Chlorambucil PLUS Rituximab As FRONT-LINE THERAPY in Elderly or Unfit Patients Affected by B-CELL Chronic Lymphocytic Leukemia: Results of A Single-Centre Retrospective Analysis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4604-4604
Author(s):  
Luca Laurenti ◽  
Barbara Vannata ◽  
Idanna Innocenti ◽  
Francesco Autore ◽  
Francesco Santini ◽  
...  
Keyword(s):  
Median Time ◽  
Conflicts Of Interest ◽  
Complete Response ◽  
Fish Analysis ◽  
Median Dose ◽  
Bulky Disease ◽  
Overall Response ◽  
Line Therapy ◽  
Trisomy 12 ◽  
Unfit Patients

Abstract Abstract 4604 Currently standard first line therapy for fit patients with B-CLL/SLL are fludarabine-based regimens. Elderly patients or patients with comorbidities poorly tolerate purine analogue-based chemotherapy and they are often treated with Chlorambucil (Chl). However, complete response (CR) and overall response (OR) rates with Chl are relatively low. We now investigated whether the addition of Rituximab to Chl will improve the efficacy without impairing the tolerability in elderly and unfit patients. We included in our study 23 elderly or unfit patients that had not received prior therapy. All patients were treated with Chl (1mg/Kg monthly for 8 cycles) plus Rituximab (375 mg/m2 for the first course and 500 mg/m2 for subsequent cycles until the 6th cycle). Fifteen patients were male and 8 were female, with a median age at the time of treatment of 70 years (range 58 to 81 years). Eight patients (35%) were unfit with a median age of 68 years (range 58 to 79 years). Five patients were in stage A/I, 10 were in stage B/II and 8 in stage C/IV. FISH analysis was done in all patients: 78% showed karyotype abnormalities. Low-risk FISH karyotype was detected in 20/23 pts: 12 of them had del(13q14), 1 had trisomy 12, 1 trisomy 12 and del(13q14) and 6 had a normal karyotype. Three patients showed a high risk karyotype: all of them had del(11q). None of the patients had a 17p deletion. Nineteen pts were studied for IGHV mutational status (83%), 12 had unmutated while 7 had mutated IGHV genes. Twenty-one patients were evaluable for response to treatment. The median number of Chl and RTX cycles administered in the 21 patients who completed the treatment protocol was 8 (range 6 to 8 cycles) and 6 (range 4 to 6 cycles) respectively. The median total dose of Chl administered during the treatment was 600 mg per patient (median dose 85 mg each cycle). The median dose of RTX administered was 4000 mg per patient (median dose 710 mg each cycle). Among 21 pts evaluable for response, the Overall Response Rate (ORR) was 76%. Six pts (28%) obtained a complete response, 10 pts (48%) obtained a partial response. No significant statistical differences were noticed in terms of ORR for age more or less than 70 years, fitness status, bulky disease, cytogenetic risk abnormalities or IgVH, ZAP-70 and CD38 categories. On an intention to treat basis the median PFS was not reached at a median time of 21 months (range 2–45). Eleven pts experienced progression after treatment at a median time of 20 months (range 2–36). No significant statistical differences were found among the analyzed risk groups. After a median time of 25 months (range, 2–45 months), TTR was not reached. No significant statistical differences were noticed between the Unmutated and Mutated IgVH groups and for ZAP-70 and CD38 categories with respect to TTR. At present the median follow-up is 29 months, with an OS rate of 80% (19/23). None of the risk factors analyzed were found to influence significantly the OS. In conclusion, this study suggests that the combination Chl-R is a safe and effective therapeutic option for untreated B-CLL pts that are not eligible for fludarabine treatment because of age and/or comorbidities. A multicentre trial to confirm these data is planned. Disclosures: No relevant conflicts of interest to declare.

Outcome of Patients with CML Treated with Dasatinib or Nilotinib after Failure of Second Prior TKIs

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2294-2294
Author(s):  
Antonella Russo Rossi ◽  
Massimo Breccia ◽  
Fausto Castagnetti ◽  
Luigiana Luciano ◽  
Antonella Gozzini ◽  
...  
Keyword(s):  
Median Time ◽  
Conflicts Of Interest ◽  
Cell Uptake ◽  
Second Line ◽  
The Third ◽  
Line Therapy ◽  
Third Line ◽  
New Mutations

Abstract Abstract 2294 Background. The TKIs Nilotinib and Dasatinib offer additional therapeutic options for patients with CML who are resistant or intolerant to Imatinib. These agents, active against the majority of Imatinib resistant BCR-ABL mutated clones, have a different pattern of kinase target selectivity, pharmacokinetics parameters, cell uptake, efflux properties and adverse events profiles. Preliminary results suggest that some patients may respond to a second TKI used as third line therapy, but little is known about the long term benefit of such an approach.Aim of this collaborative Italian study was to verify the response (rate and duration) and the clinical outcome in patients with CML treated with a third TKI after sequential failure of the previous ones. Methods. We evaluated 66 patients with CML, resistant/intolerant to Imatinib and treated with Dasatinib or Nilotinib, then switched to a third- line TKI after treatment failure. Of these, 29 patients were treated with dasatinib after imatinib/nilotinib failure and 37 with nilotinib after imatinib/dasatinib failure. Patients were monitored with complete blood counts, cytogenetic analysis, bone marrow aspiration RT-PCR and mutational analysis. Results. A total of 66 patients (median age 63 years, range, 33–85 years) were treated with sequential TKIs; 40 (61%) patients had received interferon-a before starting Imatinib; 26 (39%) patients received imatinib as first line therapy. The median time on imatinib therapy was 47.5 months (range 4–101 months). At the start of nilotinib as second line, 27/29 (93%) patients were in CP, 1 (3.5%) in AP, and 1 (3.5%) in BP. 9 patients (31%) had developed mutations before starting treatment. The median time on second line TKI was 8 months (range 2–36 months). In the resistant patients 4 new mutations were identified (F359V in two patients, T315I, Y253H+F359V). At the start of dasatinib as second line, 33/37 (89.2%) patients were in CP, 4 (10.8%) in AP. 7 patients (18.9%) had developed mutations before starting treatment. The median time on second line TKI was 14 months (range 4–59 months).In the resistant patients 5 new mutations were identified (F137L in three pts, M318T, M244V+F317L). At the start of the third TKI, 60/66 (90.9%) patients were in CP, 5 (7.6%) in AP, and 1 (1.5%) in BP. Of these, 7 patients (18.9%) on dasatinib and 7 (24.1%) on nilotinib had mutations before starting treatment. The best response to the third line treatment with TKI was 10 (15.2%) MMR, 10 (15.2%) CCyR, 8 PcyR (12.1%), 5 (7.5%) mCyR, 24 (36.4%) CHR and 9 (13.6%) No Response (NR). In the dasatinib group, 9 (31%) patients discontinued treatment because of toxicity versus 17 (45.9%) patients in the nilotinib group.Two new mutations (F317L, E255V) emerged with dasatinib as third line therapy.After a median follow up of 13 months (range 2–37 months) 50 patients (48 CP, 2 AP) are continuing therapy (33 on nilotinib, 17 on dasatinib).Since the start of the third TKI, 61 patients (92.4%) are still alive for a median overall survival of 110 months (range 15–300) (52 CP, 7 AP, 2 NA); the 5 deaths (7.6%) were caused by disease progression and spread of the gene mutation T315I. Discussion. In our study, about one third of patients derived benefit from the use of three sequential TKIs; patients with better, longer response (28.7%) to third TKI were the same patients with a better response to the Imatinib and 2TKIs therapy. All these patients had taken interferon therapy before the Imatinib. In this subset of patients (good responders: CCyR and MMR) 5 patients developed mutations that were sensitive to the sequential treatment.The lack of a durable cytogenetic remission could be explained by the emergence of new kinase domain mutations as patients are exposed to sequential TKI; a change of therapy resulted in an adequate response. In our series, patients with poor prognosis showed mutations not sensitive to the TKIs treatment. Conclusions. Although allogeneic SCT is the treatment of choice in all patients failing 2 TKIs who are suitable candidates for this approach, alternative strategies are required for ineligible patients. The use of a third TKI after failure of two previous TKIs induces response in some patients. Longer follow up of a larger series of patients is needed to determine the long term impact of the response. Disclosures: No relevant conflicts of interest to declare.

Long-Term Remission (>3 years) after Rituximab Monotherapy Used for Patients with Relapsed Indolent Non-Hodgkin Lymphomas (NHL)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1709-1709
Author(s):  
Anne-Sophie Michallet ◽  
Florence Beckerich ◽  
Fadhela Bouafia-Sauvy ◽  
Daniel Espinouse ◽  
Gilles Salles ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Complete Response ◽  
Bulky Disease ◽  
Entire Cohort ◽  
The Subject ◽  
Disseminated Disease ◽  
Question Today ◽  
Term Response

Abstract Background: Rituximab has demonstrated significant clinical efficacy in the treatment of NHL, particularly in combination with chemotherapy, and its use has dramatically changed the treatment and outcome of both indolent and aggressive B-cell NHL over the past decade. Furthermore, consistent toxicity data have been obtained with a safe and tolerable profile in a large majority of patients. Aim: The objective of this retrospective study is to evaluate the long-term efficacy of rituximab monotherapy (4 weekly infusion at induction followed by 4 infusion every 2 months as consolidation) used for patients with relapsed indolent NHL. Results: From May 1998 through January 2011, Among 919 patients with indolent NHL treated in our department, 488 (53%) relapsed and were treated with rituximab alone (first and later relapse). 126 (26%) responded and were still in response 2 years later. These 126 patients (68 (54%) males and 58 (46%) females with a median age of 61 y; range: 17-94) are the subject of our analysis. 24% were over 70 years old, 45% were in first relapsed and 25% in later relapsed. Only 16% of the population have more than one co-morbidities (cardiac and or renal respectively); 79% a normal PS (0-1) with only 4 patients having a PS >2; 80% no bulky disease but 72% a disseminated disease (73% stage III and IV). In this study, 60 (48%) patients had a follicular lymphoma with 50% at an intermediate risk group according to the FLIPI score ; 20 (16%) a marginal zone lymphoma, and 43 (34%) a small lymphocytic or lymphoplasmacytic lymphoma and 3 patients other characteristics of lymphoproliferative disorders. After rituximab monotherapy, 55% of the entire cohort was in complete response (CR) and 31% in CRu or partial response and 5% in stable disease. Among these 126 patients, 74% progressed later than 3 years (38% later than 5 years). With a median follow-up of 6.5 years, 4-year and 8-year PFS were 70% and 30%, respectively. 18% had transformation into Richter syndrome and 12 patients have died. Conclusion: Rituximab monotherapy is an effective therapy in selected relapsed indolent NHL and allows long-term response. This strategy could be used as “spare of chemotherapy” which is an important question today, especially in indolent not curable disease. Disclosures No relevant conflicts of interest to declare.

Pegylated liposomal doxorubicin and platinum in patients with advanced ovarian cancer in late relapse (>6 months)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15035-15035
Author(s):  
L. Wei ◽  
C. Chen ◽  
C. Huang ◽  
S. Chien ◽  
Y. Huang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Median Time ◽  
Advanced Ovarian Cancer ◽  
Pegylated Liposomal Doxorubicin ◽  
Complete Response ◽  
Ca 125 ◽  
Cross Resistance ◽  
Late Relapse ◽  
Open Label ◽  
Overall Response

15035 Background: Platinum and doxorubicin have different mechanisms of action, show no cross-resistance, and their toxicities do not overlap. Because pegylated liposomaI doxorubicin (Lipo-Dox was manufactured by TTY Biopharm Company Ltd. in Taiwan) appears to be a promising form of delivering doxorubicin with decrease of some of the most problematic toxicities, a combination with platinum should be assessed. Methods: An open-label, non-comparative, single center phase II clinical trial. Eligible patients must have histologically proven advance ovarian cancer with two-dimensioned measurable disease or evaluable disease (defined as CA-125 ≥ 40 U/ml), who have been treated with one or two previous platinum- and taxane-based regimen. All patients will hospitalize for 24 hours for treatment. The dose of platinum is fixed (cisplatin at 75 mg/m2 or carboplatin at AUC=5) on D1 and the initial dose of pegylated liposomaI doxorubicin (Lipo-Dox) is 35 mg/m2 on D2 at a 4-week interval. Results: Twenty patients were enrolled from July 2002 to January 2004 and follow up until June 2004. All eligible patients are assessable for response and toxicity. The overall response rate was 80%. Of the 20 patients eligible for response evaluation, 10 (50%) patients had a complete response, 6 (30%) had partial response, 3 (15%) were with stable disease, and 1 (5%) showed progressive disease. An overall response (OR) was achieved in 80% of patients. In patients achieving an OR based on WHO criteria, median CA125 levels declined from 142 U/ml (range, 13–3670 U/ml) during the baseline to 26.5 U/ml (range, 5–375 U/ml) during the last cycle. Median time to response was 65 days (range, 12–188 days). Median duration of response was 471 days (range 146–1085 days). Furthermore, the median time to progression was 481 days (range, 138–1136 days). The main toxicity was myelosuppression, with grade 3 and 4 neutropenia in 3 patients, anemia in 4 patients, and leukopenia in 2 patients. Conclusions: Based on effectiveness and toxicity advantages, the combination of pegylated liposomaI doxorubicin (Lipo-Dox) and platinum should be considered in patients with advanced ovarian cancer in late relapse. No significant financial relationships to disclose.

scholarly journals Omalizumab: Efficacy and Safety in Mast Cell Disorders

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4280-4280
Author(s):  
Richard Lemal ◽  
Guillemette Fouquet ◽  
Louis Terriou ◽  
Mélanie Vaes ◽  
Cristina Livideanu ◽  
...  
Keyword(s):  
Mast Cell ◽  
Median Time ◽  
Safety Profile ◽  
Conflicts Of Interest ◽  
Neuropsychiatric Symptoms ◽  
Treatment Options ◽  
Complete Response ◽  
Effective Treatment Option ◽  
Best Response ◽  
Cell Disorder

Abstract Background. Patients with mast cell diseases may suffer from various distressing symptoms, which can be insufficiently controlled with available therapies, severely affecting quality of life. There is thus a need for new and safe treatment options for these patients. Objectives. We aimed to evaluate safety and efficacy of omalizumab administration in patients with a systemic mast cell disorder. Methods. We included 56 patients with a systemic mast cell disorder who received omalizumab treatment between January 2015 and December 2017, after a pluridisciplinary review at the French National Reference Center for Mastocytosis (CEREMAST). Results. A complete response was achieved for 1 patient (1.8%), a major response for 30 patients (53.6%) and a partial response for 12 patients (21.4%), resulting in an overall response rate of 76.8% (43/56 patients). The response was persistent at least 3 months in 33 patients (58.9%). Median time to first response was 2 months and median time to best response was 6 months. Omalizumab was dramatically effective on all superficial and general vasomotor symptoms and on most gastrointestinal or urinary symptoms, and partially effective on most neuropsychiatric symptoms (Figure 1). Safety profile was acceptable, except for one severe adverse event (cervical edema and dyspnea after the first injection of omalizumab). Side effects were reported in 16 patients (28.6%), mainly of low to mild intensity, yet causing interruption of treatment in 6 patients (10.7%). Conclusion. Omalizumab is an effective treatment option in systemic mast cell disorders, and displays a favorable safety profile. Prospective studies remain necessary to confirm these encouraging results. Disclosures No relevant conflicts of interest to declare.

Efficacy and Safety of 5-Azacytidine Based Regimens in Old AML patients: a Retrospective Study of 29 Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4148-4148
Author(s):  
France Roszkiewicz ◽  
Berengere Gruson ◽  
Ioana Vaida ◽  
Gandhi Damaj ◽  
Bruno Royer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Retrospective Study ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Complete Response ◽  
Newly Diagnosed ◽  
Overall Response ◽  
Co Morbidity ◽  
Significant Difference ◽  
Wbc Count

Abstract Abstract 4148 Background 5-azacytidine (AZA) is an hypomethylating drug. The international multicenter AZA-001 trial established that AZA significantly improves overall survival (OS) in patients with high risk myelodysplastic syndromes (MDS) compared with conventional care regimens (Fenaux, Lancet Oncol 2009). Some recent reports have raised the question of a possible efficacy of AZA in selected patients with acute myeloid leukaemia (AML). In this study we retrospectively analysed the safety and efficacy of a 7 days-schedule of AZA alone or in combination with an HDAC inhibitor, Valproic acid (VA) and with All-trans retinoic acid (ATRA) in patients with newly-diagnosed and refractory/relapsed AML not eligible for intensive chemotherapy. Patients and Methods A monocentric retrospective study from October, 2006 until March, 2009 analysed 29 patients with AML. Among these patients. There were 11 males and 18 females, median age 70,8 years (range 51,2-84,1), AML de novo in 15 patients (3 relapse) and secondary in 14 patients (2 post MPD and 12 post MDS). Median WBC count was 2,5 (range 0,7-140).109/L, 4 patients had WBC more than 10.109/L. The median rate of bone marrow blasts is 30%. 12/27 (44%) patients and 15/26 (56%) have respectively an intermediate and poor risk caryotype. Fifteen (54%) were newly-diagnosed patients, 14 (46%) were refractory/relapsed patients. Median co morbidity index (Sorror, J Clin Oncol 2007) of patients is 2 (0-7). Patients received daily AZA 75mg/m2 J1-J7, ± VA 35 to 50 mg/kg J1-J7 and ATRA 45mg/m2 J8-J28 every 4 weeks. Results 5 azacytidine was used alone for 6/29 (21%) patients and in combination with VA and ATRA for 23/29 (79%) patients. Compliance to the planned therapy was good. Average number of AZA administration was 6 days. To date a total 150 treatment-cycles with a median of 5 cycles/patient were applied (1-14). Treatment was well tolerated. Neutropenia grade3III and thrombopenia grade3III occurred respectively in 26/150 cycles (17%) and in 31/150 (20%). Infections grade3III were observed in 14/150 cycles (9,3 %). Overall response was 62% (17/29): 9 complete response (CR=31%), 3 partial response (PR=10%), 5 haematological improvement (HI=21%), There were 2 stable diseases (SD=7%). 28% of responses were obtained after 1 cycle, 56% after 3 and 89% after 4. Median overall survival (OS) was 13,2 months (0.3-26). We did not observe any significant difference on OS regarding: age, cytogenetics, de novo vs secondary AML, newly diagnosed vs refractory/relapsed patients. OS for patients with SD was similar to patients with CR, PR or HI. WBC >10.109/L before treatment was not correlated with a shorter survival (7.73 months vs 13.2 months p=0,6). Correlation was found between OS and clearance of the creatinine (p=0.005). In conclusion, AZA based regimens seems well tolerated and an effective treatment in AML, with an overall response of 62% and an OS of 13,2 months. A minimum of 4 cycles of treatment is necessary to evaluate the efficacy. OS of patients achieving CR, PR or HI is not significantly different of those with SD. Treatment should be continued until progression of the disease. Disclosures: No relevant conflicts of interest to declare.

Autologous SCT In Patients (pts) with Chemotherapy-Resistant Diffuse Large B Cell Lymphoma (DLBCL) Followed by Maintenance with Rituximab.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4598-4598
Author(s):  
Rodolfo Calixto ◽  
Mauricio Ostronoff ◽  
Fabiana Ostronoff ◽  
Alexandre Sucupira ◽  
Djenane Manso ◽  
...  
Keyword(s):  
B Cell ◽  
Median Time ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Conditioning Regimen ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
Bulky Disease ◽  
Pseudomonas Infection ◽  
Neutrophil Engraftment

Abstract Abstract 4598 There are few data on the use of maintenance Rituximab after auto-SCT for patients with B cell lymphoma of aggressive histology that are resistant to chemotherapy. From May 2005 to March 2010, 25 consecutive pts underwent auto-SCT for DLBCL resistant to chemotherapy at our center. Median age 43 year (7 – 69 yrs); 11 patients were male. Two pts were HIV positive. Initial staging was II-B in 6 patients, II-EB in 4 patients, III-B 8 patients and IV-B in 7 patients. Initial IPI score was low-intermediate (13% of the pts), high-intermediate (58%) and high (29%). Nine of the 25 pts had bulky disease and 8 had visceral or bone marrow lymphomatous involvement. The median time from diagnosis to auto-SCT was 21 months (13 – 48 m). Prior to auto-SCT, 44% of the patients received 2 chemotherapy regimens and 56% received more than 2. All pts had chemotherapy-sensitive disease to the their last chemotherapy regimen prior to auto-SCT, with 80% and 20% of the pts achieving complete and partial remission prior to transplant, respectively. Sixteen out of 25 pts received Rituximab prior to auto-SCT; of those, 5 received Rituximab in the first line chemotherapy and 11 received it as part of the rescue chemotherapy regimens. The protocol was approved by our institutional review board and informed consent was obtained from each pt and or their guardians. Conditioning regimen consisted of Cyclophosphamide 1500 mg/m2 (D-6 to D-3), Etoposide 400 mg/m2 (D-6 to D-3) and Carmustin 150 mg/m2 (D-6 to D-4). The median CD34+ cells/kg infused was 2.9 × 106/Kg (1.9 - 8.5×106). All pts received G-CSF 10 micrograms/Kg/day SC from day +1 until neutrophil engraftment. Median time to neutrophil engraftment (ANC >500/mm3) was 8 days (5 – 17 d). Median time to platelet recover (>20,000/mm3) was 13 days (7 – 29 d). Transplant related mortality at day +100 was one in 25 pts (4%); this pt died due to multi-drug resistant Pseudomonas infection on day +17. Rituximab 375mg/m2 weekly for 4 weeks was administered as maintenance for a total of 4 cycles (16 doses); the cycles started on days +120, +240, +360 and +480 after auto-SCT. Twelve pts developed mild infusion reaction (tremor and rash). The hematological toxicity was low; grade II neutropenia occurred in 9 out of 25 pts. The neutropenic only occurred after the forth dose of the cycle with a median duration of 5 days (2 - 13). All pts received Bactrim and Acyclovir prophylaxis for one year after the auto-SCT. There were no viral infectious complications. Four of the 25 pts died (16%); one due to Pseudomonas infection; 3 due to relapsed disease which occurred at 6, 9 and 19 months after the transplant. Overall disease free survival was 75% with a median follow up of 31 months (6 - 55 mo). Of the five pts with refractory disease who had received Rituximab at some point prior to transplant, 2 pts relapsed and died due to refractory Lymphoma after the transplant, but 03 are alive in CR (9, 13, 21 months). Our data suggests that the administration of Rituximab as maintenance after auto-SCT for pts with DLBCL is well tolerated and it may decrease the incidence of relapse. Randomized studies are warranted to confirm the benefit of Rituximab as maintenance in the post auto-SCT setting to decrease relapse rate. Disclosures: No relevant conflicts of interest to declare.

Complete Response (CR) to Induction Therapy in Patients (pts) with Myc+ and Double Hit Non-Hodgkin's Lymphoma (NHL) Is Associated with Prolonged Progression-Free Survival (PFS).

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2693-2693
Author(s):  
Jonathon B. Cohen ◽  
Susan Geyer ◽  
Gerard Lozanski ◽  
Weiqiang Zhao ◽  
Nyla A. Heerema ◽  
...  
Keyword(s):  
B Cell ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Front Line ◽  
Ki 67 ◽  
Bulky Disease ◽  
Factors Associated ◽  
Line Therapy ◽  
Double Hit

Abstract Abstract 2693 Background: Aggressive B-cell NHL harboring a c-MYC rearrangement (myc+) with or without t(14;18) is associated with shortened PFS and overall survival (OS) (Savage, Blood 2009; Johnson, Blood 2009). Clinical presentation, risk-assessment, and therapies vary among pts and institutions. We reviewed pts with myc+ and double hit NHL treated at the Ohio State University (OSU) from Aug 2008-Jan 2012 to determine factors associated with prolonged PFS and OS. Methods: Pts with de-novo B-cell NHL who were myc+ by FISH break-apart probe were included. Pts with Burkitt's, follicular, and transformed NHL were excluded. Most pts were also evaluated for presence of t(14;18) by FISH, and those myc+ pts with t(14;18) were classified as double hit NHL. Response was determined by PET/CT at the completion of first-line therapy. Associations between myc+ and clinical characteristics were described. PFS and OS were defined from date of diagnosis to date of relapse or death. Univariable and multivariable Cox regression models were performed to assess relationships of selected clinical variables with PFS and OS. Results: Of 49 myc+ pts, 55% were male, and median age at diagnosis was 62 (range: 23–83). Morphologically, 30 pts had diffuse large B-cell lymphoma (DLBCL), 10 pts had B cell lymphoma unclassifiable with features intermediate between diffuse large B cell and Burkitt lymphoma (BCLU), and 9 pts had high grade NHL not otherwise specified. Twenty-eight pts had ECOG performance status ≤1, and 40 pts had stage III-IV disease. Twelve pts had bone marrow involvement, and 26 pts had bulky disease ≥5cm. IPI was ≥3 in 24 pts, and median Ki-67 was 90% (range: 45–100). Twenty-nine of 43 assessed pts (67%) were positive for t(14;18). Therapies included R-CHOP (N=17), R-EPOCH (N=17), Burkitt's-like (ie, R-HyperCVAD, R-CODOXM/IVAC, or R-CHOP with high dose methotrexate; N=11), or other (N=4). No pts underwent autologous transplant in first remission. Twenty-nine pts (59%) achieved a complete response (CR), 2 pts had a partial response, 1 pt had stable disease, 8 pts had progressive disease (PD), and 9 pts died before response assessment (5 pts after cycle 1, 3 pts after cycle 2, and 1 pt after cycle 3). With a median follow-up of 26.2 months (mos; range: 4.8–45.0), the median PFS for all pts was 16.6 mos (95%CI: 9.6 - not reached=NR), and median OS was 37.7 mos (95%CI: 15.7–NR). Median PFS was 3.9 mos for pts without CR vs. not yet reached in pts with CR (p<0.00001). Median OS was 7.0 mos for pts without CR vs. not yet reached for those with CR (Figure 1A; p<0.00001). CR pts were treated with R-CHOP (N=12), R-EPOCH (N=9), Burkitt's-like (N=6), or other (N=2). Four of the CR pts have relapsed at 6, 9, 11, and 17 mos, and 25 CR pts remain in remission at a median follow-up of 27.5 mos (range: 4.8 – 45). Of 3 pts with PR or SD, 2 pts progressed at 3 and 11 mos, and 1 PR pt was lost to follow-up at 15 mos. Of 21 pts who have died, 3 had CR. Median PFS and OS were 8.0 and 12.5 mos, respectively, in double-hit pts (myc+ with t(14;18)) vs. median PFS and OS not yet reached in pts who were myc+ without t(14;18) (p=0.04 for PFS; p=0.05 for OS). Additional factors associated with shortened PFS in univariable analysis included IPI ≥3 (p=0.0001), age ≥ 60 (p=0.046), and presence of B-symptoms (p=0.025). Morphology (DLBCL vs. BCLU), therapy received, Ki-67, and presence of bulky disease ≥5cm were not significantly associated with PFS or OS. In multivariable analysis, CR was independently associated with increased PFS (p=0.0036) and OS (p=0.008; Figure 1B), while t(14;18), morphology, front-line therapy, IPI, bulky disease, age, or presence of B- symptoms were not independently associated with PFS or OS. While increased IPI (p=0.00034) and B-symptoms (p=0.04) were associated with a failure to achieve CR, morphology and therapy were not. Conclusion: While myc+ NHL, with or without t(14;18), has historically been associated with inferior PFS and OS, achievement of a CR with front-line therapy was indicative of a favorable PFS and OS vs. those who do not achieve CR. Additional evaluation of myc+ aggressive NHL is needed to characterize pre-treatment factors associated with achievement of CR and to further evaluate the association of CR to induction therapy with survival outcomes. Disclosures: No relevant conflicts of interest to declare.

Outcome Of Hematopoietic Cell Transplantation (HCT) In Pediatric Patients With Hodgkin Lymphoma (HL): Single Institution Results From Saudi Arabia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5530-5530
Author(s):  
Hassan A Sumaili ◽  
Asim F Belgaumi ◽  
Amani A Al-Kofide ◽  
Amal Al-Seraihy ◽  
Hassan El-Solh ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Progressive Disease ◽  
Pediatric Patients ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Complete Response ◽  
Allogeneic Bone ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Abstract Most pediatric patients with Hodgkin lymphoma are cured of their disease with standard combined-modality first-line therapy. Those who relapse are subjected to salvage chemo-radiotherapy, and patients who respond often undergo either autologous or allogeneic HCT, with a reported outcome ranging from 40%-60%. Variables affecting the outcome of such patients are not clearly defined. This study retrospectively reviewed the clinical characteristics and outcome of patients who underwent HCT at our institution. Between 1995 and 2012, 29 pediatric (age <14 years) patients with HL underwent HCT. This cohort included 24 boys and 5 girls. Their median ages at initial diagnosis and at HCT were 9.85 years (mean 8.85; range 3.6-13.75) and 12.18 years (mean 11.24; range 5.6-14.9), respectively. 28 patients had classic HL (23 nodular sclerosis, 3 mixed cellularity, 1 lymphocyte-depleted, and 1 lymphocyte-rich) and one patient had nodular lymphocyte-predominance HL. Ten had persistent/progressive disease following first line therapy, while 19 had relapsed following achievement of complete response (CR). For these patients median time to relapse from completion of first-line therapy was 16.9 months (mean 20.1; range 1.9-53.1). All patients received salvage chemotherapy and/or radiotherapy prior to HCT; fifteen patients achieved CR, 13 had a partial response and one had progressive disease. Two patients had allogeneic bone marrow (BM) grafts from matched-related donors, while the rest had autologous grafts (16 BM; 10 PBSC; 1 BM+PBSC) following chemotherapy-based myeloablative conditioning. Twelve patients have relapsed/progressed post-HCT at a median of 6.04 months (mean 11.8; range 1.02-71.4). Nine patients have died; eight because of disease progression and one due to sepsis post HCT. Only two patients died within the first 100 days post HCT, giving a Day-100 mortality rate of 6.8%. Two patients who relapsed after HCT were salvaged with chemo/radiotherapy and remain disease free 2.8 and 9.7 years later. The 5-year estimated overall survival (OS) from HCT for the whole cohort is 61.6%, with an event free survival (EFS) of 57.9%. Patients who had persistent/progressive disease at the end first-line therapy or relapsed <6months off therapy had a worse OS and EFS as compared to those who relapsed later (OS 42.9% v. 75.3%, p=0.047 [Taron-Ware]; EFS 41.7% v. 60.8%, p=0.052 [Taron-Ware]). The outcome of patients with relapsed/refractory HL following HCT is encouraging, as a majority of patients survive free of their lymphoma. Timing of relapse/progression remains an important prognostic factor and patients who fail early may be considered for novel therapeutic approaches. Disclosures: No relevant conflicts of interest to declare.

scholarly journals CHLORAMBUCIL PLUS RITUXIMAB AS FRONT-LINE THERAPY IN ELDERLY/UNFIT PATIENTS AFFECTED BY B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA: RESULTS OF A SINGLE-CENTRE EXPERIENCE.

2013 ◽  
Vol 5 (1) ◽  
pp. e2013031 ◽  
Author(s):  
Luca Laurenti ◽  
Barbara Vannata ◽  
Idanna Innocenti ◽  
Francesco Autore ◽  
Francesco Santini ◽  
...  
Keyword(s):  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Front Line ◽  
Prior Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Single Centre Experience ◽  
Unfit Patients ◽  
Grade 3 ◽  
Dose Delay

Currently standard first line therapy for fit patients with B-CLL/SLL are fludarabine-based regimens. Elderly patients or patients with comorbidities poorly tolerate purine analogue-based chemotherapy and they are often treated with Chlorambucil (Chl). However, complete response (CR) and overall response (OR) rates with Chl are relatively low. We now investigated whether the addition of Rituximab to Chl will improve the efficacy without impairing the tolerability in elderly and unfit patients. We included in our study 27 elderly or unfit patients that had not received prior therapy. All patients were treated with Chl (1mg/Kg per 28-day cycle for 8 cycles) plus Rituximab (375 mg/m2 for the first course and 500 mg/m2 for subsequent cycles until the 6th cycle). We obtained an OR rate of 74%. The most frequent adverse effect was grade 3-4 neutropenia, which occurred in 18.5% of the patients. Infections or grade 3-4 extra-hematological side effects were not recorded. None of the patients required reduction of dose, delay of therapy or hospitalization. Overall, these data suggest that Chl-R is an effective and well tolerated regimen in elderly/unfit patients with CLL.

scholarly journals Pediatric Hodgkin’s Lymphoma: 5-Year Experience at Single Center in Pakistan

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5455-5455
Author(s):  
Shazia Riaz ◽  
Safia Khan ◽  
Farhana Badar
Keyword(s):  
Conflicts Of Interest ◽  
Complete Response ◽  
Developed Countries ◽  
Single Center ◽  
Bulky Disease ◽  
Excellent Outcome ◽  
Pediatric Hodgkin Lymphoma ◽  
End Of Treatment ◽  
Night Sweats ◽  
Pediatric Hodgkin’S Lymphoma

Abstract OBJECTIVES: To review patients’ characteristics and treatment outcome pattern of pediatric hodgkinlympoma in a well funded center in developing country MATERIALS & METHOD: This was retrospective review of data of 301 pediatric hodgkin lymphoma patients up to 18 years of age treated in Shaukat Khanum Memeorial Cancer Hospital & Research Center, Lahore, Pakistan, during 2009 to 2013. RESULTS: Total No. of patients was 301, 81% were male. The median age of studied data was 9 years; ranging from 2 to 18 years. B symptoms in the form of fever, weight loss and night sweats were found in 51%, 29% and 34%, respectively. Median stage was 3 with neck bulky disease in 28% and Medistinal widening in 18% of patients. Trend of histopathology was mixed cellualrity at 56.5%. Most common treatment regime was ChlVPP/ABVD (59.5%); 30.6% of these 301 patient also got radiotherapy. At the end of treatment complete response was reported in 76.5%; 11.3% of these were relapsed afterward. CONCLUSION: Our data shows excellent outcome of pediatric hodgkin lympoma and results are comparable to that of developed countries. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document