scholarly journals Primary Breast Double-hit Lymphoma Management and Outcomes: A Real-world Multicentre Experience

2021 ◽  
Author(s):  
Tingting Zhang ◽  
Yuanfeng Zhang ◽  
Hairong Fei ◽  
Xue Shi ◽  
Liang Wang ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Tumour Size ◽  
Treatment Options ◽  
Young Patients ◽  
Treatment Strategies ◽  
High Dose ◽  
Breast Irradiation ◽  
Treatment Regimens ◽  
Double Hit Lymphoma ◽  
Double Hit

Abstract Background: Primary breast double-hit lymphoma (PB-DHL) is a rare, highly aggressive malignancy that poses challenges regarding accurate diagnoses and selecting optimal treatment regimens. Methods: We retrospectively reviewed cases of patients diagnosed with PB-DHL in six academic centres between June 2014 and June 2020 in China. Study-specific data were recorded, including treatment options, therapeutic evaluation, prognostic factors and relapse patterns, and the overall survival (OS) and progression-free survival (PFS) were evaluated. Results: In total, 48 patients were enrolled, and the overall five-year OS and PFS rates were 41.7% (95% confidence interval [CI], 22.4–64.7%) and 37.5% (95% CI, 23.7–58.6%), respectively. Of the three treatment regimens, the five-year OS was higher in the dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R)/alternating with high-dose methotrexate and cytarabine (MA) group than in the DA-EPOCH-R or rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with cytarabine plus methotrexate (R-HyperCVAD) subgroups (57.1% vs. 38.9% vs. 31.3%; P = 0.016), as was the five-year PFS (50.0% vs. 38.9% vs. 25.0%; P = 0.038). Autologous stem cell transplantation (ASCT) prolonged the OS and PFS compared with non-ASCT patients (five-year OS: 72.2% vs. 23.3%; P < 0.001; five-year PFS: 72.2% vs. 16.7%, P < 0.001). Multivariate analysis identified tumour size, risk stratification, treatment with DA-EPOCH-R/MA, breast irradiation, and ASCT as significant prognostic factors. Conclusions: DA-EPOCH-R/MA is a promising regimen for PB-DHL, and breast irradiation yields complementary benefits for relapse reduction. ASCT significantly decreased disease relapse, providing a potential curative PB-DHL intervention and justifying ASCT as first-line therapy for young patients. More effective treatment strategies for PB-DHL patients remain encouraging.

scholarly journals Primary breast double-hit lymphoma management and outcomes: a real-world multicentre experience

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tingting Zhang ◽  
Yuanfeng Zhang ◽  
Hairong Fei ◽  
Xue Shi ◽  
Liang Wang ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Tumour Size ◽  
Treatment Options ◽  
Young Patients ◽  
Treatment Strategies ◽  
High Dose ◽  
Breast Irradiation ◽  
Treatment Regimens ◽  
Double Hit Lymphoma ◽  
Double Hit

Abstract Background Primary breast double-hit lymphoma (PB-DHL) is a rare, highly aggressive malignancy that poses challenges regarding accurate diagnosis and selecting optimal treatment regimens. Methods We retrospectively reviewed 48 cases of patients diagnosed with PB-DHL in six academic centres between June 2014 and June 2020 in China. Study-specific data were recorded, including treatment options, therapeutic evaluation, prognostic factors and relapse patterns, and the overall survival (OS) and progression-free survival (PFS) were evaluated. Results In total, 48 patients were enrolled, with 14 patients treated with DA-EPOCH-R/MA (rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, alternating with high-dose methotrexate and cytarabine), 18 patients treated with DA-EPOCH-R (rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), and 16 patients treated with R-HyperCVAD (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, alternating with cytarabine plus methotrexate). The overall 5-year OS and PFS rates were 41.7% (95% confidence interval [CI], 27.6–56.8%) and 37.5% (95% CI, 24.0–52.6%), respectively. Of the three treatment regimens, the 5-year OS was higher in DA-EPOCH-R/MA group than in the DA-EPOCH-R or R-HyperCVAD subgroups (57.1% vs. 38.9% vs. 31.3%; P = 0.016), as was the 5-year PFS (50.0% vs. 38.9% vs. 25.0%; P = 0.035). Autologous stem cell transplantation (ASCT) prolonged the OS and PFS compared with non-ASCT patients (5-year OS: 72.2% vs. 23.3%; P < 0.001; 5-year PFS: 72.2% vs. 16.7 %, P < 0.001). Multivariate analysis identified tumour size, risk stratification, treatment with DA-EPOCH-R/MA, breast irradiation, and ASCT as significant prognostic factors. Conclusions DA-EPOCH-R/MA is a promising regimen for PB-DHL, and breast irradiation yields complementary benefits for prognosis. ASCT significantly decreased disease relapse, providing a potential curative PB-DHL intervention and justifying ASCT as first-line therapy for young patients. More effective treatment strategies for PB-DHL patients remain encouraging.

Prognostic factors for response to second induction course in patients showing persistent disease after first course of standard induction chemotherapy for de novo acute myeloid leukemia (AML)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7056-7056
Author(s):  
J. Lee ◽  
S. Sym ◽  
S. Choi ◽  
J. Lee ◽  
Y. Lee ◽  
...  
Keyword(s):  
Risk Factors ◽  
Prognostic Factors ◽  
Induction Chemotherapy ◽  
De Novo ◽  
Chromosomal Abnormalities ◽  
Treatment Strategies ◽  
High Dose ◽  
Usual Practice ◽  
Persistent Disease ◽  
Resistant Disease

7056 Background: Standard induction chemotherapy for AML consists of cytarabine plus daunorubicin or idarubicin (‘7+3' regimen). For patients showing persistent leukemia after first induction course (IND1) of the induction, usual practice is to give a second course (IND2) of similar regimen (‘7+3' or 5+2'). This strategy, however, has not been well evaluated. We investigated prognostic factors for response to IND2. Methods: We performed a retrospective study in 110 patients with de novo AML. All patients received cytarabine (100 or 200 mg/m2/d) for 7 days plus daunorubicin (45–60 mg/m2/d) or idarubicin (12 mg/m2/d) for 3 days as IND1. Patients who showed persistent leukemia after IND1 were given the same doses and drugs as ‘5+2’ (n = 85) or ‘7+3’ (n = 25) for IND2. We collected the clinico-pathologic data of the patients at diagnosis and at IND2, and analyzed prognostic factors for response to IND2. Results: Sixty-one (55.5%) of 110 patients, who received IND2, achieved complete remission (CR). The causes of treatment failure were resistant disease in 35, complication of aplasia in 8, and indeterminated in 6. Five-year probabilities of overall and relapse-free survival were 25% and 21%, respectively. Multivariate analysis demonstrated that cellularity at interim BM biopsy > 30% (p = 0.015), blast percentage at interim BM aspiration > 30% (p = 0.031), presence of circulating blasts at IND2 (p = 0.011), and unfavorable chromosomal abnormalities (p = 0.014) were independent risk factors for failure to induce CR. The CR rates were significantly different according to the number of the risk factors: 73% for 0–1 factor, 48% for 2 factors, and 11% for 3–4 factors (p< 0.001). Conclusions: We identified 4 independent poor risk factors for CR in patients who showed persistent disease after standard induction chemotherapy and who received similar second induction course. Other treatment strategies such as high-dose cytarabine rather than standard regimens seem to be needed for the patients with 3–4 risk factors before IND2. No significant financial relationships to disclose.

ISS stage and network risk score to predict benefits of multiple myeloma treatment options.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20511-e20511
Author(s):  
Yu Liu ◽  
Li Wang ◽  
Haocheng Yu ◽  
Samir S. Parekh ◽  
Eric Schadt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Risk Score ◽  
Treatment Options ◽  
Young Patients ◽  
Stage I ◽  
Disease Stage ◽  
Cell Transplant ◽  
Treatment Regimens ◽  
Network Risk ◽  
The Impact

e20511 Background: Multiple myeloma (MM) is molecularly heterogeneous with many treatment regimens developed targeting different aspects of the disease. Multi-omics studies are now widely available, facilitating a precision medicine approach for personalized MM treatments. However, data from these studies vary with respect to treatment regimens, patient age, disease stage, and genomic alterations, thus complicating identification of treatment effects. Methods: From a Multiple Myeloma Molecular Causal Network (M3CN) model we previously described, we identified a prognostic subnetwork (prognNET) associated with survivals of newly diagnosed MM (NDMM) patients. We derived a network risk score (NRS) for each patient by inferring their molecular state with respect to prognNET, and partitioned patients into NRS low, medium, and high groups (referred as NRSL/M/H). We validated NRSL/M/H to be significantly associated with progression free survival (PFS) and overall survival (OS) in single variate and multi-variate Cox regression models including age and ISS stage in TT2,3,4 and HOVON studies. Results: To determine the impact of NRS in an independent contemporary dataset, we examined NDMM patients with RNAseq data in the MMRF-CoMMpass study. Among young patients (age < 65), ones with combined therapies (CoTs) as the first line therapy (n = 363) had better survival than ones on proteasome inhibitors (PIs) (n = 93) (p = 0.027 and 0.002 for PFS and OS). When stratified by ISS stage and NRS, there was no significant difference between CoTs and PIs except that in the stage I-NRSL group, patients on PIs had better PFS than ones on CoTs (p = 0.016). This suggests that NRS may be able to discriminate ISS stage I patients that do not need CoT. Similarly, we studied the ability of NRS to discriminate patients that benefit from autologous stem cell transplant (ASCT). In a model combining age, ISS stage, NSR, and induction treatment, ASCT was associated with better survival. When stratified young patients on CoTs by ISS stage and NRS, only the stage II-NRSM and stage III-NRSM patients benefited from ASCT in term of PFS (p = 0.01 and 0.005) and OS (p = 0.004 and 0.04). Conclusions: Stage and NRS group should be considered in personalizing treatment options for NDMM patients.

Clofarabine, Etoposide and Mitoxantrone In the Therapy of Relapsed and Refractory Acute Myelogenous Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4353-4353
Author(s):  
W. Christopher Ehmann ◽  
Sulfikar Ibrahim ◽  
Witold Rybka ◽  
David F. Claxton
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Treatment Options ◽  
Single Agent ◽  
Myelogenous Leukemia ◽  
Dose Finding ◽  
High Dose ◽  
Phase 2 ◽  
Patients Âgés ◽  
Treatment Regimens ◽  
Acute Myelogenous

Abstract Abstract 4353 Currrent therapy for acute myelogenous leukemia depends on the activity of cytosine arabinoside (ara-C). The development of regimens without this agent would potentially provide non-crossresistant treatment options for these disorders. Clofarabine, a novel agent showing significant single agent activity in AML, provides a platform for potentially effective treatment independent of ara-C. We treated 10 patients ages 30–67 (median 51) with relapsed or refractory AML with a phase I dose finding protocol employing a three drug combination based on clofarabine. The objectives were to define a maximally tolerated and recommended phase 2 dose and identify early phase 2 activity. Seven patients (70%) were refractory to 1 or 2 treatment regimens immediately prior to enrollment, the other 3 pts (30%) were relapsed following a remission. All patients had relapsed following or were refractory to standard 7+3 chemotherapy and 7/10 had received intermediate or high dose cytarabine within <52 weeks of enrollment. Patients received clofarabine 20mg/m2 (Dose level 1 – DL1 – 4 patients treated) or 25mg/m2 (DL2 – 6 patients) days 2–6, etoposide 100mg/m2 days 1–5, and mitoxantrone 8mg/m2 days 1–3. Treatment emergent non-hematological toxicities included mucositis (4 patients, ≤ grade 2) and diarrhea (2 patients, ≤ grade 3). Two out of 6 patients (33%) at DL2 failed to recover absolute neutrophils (ANC) to 500/mcL by Day 42, and this was judged a potentially treatment related toxicity given lack of residual leukemia in day 14 marrows. Seven of 9 (78%) day 14 marrows were markedly hypocellular or aplastic, and two showed residual leukemia. Four out of 10 patients (40%) showed complete remission (CR – 2 patients) or remission with incomplete hematopoietic recovery (CRi – 2 patients). Three patients survive in remission 34, 98, and 236 days from enrollment. We conclude that the clofarabine, etoposide and mitoxantrone combination has acceptable toxicity and is an active regimen for significantly pretreated acute myelogenous leukemia. The total response rate compares favorably with other AML salvage regimens. As there has been delayed myeloid recovery at higher doses, we are pursuing DL1. The activity of this regimen is potentially non-crossresistant with ara-C, therefore larger studies are justified. Currently, patients are enrolling in an expanded cohort at the recommend phase 2 dose. Disclosures: Claxton: Genzyme: Research Funding. Off Label Use: Clofarabine for AML therapy.

Consolidative Autologous Stem Cell Transplant for Double Hit Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3993-3993 ◽  
Author(s):  
Andy I Chen ◽  
Craig Okada ◽  
Nate Gay ◽  
Phil Reiss ◽  
Stephen Spurgeon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Conditioning Regimen ◽  
Treatment Algorithm ◽  
B Cell Lymphoma ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Double Hit Lymphoma ◽  
Double Hit

Abstract Double hit lymphoma (DHL), defined as B cell lymphoma with a c-MYC rearrangement plus a IGH/BCL2 rearrangement, confers a poor prognosis. Outcomes with R-CHOP are dismal with reported 2 year EFS <30% in multiple series. To improve upon these results, Burkitt type regimens such as R-HyperCVAD and dose adjusted (DA) R-EPOCH have been attempted, but 2 year EFS remains < 50% in early reports. In addition, the SWOG-9704 study found a benefit for consolidative autologous stem cell transplant (autoSCT) in high risk DLBCL, likely including some DHL, although this reported benefit has not been confirmed in three other randomized European studies. Since 2010 the treatment algorithm at Oregon Health & Science University for fit patients with DHL has been DA-R-EPOCH followed by consolidative autoSCT in responding patients. Here we report the first 16 patients treated with consolidative autoSCT. At diagnosis, the median age was 58, and the median IPI was 3. All patients had rearrangements of c-MYC and IGH/BCL2. One of the c-MYC rearrangements was a classical t(8;14); the translocation partners in the other cases were unknown. Three patients also had a ‘triple hit’ with an additional BCL6 rearrangement. Fourteen patients received DA-R-EPOCH with intrathecal prophylaxis for induction. One received R-CHOP at another institution, and one received R-HyperCVAD. 15 of 16 patients were in CR after induction. Stem cell mobilization was performed with G-CSF +/- plerixafor, and BEAM was utilized as the high dose conditioning regimen. With a median follow-up of 18 months, the estimated 2 year PFS is 91 %, and the 2 year OS is 91 % in the 16 patients who underwent consolidative autoSCT. There were no deaths from non-relapse mortality, and the only relapse was 6 months post-transplant. All other patients undergoing autoSCT remain alive and in remission. An additional 15 patients also underwent induction with DA-R-EPOCH but did not proceed to autoSCT. Four patients who had intended to undergo autoSCT were refractory to induction. Of the remaining 11 patients, 9 did not pursue autoSCT because of age and/or comorbidities, and 1 each declined out of personal preference or insurance denial. Four of these 11 have relapsed or died. Our results suggest that consolidative autoSCT, especially after DA-R-EPOCH induction, is an effective treatment strategy for DHL in fit patients and should be explored in prospective studies. Disclosures No relevant conflicts of interest to declare.

scholarly journals Traumatic submacular hemorrhage: available treatment options and synthesis of the literature

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Giamberto Casini ◽  
Pasquale Loiudice ◽  
Martina Menchini ◽  
Francesco Sartini ◽  
Stefano De Cillà ◽  
...  
Keyword(s):  
Intravitreal Injection ◽  
Case Reports ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Treatment Options ◽  
Young Patients ◽  
Treatment Strategies ◽  
Mechanical Damage ◽  
Invasive Treatment ◽  
Pneumatic Displacement

AbstractSub-macular hemorrhage (SMH) is a hematic collection between the neurosensory retina and the retinal pigment epithelium; one of its causes is ocular blunt trauma, that usually affects young patients. Persisting SMH leads to a damage of photoreceptors mediated by three main mechanisms: iron-related toxicity, impairment of diffusion of oxygen and nutriment, mechanical damage due to clot contraction. Since early photoreceptors’ damage has been reported within 24 h, it is suggested to provide an early treatment, although there are no guidelines or consensus between authors regarding treatment strategies. The aim of this review was to present and compare available treatment options, like intravitreal tissue plasminogen activator (tPA) associated with pneumatic displacement, pneumatic displacement alone, subretinal tPA injection with pneumatic displacement, and intravitreal anti-vascular endothelial growth factor (VEGF) injection. All procedures obtained consistent results, though the most effective seemed to be pars plana vitrectomy, subretinal tPA and gas tamponade, probably due to a quicker liquefaction and displacement of the clot. Limitations concern the greater invasiveness and the higher incidence of complications. Alternatively, intravitreal injection of tPA and gas may represent a less invasive option with fewer complications. Intravitreal injection of gas and prone position could be preferred in young patients without coexisting ocular pathology, being a minimally invasive treatment, with lower risk of complications and a good visual recovery. Anti-VEGF agent have found, to date, limited employment in cases of traumatic SMH even though they may be useful as alternative or adjuvant therapy. Most of the published literature consists of small studies and case reports, therefore further investigations and larger clinical trials are required to fully understand safety and efficacy of the procedures. A preoperative comprehensive evaluation may be helpful to realize a surgical plan tailored on patient.

scholarly journals Lack of Effectiveness of Intravenous High-Dose Methotrexate for Prevention of CNS Relapse in Patients with High-Risk DLBCL: A Retrospective Analysis from Alberta, Canada

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 26-27
Author(s):  
Robert Puckrin ◽  
Haidar El Darsa ◽  
Sunita Ghosh ◽  
Anthea Peters ◽  
Douglas A. Stewart
Keyword(s):  
High Risk ◽  
Lower Risk ◽  
High Dose ◽  
Cns Prophylaxis ◽  
Risk Criteria ◽  
Dose Methotrexate ◽  
Cns Relapse ◽  
Double Hit Lymphoma ◽  
Risk Patients ◽  
Double Hit

Introduction: Central nervous system (CNS) relapse occurs in 2-10% of patients with diffuse large B cell lymphoma (DLBCL) and carries a poor prognosis. The CNS-IPI score identifies patients at high-risk (10-12%) of CNS relapse based on the presence of 4-6 risk factors: age &gt;60 years, ECOG performance status &gt;1, elevated LDH, stage III to IV, &gt;1 extranodal site, and renal or adrenal involvement. International guidelines recommend prophylactic intravenous high-dose methotrexate (HD-MTX) for patients at high-risk of CNS relapse. However, there is limited evidence supporting this practice, and prophylactic HD-MTX requires hospital admission and increases the risk of treatment-related toxicity. Therefore, we conducted a real-world study to determine the effectiveness of HD-MTX for prevention of CNS relapse in high-risk DLBCL. Methods: We performed retrospective chart reviews of patients aged 18-70 years with DLBCL treated with curative intent at two academic medical centers in Alberta, Canada between 2012-2019. Since 2015, the Alberta Provincial Lymphoma Clinical Practice Guideline (APLCPG) has recommended CNS prophylaxis with HD-MTX 3.5g/m2 IV after cycles 2, 4, and 6 of R-CHOP for patients with the following high-risk criteria: CNS-IPI 4-6, double hit lymphoma, or testicular involvement. Between 2012-2015, HD-MTX was recommended for patients with elevated LDH, ECOG &gt;1, and &gt;1 extranodal site. In addition, eligible patients at risk of poor outcomes (e.g. double hit lymphoma or IPI score 4-5) could be offered higher intensity chemoimmunotherapy (e.g. da-EPOCH-R or R-CODOXM/R-IVAC) or R-CHOP followed by consolidative autotransplant. The log-rank test was applied to determine risk of CNS relapse and the Cox proportional-hazards model was used to determine factors associated with CNS relapse, progression-free survival (PFS), and overall survival (OS). Analyses were performed using SPSS version 25 and GraphPad Prism 8 statistical software. Results: We included 906 patients with a median follow-up time of 35.3 months (range 0.29-105.7). Risk of CNS relapse was 1.9% (95% C.I. 0.0-30.7%) for patients with CNS-IPI 0-1, 4.9% (95% C.I. 0.5-18.0%) for CNS-IPI 2-3, and 12.2% (95% C.I. 4.0-25.2%) for CNS-IPI 4-6 (p&lt;0.0001). Risk factors for CNS relapse included APLCPG high-risk criteria (HR 4.69, 95% C.I. 2.51-8.76), CNS-IPI score 4-6 (HR 4.26, 95% C.I. 2.22-8.16), and testicular involvement (HR 3.45, 95% C.I. 0.43-27.34). Among the 326 patients meeting APLCPG high-risk criteria, median CNS-IPI was 4 (range 0-6), 67 (20.6%) had double hit lymphoma, and 17 (5.2%) had testicular involvement. Risk of CNS relapse was significantly increased for patients meeting APLCPG high-risk criteria (11.8% vs 3.0%, p&lt;0.0001). Prophylactic HD-MTX was administered to 115 (35.3%) high-risk patients; median number of doses given was 2 (range 1-3). The risk of CNS relapse was 11.2% (95% C.I. 2.1-28.9%) for patients who received HD-MTX versus 12.2% (95% C.I. 2.8-28.8%) for those who did not (p=0.82). Patients who underwent higher intensity chemoimmunotherapy (n=35) or consolidative autotransplant (n=68) tended to have a lower risk of CNS relapse than patients treated with conventional R-CHOP (6.0% vs. 14.6%, p=0.09). In multivariate analyses, HD-MTX and higher intensity chemoimmunotherapy demonstrated no significant association with CNS relapse, PFS, or OS; however, consolidative autotransplant was associated with a tendency toward lower risk of CNS relapse (HR 0.30, 95% C.I. 0.09-1.01) and a significantly improved PFS (HR 0.41, 95% C.I. 0.24-0.71) and OS (HR 0.56, 95% C.I. 0.32-0.98). Conclusion: The APLCPG high-risk criteria of CNS-IPI 4-6, double hit lymphoma, or testicular involvement identify patients with DLBCL at significantly increased risk of CNS relapse. The risk of CNS relapse was similar for all high-risk patients (11.8%) and those who received prophylactic HD-MTX (11.2%) in our study relative to previously published data for patients who did not receive CNS prophylaxis (10-12%). Based on this analysis, we could not demonstrate a benefit to the current practice of prophylactic HD-MTX. However, the lower rate of CNS relapse and improved PFS and OS in patients who received consolidative autotransplant in our study suggests that optimizing frontline therapy to achieve better systemic disease control may be a more effective strategy to reduce the risk of CNS relapse than prophylactic HD-MTX alone. Disclosures Stewart: Teva: Honoraria; Sandoz: Honoraria; Novartis: Honoraria; AstraZeneca: Honoraria; Amgen: Honoraria; Roche: Honoraria; Janssen: Honoraria; Abbvie: Honoraria; Gilead: Honoraria; Celgene: Honoraria.

scholarly journals ML-03 RECONSIDERATION OF TREATMENT FOR ELDERLY PATIENTS WITH PRIMARY CENTRAL NERVE SYSTEM LYMPHOMAS

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii32-ii32
Author(s):  
Naoki Shinojima ◽  
Kenji Fujimoto ◽  
Keishi Makino ◽  
Takahiro Yamamoto ◽  
Jun-ichiro Kuroda ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Prognostic Factor ◽  
Tumor Cells ◽  
Protein Modification ◽  
Therapeutic Response ◽  
Young Patients ◽  
The Elderly ◽  
High Dose ◽  
High Group ◽  
Poor Prognostic Factor

Abstract BACKGROUND The therapeutic response to high-dose methotrexate therapy (HD-MTX) for primary central nervous system lymphoma (PCNSL) varies. Polyglutamylation (PG) is a reversible protein modification, tumor cells show frequent occurrence of PG. Intracellularly polyglutamylated MTX is not subject to competitive inhibition by leucovorin (LV). Tumor cells with high PG levels are selectively killed, whereas normal cells with lower PG are rescued by LV. We previously reported that PG is a predictor of therapeutic response to HD-MTX in PCNSL. However, PG did not affect overall survival (OS) in the elderly unlike the young patients, suggesting that there are other significant predictors in the elderly. The aim of this study is to identify the prognostic factors in aged PCNSL. METHODS The prognostic factors were investigated in 48 patients (M/F=23/25) aged 65 and older undergoing HD-MTX in our institute with data of area under the concentration-time curve of MTX, AUCMTX (μmol/L/h). RESULTS The median OS of elderly PCNSL was 937days. In the AUCMTX high group (median 1706.3 or more, n=24) and the low group (median below, n=24), OS was significantly shortened in the high group compared with the low group (median 728 vs 1290days, p=0.032). Even in multivariate analysis, AUC was the only independent poor prognostic factor of OS (p=0.031). On the other hand, AUC was not a prognostic factor for OS in PCNSL younger than 65 years. AUCMTX of aged PCNSL was significantly higher compared with younger patients (p&lt;0.01). These results suggested that PG may be a good prognostic factor of OS when AUCMTX is low. CONCLUSION In the aged PCNSL, OS was shortened when AUCMTX was high. With the results of the previous research, it is suggested that if PG levels is high in elderly PCNSL, the OS prolongation can be expected if the MTX dose is reduced.

scholarly journals Hodgkin Lymphoma—Review on Pathogenesis, Diagnosis, Current and Future Treatment Approaches for Adult Patients

2021 ◽  
Vol 10 (5) ◽  
pp. 1125
Author(s):  
Jesko Momotow ◽  
Sven Borchmann ◽  
Dennis A. Eichenauer ◽  
Andreas Engert ◽  
Stephanie Sasse
Keyword(s):  
Hodgkin Lymphoma ◽  
Treatment Options ◽  
Young Patients ◽  
High Dose Chemotherapy ◽  
Salvage Chemotherapy ◽  
Current Treatment ◽  
High Dose ◽  
Line Treatment ◽  
Comprehensive Overview ◽  
Rare Malignancy

Hodgkin lymphoma (HL) is a rare malignancy accounting for roughly 15% of all lymphomas and mostly affecting young patients. A second peak is seen in patients above 60 years of age. The history of HL treatment represents a remarkable success story in which HL has turned from an incurable disease to a neoplasm with an excellent prognosis. First-line treatment with stage-adapted treatment consisting of chemotherapy and/or radiotherapy results in cure rates of approximately 80%. Second-line treatment mostly consists of intensive salvage chemotherapy followed by high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). Novel approaches such as antibody drug conjugates and immunomodulatory drugs have shown impressive results in clinical trials in refractory and relapsed HL and are now increasingly implemented in earlier treatment lines. This review gives a comprehensive overview on HL addressing epidemiology, pathophysiology and current treatment options as well as recent developments and perspectives.

scholarly journals Strategizing the Treatment Approach to Acute Myeloid Leukemia

2021 ◽  
pp. 1-6
Author(s):  
Laura Finn ◽  
Michael Lunski ◽  
Saikrishna Gadde ◽  
Matthew Alberti ◽  
Danny Markabawi ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Molecular Classification ◽  
Ongoing Research ◽  
Molecular Alterations ◽  
Treatment Regimens ◽  
New Treatments ◽  
Acute Myeloid

For decades acute myeloid leukemia, the primary acute leukemia affecting adults, had limited treatment options. Since 2017, we have seen discovery and development in cytogenetic and molecular classification of acute myeloid leukemia, improved understanding of cell signaling pathways, and development of new treatment for acute myeloid leukemia. These new treatments include novel combinations of agents and therapy targeting molecular alterations improving rates of remission and overall survival. Treatment discovery provides therapeutic opportunity to older patients and populations previously excluded from intense induction chemotherapy. In this review, we discuss the timing of first therapy, non-intense treatment regimens achieving remission, and new targets for directed therapy. We reference key clinical trials to expand our discussion of newly approved agents for acute myeloid leukemia. In this review, we highlight the discovery of treatment strategies to improve patient outcomes and ongoing research in leukemia.

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