Safety and Activity of Intensive Short-Term Chemoimmunotherapy in HIV-Positive (HIV+) Patients (pts) with Burkitt Lymphoma (BL)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2692-2692
Author(s):  
Marta Bruno Ventre ◽  
Giovanni Donadoni ◽  
Alessandro Re ◽  
Michele Spina ◽  
Chiara Cattaneo ◽  
...  
Keyword(s):  
Haematological Toxicity ◽  
Tolerability Profile ◽  
High Dose ◽  
Induction Phase ◽  
Short Term ◽  
Bulky Disease ◽  
Septic Complications ◽  
Pilot Experience ◽  
Ecog Ps

Abstract Abstract 2692 BACKGROUND: Worldwide experience with intensive chemotherapy plus HAART in HIV+ pts with BL is still limited. In a few available studies, this strategy was associated with complete remission (CR) rates of 70–80% and 2-year overall survival (OS) rates of 45–70%, but with a treatment-related mortality of 15–20%, mostly due to septic complications. We adapted an intensive short-term chemotherapy program used for HIV-negative childhood and adult pts with BL [Di Nicola M, et al. BJH 2004] to treat HIV+ pts with maintained efficacy and lower toxicity. Herein, we report feasibility and activity of this program addressed in a multicenter pilot experience. METHODS: Consecutive HIV+ pts with BL, age ≤65 yrs and ECOG-PS ≤3 were treated with an intensified program at three Institutions. The program included a 38-day Induction Phase (IP) of sequential doses of methylprednisolone, cyclophosphamide, vincristine, rituximab, methotrexate, VP-16, and doxorubicin, with intrathecal prophylaxis/treatment. After IP, pts in CR received consolidation phase (CP; cytarabine+cisplatin+rituximab); pts in PR received CP followed by BEAM + ASCT; pts with SD or PD received intensification phase (R-ICEx2 + high-dose cyclophosphamide + high-dose cytarabine + BEAM + ASCT). Leukaphereses were performed after CP. Pts with residual or bulky disease received consolidation radiotherapy. RESULTS: 13 pts (median age 42 yrs, range 27–63; all males; ECOG-PS >1 in 5) were considered. Most pts had advanced stage, increased LDH, B symptoms, bulky lesions, and extranodal disease (meningeal in 2). Eight pts received HAART before BL; median CD4+ cells at BL diagnosis was 272 (range 17–858; 4 pts had CD4+ <200 c/μL). Twelve pts completed IP (median duration 48 days; range 38–54), with some delay in 8 pts (median 3 days, range 1–14); 1 pt died of sepsis (CD4+= 17 c/μL). Dose reductions were not recorded. During the IP, G3-G4 haematological toxicity was observed in all pts: neutropenia in 12, thrombocytopenia in 5 and anaemia in 7. RBC and platelets transfusions were indicated in four and five patients, respectively. With conventional antimicrobial prophylaxis and G-CSF support, 12 pts had infections, with CMV reactivation in 5. Only 1 pt had G4 non-hematological toxicity (transient diarrhea). Response after IP was CR in 6 pts and PR in 5, with an ORR of 85% (95%CI: 66–100%); 1 pt experienced meningeal PD. Per protocol (Fig. 1), the 6 CRs received CP and were referred to follow-up; the 5 PRs received CP followed by BEAM + RT in three pts and by intensification in two pts who experienced PD after CP; the pt who experienced PD after IP was referred to intensification. Overall, 11 pts were referred to CP; the first 4 experienced prolonged G4 neutropenia and infections, including CMV and EBV reactivations; thus, the following 7 pts were treated only with cytarabine-rituximab as CP; none of them experience infectious events. Leukaphereses were successful in 7 of the 9 referred pts. Response after the whole program was CR in 9 pts (CRR= 69%; 95%CI: 44–94%); intensification is ongoing in 2 failed pts and 1 pt died of lymphoma. At a median follow-up of 16 months (range 4–24), none of the 9 pts who achieved CR and completed the whole program experienced relapse; 11 pts are alive (9 in CR), one pt died of BL and one of sepsis, with a 2-year OS of 81%. CONCLUSIONS: This pilot experience suggests that this intensive short-term program is feasible in HIV+ pts with BL. The proposed program shows a better tolerability profile and a similar activity respect to other more demanding and resource consuming regimens. A multicenter prospective phase II trial is warranted. Disclosures: Off Label Use: ofatumumab, in label for CLL.

A GITIL Prospective Randomized Multicenter Phase III Study of High Dose Sequential Chemotherapy with Rituximab (R-HDS) and Autologous Transplantation (ASCT) of Peripheral Blood Stem Cells Versus CHOP and Rituximab Delivered Every 14 Days (R-CHOP-14) in High-Risk Patients with Diffuse Large B-Cell Lymphomas (DLBCL): Interim Analysis on Feasibility and Toxicity (Protocol R-HDS 0305).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1898-1898
Author(s):  
Sergio Cortelazzo ◽  
Atto Billio ◽  
Alessandro Rambaldi ◽  
Corrado Tarella ◽  
Ingnazio Majolino ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Iii ◽  
Control Group ◽  
High Dose ◽  
Advanced Stage ◽  
Bulky Disease ◽  
Free Survival ◽  
High Risk Patients ◽  
Risk Patients ◽  
Ecog Ps

Abstract R-HDS 0305 (Clinical Trials. gov. number NCT00355199) is a multi-centre, unblinded, randomized controlled phase III trial involving 240 patients in 3 years from 16 Italian Cancer Centres, with DLBCL without CNS involvement, advanced stage (stage ≥IIB, bulk), age from 18 to 60 years with ECOG-PS=0–3 and aaIPI=2–3 or age from 61 to 65 years with ECOG-PS=0–2 and IPI 3–5. The control group received R-CHOP-14, which comprised 8 courses of chemotherapy every 14 days, supported by GCSF (day 7–11)±IFRT, if they achieved at least a PR after 4 cycles. Cases refractory to R-CHOP-14 were given R-HDS as salvage therapy. Experimental arm consisted in a R-HDS program, including a debulking phase of 3 courses of doxorubicin-containing chemotherapy (APO), followed by high-dose (HD)-cyclophosphamide (CTX) 7g/sqm, HD-Ara-C (2 g/sqm every 12 hours for 6 days), HD-etoposide 2g/sqm+Cisplatin 100 mg/sqm. After HDS chemotherapy, HD-mitoxantrone plus melphalan (60 and 180 mg/sqm) or a BEAM (BCNU 300 mg/sqm, etoposide 200 mg/sqm, Ara-C 4000 mg/sqm, L-PAM 140 mg/sqm) conditioning regimen with ASCT±IFRT was planned. Rituximab (375 mg/sqm) is given for a total of 6 doses, twice after HD-CTX and HD-Ara-C, as in vivo purging before CD34+ cells harvest, and twice after ASCT. The primary outcomes of the study are complete remission and disease-free survival, overall survival, event-free survival and toxicity. From July 2005 to July 2007, 89 patients were enrolled in the study (R-CHOP-14=43; R-HDS=46). The median age was 51 (range 19–65 years), 11 (12%) had ≥60 years and the M/F was 1.3. Patients presented with adverse features such as advanced stage (88%), BM infiltration (28%), bulky disease (71%), elevated LDH (84%), poor ECOG-PS (55%) and &gt;1 extranodal sites (59%). Until now only 3 patients (3.4%) were refractory to planned treatment: 1/43 (2%) patients belonging to R-CHOP-14 arm shifted to R-HDS salvage treatment and other 2 patients died from lymphoma progression. The main G 3–4 WHO toxicity was haematological: anemia, granulocytopenia and thrombocytopenia occurred in 8%, 18% and 13% of patients, respectively. Grade 2–3 gastrointestinal toxicity and infectious episodes were recorded in 6% and 9% of patients, respectively. Two patients recovered from acute respiratory distress and 2 died of treatment-related toxicity (2.2%). In conclusion, if the R-HDS trial confirms earlier results, preliminary data show that intensive programs such as dose-dense chemo-immunotherapy and R-HDS with ASCT are feasible until 65 years with an acceptable toxic profile, also on the multi-centre basis. At completion of the trial we will assess the role of R-HDS and ASCT on the outcome of high-risk patients with DLBCL.

Feasability and Toxicity After Induction Treatment with Rituximab-HCVAD and Metotrexate/Citarabine, Followed by Consolidation with Y-90 Ibritumomab Tiuxetan (Phase II GELTAMO–LCM 04-02 study).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1703-1703
Author(s):  
Reyes Arranz ◽  
Ana Garcia-Noblejas ◽  
Carlos Grande ◽  
José Terol ◽  
José Javier Sánchez ◽  
...  
Keyword(s):  
Haematological Toxicity ◽  
Induction Treatment ◽  
Ibritumomab Tiuxetan ◽  
Bulky Disease ◽  
Consolidation Treatment ◽  
Lower Stage ◽  
Ann Arbor ◽  
Grade 3 ◽  
Anti Cd20

Abstract Abstract 1703 Poster Board I-729 Abstract text Background Mantle Cell Lymphoma (MCL) is an entity with a median survival of 2- 4 years, so it is currently considered an aggressive tumour. Standard chemotherapies for other B cell lymphomas have yielded poor results. Better outcomes have been communicated with the use of up front intensive chemotherapy or of high doses schemas with stem cell support as consolidation of the response, although relapses frequently occur. Keeping in mind these considerations, we used the Hyper-CVAD/MTX-AraC squema in association with anti-CD20, followed by consolidation with Ibritumomab-tiuxetan (ZevalinR) with the aim of eradicating minimal residual disease and decrease the risk of relapse. Aims Evaluate the feasibility, safety and, efficacy for overall response, complete response and progression free survival (PFS) in newly diagnosed MCL patients with advanced Ann Arbor stage or with lower stage but with B symptoms or bulky disease. Methods All patients received: Anti-CD20/Hyper-CVAD therapy alternating with anti-CD20/MTX/Ara-C, supported with Peg- Filgastrim. Response was evaluated after 4 cycles and, treatment continued up to a median of 6 cycles if response (complete or partial) was achieved. Consolidation treatment consisted in a single dose of Y90-Ibritumomab-Tiuxetan (Zevalin) (RIT) administered 8 to 12 weeks after the last cycle. We started at a dose of 0.3 mCi/kg with a planned dose escalation to 0.4 mCi/kg if no unacceptable toxicity was observed in the 1st three patients treated. Results From February 2006 until July 2008, 30 patients were enrolled. Patients' characteristics: 77% male, median age of 59 years old (range 41-70), 93.3% Ann Arbor stage IV, 87% bone marrow infiltration, 62% gastrointestinal infiltration and 13%were blastic variant. Induction therapy: The main toxicities over 170 cycles were haematological and greater in the odd cycles (90% vs 53% grade 3-4 Neutropenia and 98% v. 33% grade 3-4 thrombocytopenia). Sixty five SAEs were reported during induction, mainly neutropenic fever and upper tract respiratory infection with 1 death due to sepsis (3.3%), and 5 non-related events (including 1 suicide). Response after induction: 20 patients (66,7%) were in CR, 5 (16,7%) in uRC, 1 (3,3%) progressed, and 4 patients (13,3%) were not evaluable due to early events (2 deaths and 2 toxicities). Consolidation with RIT: dose of RIT was fixed at 0.3 mCi/Kg after treatment of the first 6 patients and total of 18 patients (60%) have finally received it. Grade 3-4 neutropenia and thrombopenia was observed in 72% and 83% of the patients with a median duration of 3 and 8 weeks, respectively. Ten SAEs with no deaths were reported after consolidation. Twelve patients (40%) could not accomplish the whole treatment due to following reasons: 8 because of induction toxicity (5 infection with one death, 1 neurological, 3 delayed haematological recovery); 1 non related death, 1 progression and 1 withdrawal for personal reasons. Survival: With a median follow up of 25 months. Actuarial OS and PFS to 33 months is 90% and 75% respectively. Conclusion treatment of MCL with 6 cycles of Hyper-CVAD/MTX-AraC with anti-CD20 can be accomplished in 70% of the patients up to 70 years, although close follow-up and dose adjustments are frequently required mainly due to haematological toxicity. Consolidation with Ibritumomab-tiuxetan is safe and feasible at a dose of 0,3 mCi/Kg. Efficacy is high with an ORR and PFS of 83% and 75%, respectively although longer follow-up is needed to evaluate the role of consolidation treatment with RIT. Disclosures Salar: Amgen: Honoraria.

Prospective, multicenter, randomized GITMO-IIL trial comparing intensive (R-HDS) to conventional chemoimmunotherapy (CHOP-R) in high-risk follicular lymphoma (FL) at diagnosis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8006-8006 ◽  
Author(s):  
M. Ladetto ◽  
F. De Marco ◽  
F. Benedetti ◽  
U. Vitolo ◽  
C. Patti ◽  
...  
Keyword(s):  
High Risk ◽  
Superior Performance ◽  
Phase Iii ◽  
Bulky Disease ◽  
Absolute Increase ◽  
Intention To Treat ◽  
Secondary Endpoints ◽  
Extranodal Disease ◽  
Ecog Ps

8006 Background: The GITMO-IIL trial evaluated if an intensified treatment with ASCT is better than conventional chemotherapy (both supplemented with Rituximab) in high-risk FL at diagnosis. Methods: Eligibility required a FL with aaIPI>1 or IIL>2 score and an age of 18–60. Primary endpoint was EFS. The analysis was intention to treat. Secondary endpoints were PFS, DFS, OS, rate and prognostic value of MR. R-HDS and CHOP-R have been already described (Ladetto et al ASH 2005, Rambaldi et al Blood 2002). Planned sample size was 240 to detect a 20% absolute increase in the 3-years EFS. However the trial was stopped at 136 pts due to R-HDS superiority in EFS at a planned interim analysis. Cross-over was allowed after CHOP-R failure. Centralized PCR-based molecular analysis was planned on BM cells. Results: Age, stage, LDH, bulky disease, B-symptoms ECOG PS, extranodal disease aaIPI, IIL and retrospectively assigned FLIPI were similar in the two arms. CRs were 59% with CHOP-R and 85% with R-HDS (p<0.001). At a median follow-up of 39 months EFS and PFS are 36% and 38% for CHOP-R and 66% and 72% for R-HDS. OS is 83% in each arm. 67% of relapsed R-CHOP pts underwent R- HDS. MRs were 44% after CHOP-R and 80% after R-HDS (p<0.001). MR was associated to a better PFS (p<0.001). Of note, 3yrs PFS of pts with or without MR was similar in the two arms (MR: 67% with CHOP-R and 76% with R-HDS) (no MR: 25% for CHOP-R and 32% for R-HDS). MR was the strongest independent prognostic factor for PFS, EFS and DFS by multivariate analysis. Conclusions: This is the first phase III trial including MR analysis in a high proportion of pts and comparing intensified versus conventional therapy in the rituximab age. This trial indicates that: a) R-HDS has a better EFS and PFS in truly high-risk FL patients; b) MR is the strongest outcome predictor available in FL; c) the similar outcome in pts achieving (or not achieving) MR, regardless of treatment received, indicates that the superior performance of R-HDS is mostly due to its superior MR rate. [Table: see text]

scholarly journals Real World Outcomes of Patients with Relapsed/Refractory Diffuse Large B Cell Lymphoma Who Are Ineligible for Autologous Stem Cell Transplantation and Receive Commercially-Available Salvage Therapy

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2893-2893
Author(s):  
Emily C. Ayers ◽  
David J Margolis ◽  
Phyllis A. Gimotty ◽  
Daniel J. Landsburg
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
B Cell Lymphoma ◽  
Standard Of Care ◽  
Current Therapy ◽  
High Dose ◽  
Cell Of Origin ◽  
Advisory Committees ◽  
Ecog Ps

Introduction: Salvage immunochemotherapy (IC) followed by high-dose chemotherapy with autologous stem cell transplantation (autoSCT) is standard-of-care second-line therapy (2L) for patients with relapsed or refractory (R/R) diffuse large B cell lymphoma (DLBCL) deemed fit for autoSCT as per the CORAL study (J Clin Oncol. 2010 Sep 20;28(27):4184-90). Optimal therapeutic management of patients with R/R DLBCL who are autoSCT-ineligible is unknown. Here we describe the real-world outcomes of patients with R/R DLBCL who receive palliative intent 2L therapy in community and academic settings and do not receive autoSCT. Methods: This analysis includes de-identified patients from the nationwide Flatiron Health electronic health record-derived database with a histologic diagnosis of DLBCL and R/R disease after frontline IC who do not undergo autoSCT and receive treatment with either bendamustine-based therapy, gemcitabine-based therapy, lenalidomide, or ibrutinib. Patients receiving rituximab/ifosfamide/carboplatin/etoposide (R-ICE) and high-dose cytarabine-containing second-line therapies were excluded. Event free survival (EFS) was defined as the interval between the start of current therapy and start of subsequent therapy if needed, last follow-up on current therapy, or death on therapy. Overall survival (OS) was defined as the time between start of current therapy and death or last follow-up while alive. Results: A total of 250 patients were eligible for inclusion in 2L. Eight patients received autoSCT after gemcitabine therapy and were excluded from this analysis. Clinicopathologic characteristics at time of diagnosis include 56% male, 87% age >60, 55% ECOG performance status >1, 87% stage III-IV disease, 78% IPI >2, 56% germinal center (GCB) of those with cell of origin testing performed, 9% cMYC rearrangement positive when tested, and 29% transformed from indolent disease. A total of 106, 78, 36, and 22 patients received bendamustine, gemcitabine, lenalidomide, and ibrutinib, respectively. For all patients, median EFS was 5.1 months and median OS was 14.3 months in 2L. Median EFS was 7.6, 2.4, 9.1, and 4.2 months, and median OS was 16.0, 9.4, 16.3, and 11 months for bendamustine, gemcitabine, lenalidomide, and ibrutinib in 2L, respectively. Patients receiving bendamustine and lenalidomide demonstrated significantly improved EFS compared to those receiving gemcitabine (p=0.001 and 0.01, respectively), see Figure 1. We observed no difference in EFS (p=0.40) or OS (p=0.89) between lenalidomide and bendamustine in 2L. Univariate analysis demonstrated receipt of gemcitabine, ECOG PS>1, and IPI >2 to have statistically significant increased hazard for treatment failure and ECOG PS>1 to have an increased hazard for death in 2L relative to the reference group. Multivariate analysis demonstrated receipt of gemcitabine (HR 1.57, p=0.03 95% CI: 1.04 - 2.37) and ECOG PS>1 (HR 1.61, p=0.02 95% CI: 1.09-2.38) were associated with an increased hazard for treatment failure in 2L. Median EFS for patients on lenalidomide was 6.7 and 8 months (p=0.26), and median OS was 13.9 and 12.2 months (p =0.48) for patients with nonGCB and GCB cell of origin, respectively. Conclusions: For patients with R/R DLBCL treated with palliative therapy in the 2L, bendamustine- and lenalidomide-based therapies resulted in significantly longer EFS compared to gemcitabine therapy. Although we cannot exclude the possibility that some patients received gemcitabine in 2L with the original intent to proceed with autoSCT, this does not contest our results as this therapy remains inferior to bendamustine and lenalidomide even if given to a potentially more fit patient population. Analysis shows no difference in outcomes by cell of origin if receiving lenalidomide in 2L. These findings may serve as benchmarks for outcomes following receipt of these therapies in the non-investigational setting and suggest both bendamustine and lenalidomide may be considered reasonable standard-of-care therapies for patients unfit for autoSCT in the 2L setting. Figure 1 Disclosures Landsburg: Celgene: Membership on an entity's Board of Directors or advisory committees; Triphase: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Speakers Bureau; Seattle Genetics: Speakers Bureau; Triphase: Research Funding; Takeda: Research Funding; Takeda: Research Funding. OffLabel Disclosure: Outcomes with lenalidomide and ibrutinib in patients with relapsed/refractory DLBCL will be discussed.

Rituximab-supplemented high-dose sequential chemotherapy (R-HDS) has better EFS and PFS than R-CHOP in poor risk follicular lymphoma (FL) at diagnosis: A multicenter randomized GITMO/IIL trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7525-7525
Author(s):  
M. Ladetto ◽  
F. Benedetti ◽  
U. Vitolo ◽  
C. Patti ◽  
A. Rambaldi ◽  
...  
Keyword(s):  
Residual Disease ◽  
Current Data ◽  
High Dose ◽  
Bulky Disease ◽  
Intention To Treat ◽  
Poor Risk ◽  
Sequential Administration ◽  
Extranodal Disease ◽  
Ecog Ps

7525 Background: HDS with ASCT is effective and feasible in FL at the multicenter level and suitable for Rituximab supplementation (R-HDS). This randomized trial compared R-HDS with Rituximab-supplemented CHOP (R-CHOP) in poor risk FL patients (pts) <60 yrs. Methods: Between 2000 and 2005, 136 pts have been randomized (68/arm). Eligibility required age-adjusted IPI ≥2 (125 pts) or, in the absence of this criterion, ≥3 IIL adverse factors (11 pts). Primary endpoint was EFS. Clinical features were: median age 50 yrs (22–60), stage III-IV 98%, elevated LDH 78%, bulky disease 66%, B symptoms 47%, extranodal disease (other than BM) 45%, ECOG PS >1 47%. R-HDS consisted of: i. 2 APO and 2 DHAP; ii. sequential administration of Etoposide 2g/sqm, 2 Rituximab, Cyclophosphamide 7 g/sqm with PBPC collection (in vivo-purged with 2 additional Rituximab); iii. Mitoxantrone (60 mg/sqm) + L-Pam (180 mg/sqm) followed by 5–8 × 106 CD34+ cells/kg. R-CHOP consisted of 6 CHOP courses followed by 4–6 doses of Rituximab. Cross-over was allowed. bcl-2/I gH-based minimal residual disease analysis was planned. Assessement was “intention to treat”-based. Results: Current data are updated at 31/5/05. Next closing date will be April 2006. The two arms were balanced. 68% patients concluded R-CHOP (failures were due to progression 29% and toxicity 3%) and 78% R-HDS (failures due to progression 9%, toxicity 5%, poor mobilization/refusal 8%). Toxic deaths were 4 (2 in each arm); in addition 1 gastric cancer and 1 AML occurred in the R-HDS arm. Progressions and non-responses were 31% with R-CHOP and 11% with R-HDS (p < 0.05) CRs were 58% and 87% respectively. Current median follow-up is 24 months. EFS and PFS at 24 months are 41% and 48% for R-CHOP and 66% and 75% for R-HDS (p < .001). At present OS is similar. Salvage treatment following R-CHOP is currently known in 22 pts: 16 received R-HDS, with 10 achieving CR. Molecular remission, (two PCR-neg BM samples at 6 months intervals), was observed in 54% of R-CHOP and 77% of R-HDS pts Conclusions: R-HDS induces more CRs and has better EFS and PFS than R-CHOP in this rare and aggressive population of high-risk FL patients. These results cannot be extrapolated to standard-risk pts. [Table: see text]

Single-fraction radiosurgery for the treatment of renal cell carcinoma.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 590-590 ◽  
Author(s):  
Michael D. Staehler ◽  
Boris Schlenker ◽  
Alexander Karl ◽  
Annabel Spek ◽  
Alexander Muacevic
Keyword(s):  
Renal Cell Carcinoma ◽  
Renal Function ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Long Term Results ◽  
Tumor Control ◽  
High Dose ◽  
Short Term ◽  
Single Fraction

590 Background: We report on patients with renal cell carcinoma (RCC) who were treated with single fraction high-dose local stereotactic radiosurgery (SRS) using the robotic Cyberknife system to avoid nephrectomy and consecutive hemodialysis. Methods: Fifty-two patients with histologically confirmed RCC and median age of 63.6 years (43.6-86.5) with the indication for renal surgery and highest risk for consecutive hemodialysis were entered into a prospective case control study of single fraction SRS with 25Gy. Tumor response, renal function, survival, and adverse events were estimated every three months with a follow-up of at least six months. Results: R.E.N.A.L. score was low in 1, moderate in 30 and high in 21 patients. 28 patients had singular renal units. Median follow-up was 26.9 months (1.8 - 52.6). Local tumor control nine months after SRS was 98% (95% CI: 89-99%). 43 lesions showed a measurable tumor size reduction including six complete remissions and 33 partial remissions. Renal function remained stable with a median serum creatinine at baseline of 1.10 mg/dl (0.4 -2.0) and 1.11 mg/dl (0.8-2.2) at follow-up. In one patient grade I erythrodermia, in three patients grade I fatigue and in two patients grade I nausea occurred. In all patients nephrectomy was avoided. Conclusions: Single-fraction SRS as an outpatient procedure is a treatment modality with short-term safety and efficacy to avoid treatment-related loss of renal function and hemodialysis in selected patients with RCC. Short term follow up of oncological and functional results so far is excellent. Further studies are needed to determine the limits of SRS in this setting and long term results.

When May Patients Be Considered Cured after Autografting for Hodgkin Lymphoma?.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1909-1909
Author(s):  
Robert M. Dean ◽  
John W. Sweetenham ◽  
Tao Jin ◽  
Stacey Brown ◽  
Brad Pohlman ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Cleveland Clinic ◽  
Disease Status ◽  
Recurrence Risk ◽  
High Dose ◽  
Karnofsky Score ◽  
Bulky Disease ◽  
Post Transplant

Abstract Patients who undergo high-dose chemotherapy with autologous stem cell transplantation (ASCT) for Hodgkin lymphoma routinely undergo surveillance for post-transplant recurrence. Follow-up schedules after ASCT are based largely upon expert opinion rather than data. To formally describe the evolution of recurrence risk over time for Hodgkin lymphoma after ASCT, we used a prospectively maintained database to retrospectively evaluate the outcomes of 245 patients who underwent ASCT for Hodgkin lymphoma at the Cleveland Clinic Foundation from 1985 through 2005. Patient characteristics: male gender in 64%; median age, 34 years (range, 18–70); median time from diagnosis to transplant, 22 months (4–327); Karnofsky score &gt; 80 in 89%; median 2 prior regimens (1–4); prior XRT in 52%; bulky disease &gt; 10 cm in 20%; stage III-IV in 62%; disease status of CR1/PR1 in 8%, CR2/PR2 in 69%, refractory in 11%, other in 12%; preparative regimen of BuCyVP in 65%, CBV in 26%, TBI/others in 9%. Median follow-up after ASCT for all pts was 35 months (0–223); for surviving pts, 74 months (3–223). At 5 years, estimated overall survival and relapse-free survival were 47% and 36%, respectively. Relapse occurred in 115 pts, with 5-year relapse rate estimated at 44% (Figure). Figure Figure Landmark analyses were conducted to estimate long-term outcomes for patients in remission at various times after ASCT, as shown in the Table: Duration of Remission after ASCT Long-Term Likelihood of Continued Remission 1 year 63.8% 2 years 78,8% 3 years 83.0% 5 years 97.0% These data illustrate the declining threat of relapse that faces patients who achieve remission following ASCT for Hodgkin lymphoma. Most patients who are destined to experience disease recurrence after ASCT do so within the first 2 years post-transplant. Patients who remain in remission 5 years after ASCT are at extremely low risk for subsequent relapse and can be reassured that they are likely cured. This analysis provides a factual basis to support gradually decreasing the frequency of surveillance visits and to discontinue routine monitoring for relapse at 5 years after ASCT.

Radioimmunotherapy (90Y-Zevalin®) Combined with BEAM Conditioning Regimen and Autologous Stem Cell Transplantation for the Treatment of Non Hodgkin Lymphomas: Results of An Italian Multicenter Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1144-1144 ◽  
Author(s):  
Vincenzo Pavone ◽  
Anna Mele ◽  
Antonio Rana ◽  
Cosimo Del Casale ◽  
Anna Rita Messa ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Treatment Plan ◽  
Conditioning Regimen ◽  
Haematological Toxicity ◽  
Significant Risk ◽  
High Dose

Abstract Radioimmunotherapy (RIT) with 90Y-Zevalin® combined with high dose therapy and autologous stem cell transplantation (ASCT) is gaing increasing importance for the treatment of relapsed or refractory non Hodgkin Lymphoma (nHL). We evaluated the feasibility and the clinical results of the addition of 90Y-Zevalin® at standard dose to BEAM regimen (Z-BEAM) in nHL pts who failed to achieve complete remission (CR) after previous chemoimmunotherapy. Methods. Between October 2005 and June 2008, 53 patients were enrolled in 11 italian centers. The treatment strategy is shown in figure 1. Salvage treatment consisted of 2 courses of R-DHAP. PBSCs were collected after mobilization with DHAP and G-CSF plus in vivo purging with Rituximab. Patients’ characteristics are shown in table 1. Results. The median CD34+ cells infused was 5.5 x10^6/Kilograms (range 2.55–34). All patients engrafted. The median number of red blood cell and platelet transfusion were 4 (1–7) and 6 (1–8), respectively. The median time to platelet and neutrophil counts higher than 20x10^9/L and 0.5x10^9/L were 14 (range, 9–60 days) and 10 days (range, 8–20), respectively. Mucosites occurred in all pts (grade III in 20 and grade IV in 5 patients). Febrile neutropenia occurred in 39 pts (74%). Eight pneumonitis and 12 blood stream infections, mainly by Gram+, were documented. One patient developed an atrial fibrillation. Five pts were not evaluable for response because too early. The 90-day overall response rate was 86% with 74% of CR. Three relapses (relapse rate 9%) and four progression were documented at a median follow-up of 247 days post Z-BEAM (range, 125–818). The potential factor to predict CR was: at last PR before Z-BEAM (p=0.06). Fourthy patients are alive at a median follow-up of 175 days post HST (range, 6–590): thirty pts in CR (57%), three pts in PR (5.5%), three pts in progressive disease (PD, 6%)(fig. 2). Fourtheen pts died (26%): 5 deaths due to TRM before day 90, 1 for ARDS (+230), 1 TRM post a subsequent RIC allotransplant (+95) and 6 due to PD (median follow-up 110 days, range 97–150). The Kaplan-Meyer estimated 3y-EFS is 64%. Five early deaths before day-90 occurred: 2 due to septic shock (day +6 and +39), 1 to pneumonitis (+22), 1 for BK viral encephalites (+61) and 1 to MOF (+14). The Kaplan-Meyer estimated Treatment Related Mortality (TRM) is 9.3%. Two statistically risk factors for 90-day TRM (p&lt;0.03) were documented: age elderly then 65 and non follicular lymphomas histology. Cox multivariate regression analysis demonstrated that age more than 65 is a significant risk factor for TRM (3.4% in pts aged less then 65 years and 21,05% in older pts; p&lt;0.01). Conclusion. In pts with different histology nHL, who failed to achieve CR after previous immuno-chemotherapy, RIT integrated with high-dose chemotherapy (Z-BEAM) is capable to induce 86% of ORR, 74% of CR and 3 ys EFS of 64%, with sustained engraftment and an acceptable extra-haematological toxicity, mainly restricted to pts older then 65 ys. The power of this program needs to be assessed in a larger series of patients and in a randomized fashion. Table 1: Patient Characteristics and 90-day response post HST Figure. 1 Treatment Plan Figure. 1. Treatment Plan

Primary Female Genital Lymphoma: Prognostic and Therapeutic Considerations

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4941-4941
Author(s):  
Sara Steffanoni ◽  
Alberto Agazzi ◽  
Daniele Laszlo ◽  
Sarah Jane Liptrott ◽  
Mara Negri ◽  
...  
Keyword(s):  
Response Rate ◽  
Early Stage ◽  
Local Treatment ◽  
High Dose ◽  
First Line ◽  
Bulky Disease ◽  
First Line Therapy ◽  
Line Therapy ◽  
Female Genital

Abstract Primary Female Genital Lymphoma (PFGL) is very rare, representing 1.5% of all Non-Hodgkin’s Lymphomas (NHLs) and 0.5% of female genital malignant tumours; uterus is the main commonly genital site involved by NHL. Most PFGLs are B-cell lymphomas; usually they occur in 5th decade of life. Because of PFGL rarity, a standard treatment has not been identified yet. This is a retrospective study on 20 women with PFGL, treated at European Institute of Oncology. The median age was 52 yrs (range 30–79 yrs); at diagnosis 6 pts were asymptomatic, 11 reported pelvic symptoms and 3 B symptoms. According to the International Prognostic Index, 7 pts had low, 6 intermediate, 6 high risk and one pt not known. Eleven pts had uterine involvement, with a concomitant extension to vagina in 5 of them, ovary NHL was recognised in 4 pts, vaginal NHL in 4 pts and vulvar NHL in one pt. Diffuse large B-cell NHL (DLBCL) was diagnosed in 14 pts, marginal extranodal NHL in 3 pts and follicular in 3 pts. According to Ann Arbor staging system: 8 pts were in early stage (IE–IIE) and 12 pts in stage IVE; considering FIGO system: 11 pts were in early stage (I–II), 6 pts in stage III for regional lymph node involvement and 3 in stage IV for concomitant non-genital extranodal localization; 12 pts presented with bulky disease. At diagnosis no pts had bone marrow involvement. The diagnostic biopsy was performed by endoscopy in 13 pts and by ultrasound-guided in 2 pts, whereas 5 pts underwent laparotomy. One pt with vulva-limited marginal NHL did not receive any treatment until disease progression (PD) and transformation to DLBCL. Five pts underwent laparotomy and adjuvant chemotherapy (CT) alone (n=4) or in combination with radiotherapy (RT) (n=1); 14 pts received CT alone (n=8) or in combination with RT (n=6) as first line therapy. Anthracycline-containing CT was delivered to all pts with DLBCL (n=14) and to one pt with high grade follicular NHL, 12 of them received concurrent immunotherapy anti-CD20 (Rituximab). Central nervous system (CNS) chemo-prophylaxis with i.v. high dose methotrexate was delivered to 3 pts because of advanced or bulky disease. Two pts with follicular and 2 with marginal subtype received alkylating-containing CT alone (n=2) or with Rituximab (n=2). The Overall Response Rate (ORR) to first line therapy was 80%; the response did not improve by the addition of local treatment to CT. Three pts did not response to first line therapy: one with marginal NHL in stable disease did not receive any additional treatment because of asymptomatic disease; two with DLBCL in PD underwent salvage treatment with high dose CT and died in PD, concurrent intrathecal therapy was mandatory in one pt because of CNS relapse. Three pts with follicular NHL, in response to first line therapy, relapsed: one went on to receive maintenance Rituximab, one resulted refractory to different rescue CT regimens and died in PD, one underwent autologous bone marrow transplantation obtaining CR. After a median follow up of 51 months (range 11–164 months), 17 pts are still alive: 10 in CR and 7 in PR, 3 pts died in PD. The Overall Survival (OS) at 3 and 14 yrs was 84.8% and 42.4% respectively. According to the literature the most common histological subtype of PFGL occurred in our population was DLBCL and the most frequent genital site involved was uterus (55% of cases) [Lagoo et al. 2006]. An additional local treatment did not seem to give an advantage in terms of ORR, PFS and OS in comparison with systemic therapy alone, as stated by the literature [Signorelli et al. 2006]. Concerning the pts treated with anthracycline-containing CT with or without Rituximab (n=15), 8 pts (53%) and 5 pts (33%) achieved CR and PR respectively, 2 pts (13%) had a PD during treatment, only one pt in CR relapsed after 65 months from the first line therapy. After a median follow up of 27 months 12 pts (80%) are alive, 3 (20%) died in PD. The Response Rate and OS in the subgroup of pts that received anthracycline-containing CT resulted similar to those reported in the literature [Coiffier 2002]; therefore female genital involvement by NHL doesn’t seem to represent a negative prognostic factor.

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