas (aNHL), which is the subject of this article, included 295 patients with a median age of 55.9 years: diffuse B-large cell lymphoma – 87 %, primary mediastinal lymphoma – 11 %, Burkitt’s lymphoma – 1 %. Group characterized by the presence of aggressive clinical signs reflecting the poor prognosis: in the majority of patients, generalized stages were diagnosed (61 %), in half of the cases (50.2 %), extranodal localization of tumor foci was detected (in 32.4 % of patients there were 2 or more). The overwhelming majority of patients (84.5 %) received adequate treatment complying with national and international recommendations (R-CHOP, R-CHOEP and R-EPOCH, high-intensity NHL-BFM-R, R-HyperCVAD and R-MACOP-B regimes). The use of R-CVP, FCR, RB, Chl-R, R-monotherapy treatment programs (which received 15.5 % of patients) was considered inadequate for this category of patients.Results. According to the results of the final assessment, high therapy efficacy was established: the overall response exceeded 90 %, complete remission was achieved in most patients with aNHL (68.5 %), partial remission – in every 5th patient (21.8 %). With a median follow-up of 15 months, 16 (5.42 %) deaths and 34 (11.53 %) events were registered. Median of event-free survival and overall survival have not been achieved. Statistically significant differences depending on first-line therapy efficacy were found in overall survival (p = 0.00000) and eventfree survival (p = 0.00000), once again confirming that the main goal of aNHL treatment is to achieve complete remission.Conclusion. Available and compliant with national clinical guidelines treatment of aNHL patients with Russian bioanalogue of anti-CD20 monoclonal antibodies (Acellbia®) demonstrates high immediate efficacy and acceptable long-term results, comparable to a retrospective analysis of previous clinical studies of the original drug rituximab.

High-dose, single-agent irinotecan as first-line therapy in the treatment of metastatic colorectal cancer

2002 ◽  
Vol 50 (5) ◽  
pp. 383-391 ◽  
Author(s):  
Ychou M. ◽  
Raoul J. ◽  
Desseigne F. ◽  
Borel C. ◽  
Caroli-Bosc F. ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Single Agent ◽  
High Dose ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Management of refractory myeloma: a review.

1988 ◽  
Vol 6 (5) ◽  
pp. 889-905 ◽  
Author(s):  
A C Buzaid ◽  
B G Durie
Keyword(s):  
Protein Concentration ◽  
Response Rate ◽  
Clinical Problem ◽  
Initial Therapy ◽  
M Protein ◽  
Treatment Modalities ◽  
High Dose ◽  
First Line ◽  
First Line Therapy ◽  
New Treatment

Management of refractory myeloma represents a common and challenging clinical problem. Approximately 30% to 50% of patients with multiple myeloma do not respond to first-line therapy, and those who initially achieve a remission will eventually relapse. Surprisingly, there is no routinely accepted approach to patients with refractory disease. Therefore, we review the literature in an attempt to provide an overview of the published results and outline our treatment recommendations for such patients. We suggest the following: (1) for truly resistant patients (ie, those who clearly progress with initial therapy), administration of high-dose or pulsed glucocorticosteroids is the best treatment, with an expected response of 40% (defined as a greater than or equal to 50% reduction in monoclonal [M]-protein concentration); (2) for patients who relapse during therapy or relapse within 6 months of stopping the initial treatment, the VAD regimen (vincristine, doxorubicin, and dexamethasone) is one of the most effective salvage therapies, resulting in an approximately 75% response rate (greater than or equal to 50% reduction in M-protein concentration); (3) for patients who relapse within more than 6 months of stopping therapy (unmaintained remission), reinitiation of the initial therapy represents an excellent alternative, leading to recontrol in 60% to 70% of patients (greater than or equal to 50% reduction in M-protein concentration). If progression is observed or if there is response and then relapse in this setting, VAD chemotherapy can be administered again. (4) Patients who fail second-line salvage therapies should enter well-designed clinical trials to evaluate new treatment modalities. If this is not feasible, alpha-interferon or "systemic" radiotherapy are recommended in selected cases.

scholarly journals A randomized phase 3 trial of auto vs. allo transplantation as part of first-line therapy in poor-risk peripheral T-NHL

Blood ◽  
2020 ◽  
Author(s):  
Norbert Schmitz ◽  
Lorenz H Truemper ◽  
Krimo Bouabdallah ◽  
Marita Ziepert ◽  
Mathieu Leclerc ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Allogeneic Transplantation ◽  
T Cell Lymphoma ◽  
High Dose ◽  
First Line ◽  
High Dose Therapy ◽  
Peripheral T Cell Lymphoma ◽  
First Line Therapy ◽  
Line Therapy

Standard first-line therapy for younger patients with peripheral T-cell lymphoma consists of six courses of CHOP or CHOEP consolidated by high-dose therapy and autologous stem cell transplantation (AutoSCT). We hypothesized that consolidative allogeneic transplantation (AlloSCT) could improve outcome. 104 patients with nodal peripheral T-cell lymphoma except ALK+ ALCL, 18 to 60 years of age, all stages and IPI scores except stage 1 and aaIPI 0, were randomized to receive 4 x CHOEP and 1 x DHAP followed by high-dose therapy and AutoSCT or myeloablative conditioning and AlloSCT. The primary endpoint was event-free survival (EFS) at three years. After a median follow-up of 42 months, 3-year EFS of patients undergoing AlloSCT was 43% (95% confidence interval [CI]: 29%; 57%) as compared to 38% (95% CI: 25%; 52%) after AutoSCT. Overall survival at 3 years was 57% (95% CI: 43%; 71%) versus 70% (95% CI: 57%; 82%) after AlloSCT or AutoSCT, without significant differences between treatment arms. None of 21 responding patients proceeding to AlloSCT as opposed to 13 of 36 patients (36%) proceeding to AutoSCT relapsed. Eight of 26 patients (31%) and none of 41 patients died due to transplant-related toxicity after allogeneic and autologous transplantation, respectively. In younger patients with T-cell lymphoma standard chemotherapy consolidated by autologous or allogeneic transplantation results in comparable survival. The strong graft-versus-lymphoma effect after AlloSCT was counterbalanced by transplant-related mortality. CHO(E)P followed by AutoSCT remains the preferred treatment option for transplant-eligible patients. AlloSCT is the treatment of choice for relapsing patients also after AutoSCT.

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