scholarly journals First-line high-dose therapy and autologous blood stem cell transplantation in patients with primary central nervous system non-Hodgkin lymphomas—a single-centre experience in 61 patients

2022 ◽  
Author(s):  
T. Brezina ◽  
H. von Dewitz ◽  
T. Schroeder ◽  
S. Ullrich ◽  
K. Nachtkamp ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Autologous Blood ◽  
High Dose ◽  
First Line ◽  
High Dose Therapy ◽  
Blood Stem Cell Transplantation

AbstractPrimary central nervous system non-Hodgkin lymphomas (PCNS-NHLs) are extranodal B-cell lymphomas with poor prognosis. The role of high-dose therapy (HDT) followed by autologous blood stem cell transplantation (ASCT) as first-line therapy is still not clear. We retrospectively collected long-term follow up data of 61 consecutive patients with PCNS-NHL at the University Hospital Düsseldorf from January 2004 to December 2016. Thirty-six patients were treated with conventional chemoimmunotherapy (cCIT) only (CT-group). Seventeen patients received an induction cCIT followed by HDT and ASCT. In the CT-group, the overall response rate (ORR) was 61% (CR 47%, PR 14%), and there were 8% treatment-related deaths (TRD). Progression-free survival (PFS) was 31.8 months, and overall survival (OS) was 57.3 months. In the HDT-group, the ORR was 88% (59% CR, 29% PR), and there were 6% TRD. Median PFS and OS were not reached at 5 years. The 5-year PFS and OS were 64.7%. After a median follow up of 71 months, 10 patients (59%) were still alive in CR/PR following HDT and ASCT, one patient was treated for progressive disease (PD), and 7 had died (41%, 6 PD, 1 TRD). All patients achieving CR prior to HDT achieved durable CR. In the CT-group, 8 patients (22%) were alive in CR/PR after a median follow-up of 100 months. Twenty-eight patients died (78%, 24 PD, 2 TRD, 2 deaths in remission). In the univariate analysis, the HDT-group patients had significantly better PFS (not reached vs 31.8 months, p = 0.004) and OS (not reached vs 57.3 months, p = 0.021). The multivariate analysis showed HDT was not predictive for survival. Treatment with HDT + ASCT is feasible and offers the chance for long-term survival with low treatment-related mortality in younger patients. In this analysis, ORR, PFS and OS were better with HDT than with conventional cCIT alone. This result was not confirmed in the multivariate analysis, and further studies need to be done to examine the role of HDT in PCNSL.

Cytarabine and Etoposide (CYVE) as First-Line Therapy for Primary Central Nervous System Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4895-4895
Author(s):  
Jonathan How ◽  
Margaret Warner ◽  
Chaim Shustik ◽  
Pierre Laneuville
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Febrile Neutropenia ◽  
Salvage Therapy ◽  
Central Nervous System Lymphoma ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Abstract Abstract 4895 Background: The treatment of primary central nervous system lymphoma (PCNSL) is characterized by high rates of toxicity and intracranial relapse despite initial response. High-dose methotrexate (HD-MTX), with or without cranial irradiation, has become the standard of care; combining this with other chemotherapeutic agents has improved complete remission rates but at the expense of increased treatment-related adverse events, particularly haematologic and neurologic toxicity. Cytarabine has been used in combination with etoposide (CYVE) as a salvage therapy for patients who have been refractory to or relapsed after HD-MTX-based regimens (Soussain C et al, J. Clin. Oncol. 2001; Soussain C et al, J. Clin. Oncol. 2008). In these studies, cytarabine was given as an infusion at a dose of 50mg/m2/d over 12 hours on days 1–5, and at a dose of 2g/m2/d over 3 hours on days 2–5 with etoposide at 200mg/m2/d on days 2–5. Both responders and non-responders were eligible to proceed to autologous stem cell transplant (autoSCT) using a conditioning regimen of thiotepa 250mg/m2/d on days -9 to -7, busulfan 10mg/kg total dose po or 8mg/kg total dose iv over days -6 to -4, and cyclophosphamide 60 mg/m2/d on days -3 to -2. Median OS was 58.6 months in patients able to undergo autoSCT, but with significant neurotoxicity that may have been related in part to prior therapies. Methods and Results: Given its excellent CNS penetration, CYVE may be an effective regimen in previously untreated patients, with lower risk of neurotoxicity. We have used CYVE as a first-line therapy for patients with PCNSL who are potentially eligible for subsequent autoSCT. Between January 1, 2005 and December 31, 2009, 7 patients with a diagnosis of PCNSL were treated with first-line CYVE using the regimen described above. All were HIV negative, showed no disease outside of the CNS on bone marrow biopsy and staging CT or PET scan, and had biopsy-proven PCNSL with diffuse large B-cell histology. Median age was 55 (42-61) with 4 female and 3 male patients. Median International Extranodal Lymphoma Study Group Prognostic Index score was 2 (0-2), although in actuality may have been higher, as 4 patients were not able to undergo lumbar puncture at diagnosis. ECOG status was < 2 in 3 patients, ≥ 2 in 3 patients, and not documented in 1 case. Patients received a median of 2 cycles of CYVE (1-3), with 2 receiving concurrent rituximab and the 1 patient with intra-ocular lymphoma receiving post-adjuvant orbital radiation. No cranial radiation was administered. Five patients achieved CR and proceeded to autoSCT. Two patients had a PR but later died of progressive disease at day +48 and day +117, respectively. In both cases, however, the patients were suspected of having disease long before they were treated with CYVE. The first had presented 3 years prior to the diagnosis with a solitary brain lesion that resolved with decadron monotherapy before pathologic documentation. The second had had a brain biopsy that failed to show malignant disease 4 months before the PCNSL diagnosis was confirmed and treatment initiated. Median OS and PFS for the group have not yet been reached with mean follow-up of 657 days. Among the 5 patients who achieved CR, all patients remain alive in CR with a mean follow-up of 841 days (320-1262 days), or 28 months. Toxicities included at least 1 episode of febrile neutropenia in all 7 patients, 2 possible but unconfirmed cases of pulmonary aspergillosis, 2 cases of drug-induced hepatitis (with ALT > 3x ULN), 1 case of toxic epidermal necrolysis secondary to imipenem use during an episode of febrile neutropenia, 1 small bowel obstruction requiring surgical intervention, and 1 case of late grade 2 neurotoxicity presenting 3 years after treatment. Conclusions: In this small cohort of patients, first-line CYVE has shown to be highly effective (ORR 100%, CR 71%) with minimal long-term toxicity compared to that which is seen using it as a salvage therapy. When followed by autoSCT, long-term survival with preserved quality of life may be possible. A prospective study would be necessary to confirm these initial results in practice. Disclosures: No relevant conflicts of interest to declare.

High-Dose Therapy and Autologous Blood Stem-Cell Transplantation Compared With Conventional Treatment in Myeloma Patients Aged 55 to 65 Years: Long-Term Results of a Randomized Control Trial From the Group Myelome-Autogreffe

2005 ◽  
Vol 23 (36) ◽  
pp. 9227-9233 ◽  
Author(s):  
Jean-Paul Fermand ◽  
Sandrine Katsahian ◽  
Marine Divine ◽  
Veronique Leblond ◽  
Francois Dreyfus ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Blood ◽  
High Dose ◽  
Newly Diagnosed ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Blood Stem Cell Transplantation

Purpose To study the impact of high-dose therapy (HDT) with autologous stem-cell support in patients with symptomatic multiple myeloma (MM) between the ages of 55 and 65 years. Patients and Methods One hundred ninety patients between 55 and 65 years old who had newly diagnosed stage II or III MM were randomly assigned to receive either conventional chemotherapy (CCT; ie, monthly courses of a regimen of vincristine, melphalan, cyclophosphamide, and prednisone) or HDT and autologous blood stem-cell transplantation (using either melphalan alone 200 mg/m2 intravenous [IV] or melphalan 140 mg/m2 IV plus busulfan 16 mg/kg orally as pretransplantation cytoreduction). Results Within a median follow-up of 120 months, median event-free survival (EFS) times were 25 and 19 months in the HDT and CCT groups, respectively. Median overall survival (OS) time was 47.8 months in the HDT group compared with 47.6 months in the CCT group. A trend to better EFS (P = .07) was observed in favor of HDT, whereas OS curves were not statistically different (P = .91). The period of time without symptoms, treatment, and treatment toxicity (TwiSTT) was significantly longer for the HDT patients than for the CCT patients (P = .03). Conclusion With a median follow-up time of approximately 10 years, this randomized trial confirmed a benefit of HDT in terms of EFS and TwiSTT but did not provide evidence for superiority of HDT over CCT in OS of patients aged 55 to 65 years with symptomatic newly diagnosed MM.

scholarly journals Diagnosis, treatment, and misdiagnosis analysis of 28 cases of central nervous system echinococcosis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Guojia Du ◽  
Yandong Li ◽  
Pan Wu ◽  
Xin Wang ◽  
Riqing Su ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Clinical Features ◽  
Multiple Organ ◽  
Pathological Examination ◽  
Surgical Removal ◽  
Surgical Treatments

Abstract Background To explore central nervous system (CNS) involvement in this disease, from the perspectives of diagnosis, treatment, and misdiagnosis Methods Twenty-eight patients with CNS echinococcosis were included in this retrospective study, including 18 males (64.3%) and 10 (35.7%) females. The average age of all the patients were 23.5 years (ranged 4–60 years). Twenty-three (23) patients (82.1%) received the first surgical resection in our hospital. Five (5) patients (17.9%) gave up surgical treatment for multiple-organ hydatidosis and previous surgery history at other hospitals, and albendazole was applied for a long-term (3–6 months) adjunct therapy for the 5 patients. The average follow-up time was 8 years. Results For the 28 patients, 23 cases received surgical treatments, and the diagnosis was confirmed by pathological examinations. The diagnosis of 4 cases of brain echinococcosis and 2 cases of spinal cord echinococcosis could not be confirmed, resulting in a misdiagnosis rate of 21.4% (6/28). For the pathological examination, a total of 17 cases were infected with Echinococcus granulosus (including 2 cases of spinal cord echinococcosis), and 6 cases were infected with Echinococcus alveolaris. Conclusion The diagnosis should be specifically considered in endemic regions. The clinical features of CNS hydatidosis were intracranial space-occupying lesions. For the treatment, the surgical removal of cysts should be necessary. In addition, the adjuvant therapy with drug and intraoperative prophylaxis is also suggested. The misdiagnosis may have resulted from atypical clinical features and radiographic manifestations, as well as the accuracy of hydatid immunologic test.

CNS Stimulant Controversies

1989 ◽  
Vol 23 (4) ◽  
pp. 497-502 ◽  
Author(s):  
Florence Levy
Keyword(s):  
Central Nervous System ◽  
Animal Model ◽  
Nervous System ◽  
High Dose ◽  
Ethical Considerations ◽  
Hyperactivity Disorder ◽  
Central Nervous System Stimulant ◽  
Stimulant Medications ◽  
Cns Stimulant

Controversies in the use of central nervous system stimulant medications in children with attention deficit hyperactivity disorder are discussed. Diagnostic issues, age of optimal use, side effects, effects on learning and ethical considerations are current issues. An animal model for the effects of chronic long-term high dose regimes is proposed.

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