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.

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.

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)

Risk Factors for Response after Initial Therapy for Acute Graft-Versus-Host-Disease (aGVHD).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5015-5015
Author(s):  
Jason R. Westin ◽  
Rima M. Saliba ◽  
Marcos de Lima ◽  
Amin Alousi ◽  
Chitra Hosing ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Response Rate ◽  
Initial Therapy ◽  
Independent Effect ◽  
P Value ◽  
First Line ◽  
Overall Response ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade Iii

Abstract Introduction: Acute GVHD remains the most important early complication and limitation to allogeneic hematopoietic stem cell transplantation (HSCT). Although far from optimal, corticosteroids remain initial standard therapy with an overall response rate of 50%. Steroid resistant patients have a dismal prognosis, with mortality rates reaching 90%. Objective: To identify the subgroup of patients that would not benefit from initial therapy with corticosteroids. Thus, accrual of these patients into clinical studies would be mandatory. Methods: Retrospective evaluation of all (N= 287) patients who developed biopsy proven aGVHD after allogeneic HSCT at the University of Texas M. D. Anderson Cancer Center from 1998 through 2002. All patients received initial therapy for aGVHD with methylprednisolone. Prognostic factors for response (CR/PR) to initial therapy with corticosteroids were evaluated using logistic regression analysis including age, gender, donor/patient sex mismatch (F/M), donor type, cell type, intensity of conditioning regimen, diagnosis, disease status at transplant, number of prior chemotherapy regimens, number of prior autologous HSCT, CD34+ cell dose infused, time of onset of aGVHD and grade at initiation of first line therapy. Results: At the time of first line therapy, 89/287 patients (31%) had grade I aGVHD, 141 (49%) had grade II, and 57 (20%) had grade III–IV. Overall response to first line therapy was 56% and was comparable between patients with grade I and II aGVHD. Grade III–IV aGVHD (CR/PR 39% vs. 60%, p=0.003) and hyperacute GVHD (occurring by day +14) (CR/PR 42% vs. 61%, p=0.007) were the most significant prognostic factors for failure. Sex mismatch was associated with significantly lower response rate in patients with grade III–IV (CR/PR 12% vs. 49%, p=0.02) but not in patients with grade I–II (CR/PR 61% vs. 60%, p=0.9). Failure to respond to first line therapy was the most significant predictor of non-relapse mortality at one and two years after initiation of first line therapy (p<0.001) for all GVHD grades. Conclusions: Hyperacute GVHD and sex mismatch are significant predictors of response to first line therapy. Response to first line therapy has a strong and independent effect on survival. These factors should be integrated in prognostic scoring systems of aGVHD, which would allow identification of patients who would not benefit from standard therapeutic approaches. Response To First Line Therapy Overall (N=287) n %CR/PR p value CR: complete remission, PR: partial remission Grade at First Line I 89 65% Reference II 141 57% 0.2 III/IV 57 39% 0.003 Grade I/II (N=230) Grade III/IV(N=57) n, %CR/PR p value n, %CR/PR p value Hyperacute GVHD Yes 73 42% 60, 48% 13, 15% No 214 61% 0.007 170, 65% 0.03 44, 45% 0.05 Donor/Patient sex mismatch Yes 73 51% 57, 61% 16, 12% No 214 58% 0.3 173, 60% 0.9 41, 49% 0.02

scholarly journals The Optimal First-Line Therapy ofHelicobacter pyloriInfection in Year 2012

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Chao-Hung Kuo ◽  
Fu-Chen Kuo ◽  
Huang-Ming Hu ◽  
Chung-Jung Liu ◽  
Sophie S. W. Wang ◽  
...  
Keyword(s):  
Rescue Therapy ◽  
Treatment Strategies ◽  
Sequential Therapy ◽  
Antibiotics Resistance ◽  
First Line ◽  
First Line Therapy ◽  
Metronidazole Resistance ◽  
Rescue Treatment ◽  
New Treatment ◽  
H Pylori

This paper reviews the literature about first-line therapies forH. pyloriinfection in recent years. First-line therapies are facing a challenge because of increasing treatment failure due to elevated antibiotics resistance. Several new treatment strategies that recently emerged to overcome antibiotic resistance have been surveyed. Alternative first-line therapies include bismuth-containing quadruple therapy, sequential therapy, concomitant therapy, and hybrid therapy. Levofloxacin-based therapy shows impressive efficacy but might be employed as rescue treatment due to rapidly raising resistance. Rifabutin-based therapy is also regarded as a rescue therapy. Several factors including antibiotics resistance, patient compliance, and CYP 2C19 genotypes could influence the outcome. Clinicians should use antibiotics according to local reports. It is recommended that triple therapy should not be used in areas with high clarithromycin resistance or dual clarithromycin and metronidazole resistance.

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.

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

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.

Reversal of Resistance to Doxifluridine and Fluorouracil in Metastatic Colorectal Cancer: The Role of High-Dose Folinic Acid

1992 ◽  
Vol 78 (4) ◽  
pp. 258-261 ◽  
Author(s):  
Marco Colleoni ◽  
Emilio Bajetta ◽  
Filippo de Braud ◽  
Nicoletta Zilembo ◽  
Franco Noiè ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Folinic Acid ◽  
Performance Status ◽  
Objective Response ◽  
High Dose ◽  
Severe Toxicity ◽  
First Line ◽  
First Line Therapy ◽  
Colon And Rectum

The benefits from medical treatment in colorectal cancer are limited. Fluorouracil remains the only recognized drug, and how to treat unresponsive patients is still debated. To evaluate the role of folinic acid (FA) in circumvence resistance in colorectal cancer, 28 patients pretreated with fluoropyrimidine were candidated to receive one of the following schedules: fluorouracil (600 mg/m2) associated with FA (500 mg/m2) weekly for 6 weeks (Regimen A: 21 cases), or fluorouracil (370 mg/m2) plus FA (200 mg/m2) dally for 5 days every 4 weeks (Regimen B: 7 cases). Fourteen patients were pretreated with doxifluridlne, a new fluoropyrimldine derivative with a peculiar mechanism of action, and the remaining 14 patients with fluorouracil. All but 2 patients were unresponsive to first-line treatments. When the treatment began, the median age of the patients was 60 years (range, 30-68). The performance status (ECOG) was 0/1 in 25 of them, and the primary tumor was in the colon and rectum in 19 and 9 patients, respectively. Sites of disease were liver (64 %), lung (35 %), local recurrence (10 %) and peritoneum (10 %). A median of 3 cycles (range, 1-7) was delivered, and no objective response was observed in the group of patients pretreated with doxlfluridine or in the group pretreated with fluorouracil. In 5 cases a significant decrease in baseline CEA values was observed. Therapy was well tolerated, and no grade 4 toxicity was encountered. Severe toxicity was limited and included diarrhea (7 patients), stomatitis (1 patient) and nausea/vomiting (1 patient). High-dose FA has no role in reversing resistance to fluoropyrimidine, and other mechanisms of refractoriness are surely involved. FA should be associated with fluoropyrimidine as first-line therapy together with other biochemical modulators. Further rescue therapies need to be developed.

Procarbazine and High-Dose Tamoxifen as a Second-Line Regimen in Recurrent High-Grade Gliomas: A Phase II Study

1999 ◽  
Vol 17 (2) ◽  
pp. 645-645 ◽  
Author(s):  
Alba A. Brandes ◽  
Mario Ermani ◽  
Sergio Turazzi ◽  
Elvira Scelzi ◽  
Franco Berti ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Chemotherapy Regimen ◽  
Phase Ii Study ◽  
Tumor Control ◽  
High Dose ◽  
High Grade ◽  
Second Line ◽  
First Line ◽  
High Grade Gliomas

PURPOSE: A phase II study was conducted in patients with high-grade gliomas that recurred after surgery plus radiotherapy and a first-line nitrosourea-based regimen. Our aim was to investigate the efficacy of procarbazine (PCB) combined with high-dose tamoxifen in relation to tumor control, toxicity, and time to progression (TTP). PATIENTS AND METHODS: Fifty-three patients were treated with procarbazine in repeated 30-day courses at 100 mg/m2/d plus tamoxifen 100 mg/d, with a 30-day interval between courses. Thirty-four patients had been pretreated with a first-line nitrosourea-based chemotherapy regimen (group A), and 19 patients had also been pretreated with a second-line chemotherapy regimen consisting of carboplatin and teniposide (group B). Twenty-one of the patients had also been procarbazine pretreated, whereas the remaining 32 patients were not procarbazine pretreated. RESULTS: The response was assessed in 51 patients, 28 of whom had glioblastoma multiforme (GBM) and 23 of whom had anaplastic astrocytoma (AA). There were two complete responses (CR) (4%) and 13 partial responses (PR) (25.5%). The overall response rate (CR + PR) was 29.5% (SE, 6.4; 95% confidence interval [CI], 23 to 35.8). Seventeen patients (32%) had stable disease (SE, 6.2; 95% CI, 21 to 33.6). The median TTP was 13 weeks for patients with GBM and 33 weeks for patients with AA (P = .006). The median survival time (MST) was 27 weeks for patients with GBM and 57 weeks for those with AA (P = .006). CONCLUSION: Combined PCB and tamoxifen as a second-line regimen gave a reasonably high response rate in patients with heavily pretreated high-grade gliomas. However, although it resulted in an improvement in the patients' quality of life and/or performance status, it was not followed by an increased TTP or MST.

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