Effectiveness of mycophenolate mofetil as first-line therapy in AQP4-IgG, MOG-IgG, and seronegative neuromyelitis optica spectrum disorders

2016 ◽  
Vol 23 (10) ◽  
pp. 1377-1384 ◽  
Author(s):  
Alexis Montcuquet ◽  
Nicolas Collongues ◽  
Caroline Papeix ◽  
Helene Zephir ◽  
Bertrand Audoin ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Neuromyelitis Optica ◽  
Post Treatment ◽  
First Line ◽  
Treatment Change ◽  
Good Tolerability ◽  
First Line Therapy ◽  
Line Therapy ◽  
Pre Treatment

Objective: To evaluate the effectiveness and tolerance of mycophenolate mofetil (MMF) as a first-line treatment in neuromyelitis optica spectrum disorder (NMOSD). Methods: In all, 67 NMOSD patients treated by MMF as first-line therapy, from the NOMADMUS cohort were included. A total of 65 fulfilled 2015 NMOSD criteria, and 5 were myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG) positive. Effectiveness was evaluated on percentage of patients continuing MMF, percentage of patients free of relapse, pre- and post-treatment change in the annualized relapse rate (ARR), and Expanded Disability Status Scale (EDSS). Results: Among 67 patients, 40 (59.7%) continued treatment till last follow-up. A total of 33 (49.3%) were relapse-free. The median ARR decreased from one pre-treatment to zero post-treatment. Of 53 patients with complete EDSS data, the score improved or stabilized in 44 (83%; p < 0.05). Effectiveness was observed in aquaporin-4 (AQP4)-IgG (57.8% continued treatment, 46.7% relapse-free), MOG-IgG (3/5 continued treatment, 4/5 relapse-free), and seronegative NMOSD (64.7% continued treatment, 61.3% relapse-free). In 16 patients with associated steroids, 13 (81.2%) continued MMF till last follow-up versus 15 of 28 (53.6%) in the non-steroid group. Nine patients discontinued treatment for tolerability purpose. Conclusion: MMF showed effectiveness and good tolerability as a first-line therapy in NMOSD, whatever the AQP4-IgG status. Concomitant use of oral steroids at start could limit the risk of treatment failure.

Utility Of Post Therapy Brain Surveillance Imaging In The Detection Of Primary CNS Lymphoma (PCNSL) Relapse

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 933-933
Author(s):  
Gaelle Fossard ◽  
Emmanuelle Nicolas-Virelizier ◽  
Philippe Rey ◽  
Francois Ducray ◽  
Emmanuel Jouanneau ◽  
...  
Keyword(s):  
Brain Imaging ◽  
Primary Cns Lymphoma ◽  
Post Treatment ◽  
Cns Lymphoma ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Surveillance Imaging ◽  
Treatment Observation

Abstract Introduction The optimal follow-up strategy for primary CNS lymphoma (PCNSL) patients in remission after first line therapy is not clear. The goal of this study is to determine the utility of planned brain surveillance imaging in the detection of relapse in a large cohort of PCNSL patients. Methods Patients were from consecutive PCNSL cases (N=209) included in Leon Berard Cancer Centre registry (Lyon, France), from 1987 to 2011 (date of diagnosis). Patients were all treated by chemotherapy, 92% of them by high-dose methotrexate containing chemotherapy followed by brain radiotherapy for 107 patients (51%). All patients were followed for relapse, retreatment and death. Patient clinical records were reviewed for details at relapse and relationship to planned follow-up visits and brain surveillance imaging. Results Among the 209 PCNSL patients, 28 (13%) presented toxic death, one patient died from another reason and 41 patients (20%) had a progressive disease during first-line therapy. The remaining 139 patients (66%) entered in post-treatment observation, 128 of them in complete remission (92%) and 11 in partial remission (8%). The median follow up was 36 months for the patients who entered in post-treatment observation. Among these 139 patients, 7 (5%) were lost of follow-up, 62 (45%) patients are still in remission and 70 (50%) relapsed. Among these 70 relapses, 15 (21%) were detected by planned brain surveillance imaging but 53 (76%) patients were symptomatic and presented earlier than a planned follow-up visit; two patients (3%) had no information at time of relapse. If we consider only patients in complete remission who entered in post-treatment observation, 13 (20%) relapses were detected by brain surveillance imaging and 50 (80%) patients presented symptoms between planned visits and imaging. Among the 7/11 patients considered in partial remission after initial treatment who relapsed, two (29%) relapses were detected by brain surveillance imaging and five (71%) by symptoms between planned visits and imaging. Among the 53 symptomatic patients at relapse, 41 (77%) presented a brain tumor relapse, six had an isolated leptomeningeal relapse, one a spinal cord localization and five an extra-cerebral relapse (three abdominal nodes, one soft-tissue mass, one testis). The most common symptoms at relapse were cognitive troubles, motor or sensitive deficits, epilepsy, and alteration of performance status. We did not observe any difference between asymptomatic relapse patterns before and after 2 years with 54% relapses before the two years of follow-up (brain imaging mainly every 4 months) and 46% relapses after 2 years of follow-up (brain imaging mainly every 6 months). Conclusions This study showed that PCNSL relapses frequently occurred outside of planned follow-up visits and were notably detected by symptoms between two brain surveillance imaging. Even during the two first years of follow-up with a closed brain imaging monitoring, planned surveillance imaging seemed not efficient. Disclosures: No relevant conflicts of interest to declare.

Favorable Molecular Responses to Imatinib in CML Patients in Early Chronic Phase in Comparison to Late Chronic Phase Patients after Treatment with Hydroxyurea and Interferon.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4794-4794
Author(s):  
Frank Schüler ◽  
Malte Leithäuser ◽  
Thomas Kiefer ◽  
Saskia Richter ◽  
Gottfried Dolken
Keyword(s):  
Chronic Phase ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Transcript Levels ◽  
Log Reduction ◽  
First Line Therapy ◽  
Line Therapy ◽  
Pre Treatment

Abstract Peripheral blood samples from 70 patients treated with imatinib were regularly sent to us for the determination of bcr-abl transcript levels by a standardized quantitative real-time PCR (TaqMan®). 45 patients with early chronic phase CML were treated with imatinib as a first line therapy and 25 patients in late chronic phase received imatinib as a second line therapy after hydroxyurea plus interferon. The median pre-treatment time with hydroxyurea plus interferon in these late chronic patients was 43 months (6 – 130). The median follow-up was 18.4 months (1–51) for first line patients and 18.0 months (1–48) for second line patients. Patients received a median dosage between 400–600 mg imatinib in both groups. At the time of diagnosis the median bcr-abl/abl ratio was 248 % (26–460%, SD: 148%) in patient receiving imatinib as a first line treatment. Patients receiving imatinib as second line treatment had a median bcr-abl/abl ratio of 24,84% (1–256%, SD: 78%) just before the imatinib treatment was initiated. Early chronic phase CML patients treated with imatinib as a first line therapy showed a strong biphasic decay of their bcr-abl transcript with a fast reduction between 1-2-log during the first 6–9 months followed by a slower rate of reduction afterwards. A bcr-abl/abl ratio &lt;0.1% could be observed in 19/51 (37%) patients and in 12/51 (23%) patients a bcr-abl/abl ratio &lt; 0.01% was found. After 18 months of therapy the median reduction of bcr-abl was about 2.5-log, after 36 months about 3-log. 12/51 (23%) patients showed a suboptimal response or had a subsequent increase of their bcr-abl transcript levels. Best responding patients could be identified by a &gt;2-log reduction after 6 months and &gt; 3-log reduction after 18 months of therapy. In late chronic phase CML patients pre-treated with hydroxyurea and interferon the overall median decrease of bcr-abl transcript levels was about 1-log after a median follow-up of 18 as well as after 36–48 months. Obviously, there are at least three subgroups of patients with a different molecular response. We identified 7/25 (28%) patients with no significant reduction of bcr-abl transcripts after 18 months as well as after 36 months of imatinib therapy. In contrast, another group of 4/25 (16%) patients showed a 2-log reduction of bcr-abl/abl ratio after 18 months with a subsequent reduction of 3-log after 36 months. Within the largest group of 14/25 (56%) patients a 1-log reduction after 18 months and a 1-2-log reduction after 36 months was observed. No patient had &gt; 3-log reduction within the whole group of 25 late chronic phase patients. The reduction of bcr-abl transcript levels as a result of imatinib therapy is significantly superior in CML patients receiving imatinib as first line treatment for CML in early chronic phase compared to patients treated with imatinib after a long term pre-treatment with hydroxyurea and interferon.

scholarly journals GCT-28. RECURRENCE PATTERN AND SURVIVAL FOR RELAPSED INTRACRANIAL NON-GERMINOMATOUS GERM CELL TUMORS: A SINGLE-INSTITUTION EXPERIENCE

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii333-iii333
Author(s):  
Lei Wen ◽  
Zhaoming Zhou ◽  
Qingjun Hu ◽  
Juan Li ◽  
Mingyao Lai ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
Late Recurrence ◽  
Salvage Chemotherapy ◽  
Recurrence Time ◽  
First Line ◽  
Primary Tumor Site ◽  
First Line Therapy ◽  
Line Therapy

Abstract PURPOSE Intracranial non-germinomatous germ cell tumors (NGGCTs) have lower overall survival than germinoma because relatively higher recurrence usually occurs after first line therapy. METHODS Between January 2003 and December 2018, 111 consecutive patients diagnosed with NGGCTs reviewed. Those who progressed after first line therapy were included in this study. Data of first line treatment, salvage treatment, clinicopathological features and survival were collected and analyzed. RESULTS Totally, thirty patients (30/111, 27.0%) relapsed in our cohort, including 19 patients with accurate relapse information detail, and 11 patients who died of disease progression during follow up but without exact time and site of relapse. The median OS from diagnosis of the disease was 49.2 months (95% CI: 14.1 to 84.3 months) and 3-year OS was 54.3%. Patients who received both CSI and chemotherapy relapsed less than those who received reduced volume of radiotherapy or only CSI or only chemotherapy (22.5% vs. 45.5%, p=0.034). Of 19 patients who had detail information of recurrence time and site, the median time from diagnosis of disease to relapse was 9.5 months (2.2 to 72.1 months). Regarding to recurrence site, most patients relapsed in primary site (10/19, 52.6%) or distant intracranial (6/19, 31.6%). The recurrence site of other 3 patients were spinal (n=1), ventricular (n=1) and peritoneal (n=1). CONCLUSION Protracted follow-up is recommended because late recurrence is not uncommon. Primary tumor site and distant intracranial are the most prevalent relapsed location. Patients who relapsed could benefited from both CSI and salvage chemotherapy.

scholarly journals A Female with Evans Syndrome Presented with Pancytopenia

2021 ◽  
Vol 10 (2) ◽  
pp. 114-117
Author(s):  
Md Rezaul Karim Chowdhury ◽  
Md Haroon Ur Rashid ◽  
Md Mahbub Hossain ◽  
Shafayet Hossain Riyan
Keyword(s):  
Oral Prednisolone ◽  
Low Grade ◽  
Evans Syndrome ◽  
First Line ◽  
Indirect Bilirubin ◽  
First Line Therapy ◽  
Line Therapy ◽  
Immune Neutropenia ◽  
Chronic Course

Evans syndrome is an uncommon haematological disorder characterised by autoimmune haemolytic anaemia (AIHA), immune thrombocytopenia (ITP) and/or immune neutropenia. It may occur in all ethnic groups, all ages and has no sex predilection. The direct antiglobulin test (DAT) is almost invariably positive. This condition generally runs a chronic course and is characterised by frequent exacerbations and remissions. Corticosteroids and/or intravenous immunoglobulin (IVIG) are the most commonly used first line therapy. Here we report a case of a female who presented with severe shortness of breath, palpitation and low grade fever and on examination she was found severely pale and mildly icteric. Her CBC and PBF showed pancytopenia. Indirect bilirubin and LDH were raised and direct Coomb’s test was positive. She was labeled as a case of Evans syndrome and responded to oral prednisolone. On subsequent follow-up her haematological profiles remained normal. J Enam Med Col 2020; 10(2): 114-117

High-Dose Bi-Weekly THP-COP Induction Treatment Followed by High-Dose Therapy with Autologous Peripheral Blood Stem Cell Transplantation for Advanced-Stage Follicular Lymphoma as First-Line Therapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5207-5207
Author(s):  
Sadao Aoki ◽  
Jun Takizawa ◽  
Masutaka Higashimura ◽  
Akihito Momoi ◽  
Nobuhiro Tsukada ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Cell Transplantation ◽  
High Dose ◽  
Advanced Stage ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Abstract Introduction: Most patients with advanced-stage follicular lymphoma(FL) cannot be cured by conventional chemotherapy and have median survival of 7 to 10 years. High-dose chemotherapy (HDT) supported by autologous stem cell transplantation(ASCT) gives a survival benefit for patients with aggressive lymphoma. Recent several multicenter studies have shown that clinical and molecular remissions can be attained in patients with FL receiving intensified high-dose sequential chemotherapy and autografting. We have reported the efficacy and safety of high-dose bi-weekly THP-COP with G-CSF support (HDBW-TCOPG) for non-Hodgkin’s lymphoma. Therefore, we performed a pilot clinical trial to evaluate the efficacy and toxicity of HDBW-TCOPG followed by HDT with ASCT as first-line therapy in patients with advanced-stage FL. Patients and methods: Between August 1998 and December 2003, 10 Japanese patients with previously untreated FL from whom informed consent was obtained were included in this single-center pilot study. Median age was 48 years. All patients had stage 3 or 4 disease, aaIPI LI 8 and HI 2. Histological subtypes of FL included grade 1 4; grade 2 4; grade 3a 2. HDBW-TCOPG consisted of pirarubicin 70 mg/m2 on day 1; cyclophosphamide 1000 mg/m2 on day 1; vincristine 1.4 mg/m2 on day 1; predonisolone 50 mg/m2 from day 1 to 5; lenograstim 2.0 mg/kg/day from day 3. Five patients who enrolled after rituximab was approved for indolent B-cell lymphoma in Japan received induction therapy combined HDBW-TCOPG with rituximab 375mg/m2 on day -2 (R-HDBW-TCOPG). Six cycles were administered at intervals of two weeks. PBSC were collected during the later cycles of HDBW-TCOPG or on the recovery of high-dose etoposide regimen (500mg/m2 for 3 days) administered after the completion of HDBW-TCOPG. Leukaphereses were performed until a minimum of 2.0x106/kg CD34+ cells had been collected. The conditioning regimen consisted of ranimustine 200mg/m2 on day-7 and -2; paraplatin 300mg/m2 on day -6, -5, -4, -3; etoposide 500mg/m2 on day −5, −4, −3; cytarabine 2.5 g/m2 every 12 hours on day −2, −1 (MCE-CA regimen) in 2 patients or cyclophosphamide 50mg/kg on day −2, −1 (MCEC regimen) in 8 patients. Results: Sufficient numbers of PBSC were collected in 5 of 7 patients mobilized with HDBW-TCOPG and in all 5 patients with high-dose etoposide. The median time to reach total number of leukocytes of 1.0 x109/l was nine days (range 8–11). All 10 patients who were in PR at the end of HDBW-TCOP(G) achieved CR post APBSCT. After a median follow up of 36.6 months (range 7–66 months) PFS and OS are 90% and 90%, respectively, for all patients. One patient developed secondary myeloid leukemia with t(3;21) and died at 35 months after APBSCT without signs of recurrence of lymphoma. Another patient who relapsed at 35 months after transplantation. IgH or BCL2 rearrangement was detected by PCR analysis prior to therapy in three patients and one of them still showed detectable disease after HDBW-TCOPG induction. However, all three patients demonstrated MRD negativity after HDT with ASCT. Conclusion: HDBW-TCOPG as induction therapy followed by HDT with ASCT is feasible for advanced-stage FL with acceptable toxicity, and this short term highly intensified therapy may induce cure of the disease by minimizing MRD, but longer follow up is needed to evaluate the impact on survival.

Reduced Intensity Stem Cell Transplantation and Donor Lymphocyte Infusion after Imatinib Induction To Eradicate Residual Disease in Chronic Myeloid Leukaemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1097-1097
Author(s):  
Nicholas Heaney ◽  
Mhairi Copland ◽  
Karen Stewart ◽  
Judith Godden ◽  
Anne Parker ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Disease Control ◽  
Cell Transplantation ◽  
Residual Disease ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Reduced Intensity

Abstract Recommended first-line therapy for patients with chronic phase (CP) CML is imatinib mesylate (IM). Although IM induces complete cytogenetic responses (CCR) in the majority of patients, disease often remains detectable by Q-RT-PCR, likely reflecting stem cell persistence. Furthermore, primary and acquired resistance to IM have led to concerns about response durability. Allogeneic stem cell transplantation (SCT) remains the only curative option and with reduced intensity conditioning (RISCT) is less toxic and may be offered to a broader patient group. Our novel approach used IM to establish disease control (CCR) in patients with newly diagnosed CP CML prior to RISCT (fludarabine/melphalan/MabCampath). Prophylactic escalating DLI was given for residual disease. 18 patients (4 centres) were recruited between 2001 and 2006. Of these, 3 received myeloablative SCT, 2 for progression to blast crisis prior to SCT and the third for failing to reach a major cytogenetic response. 15 patients with a median age of 39y (21–56y) received sibling RISCT. Hasford scores were 38% low, 54% intermediate and 8% high risk. EBMT risk scores were 1–2 (13 patients) and 3–4 (2 patients). 5 patients required IM dose escalation to achieve CCR prior to RISCT. Follow-up data extends to a median of 31 (12–61) months (m) post RISCT. The RISCT procedure was well tolerated with rapid engraftment and short in-patient stays. 53% had infective episodes post RISCT, including CMV reactivation (86% patients at risk), EBV+ post transplant lymphoproliferative disease (2 patients) and PCP (1 patient). 1 patient developed aGvHD (grade III) and 8 cGvHD (6 limited, 2 extensive). DLI was given to 13 patients (87%), 6 for elevated Bcr-Abl, 4 for mixed chimerism and 2 for both. The median total dose was 0.65 × 107CD3+cells/kg (0.1–6.65 × 107cells/kg) in a median of 2 infusions. GvHD was seen in 6 of 12 patients receiving DLI (50%). IM was required in 4 patients with residual disease and all discontinued IM once disease control was re-established (4–13m of IM). 1 of 15 transplanted has died (at 12m with GvHD and infection). Of surviving patients median Bcr-Abl measurements fell as follow-up progressed. 8 patients currently have sustained undetectable Bcr-Abl. 7 of these 8 received DLI, the other had GvHD. The interval between last DLI and first proof of disease eradication was median 2m (range 1–28m). Only 2 of these 8 patients received IM post-transplant. In this study, the patients receiving RISCT were in early CP with a CCR to IM. It is likely that the majority would have maintained CCR if not offered transplantation. However the number of patients who achieved undetectable Bcr-Abl following RISCT and DLI compares favourably with the response expected with IM alone. The patients have tolerated the transplant procedure well and are currently off all treatment for CML. Regular monitoring remains necessary, however if relapse occurs it should be DLI responsive. Currently IM is the accepted first line therapy in the majority of patients however we would highlight the importance of RISCT in selected groups and believe our approach is effective and well tolerated.

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