Comparison of ICE (Ifosfamide-Carboplatin-Etoposide) Versus DHAP (Cytosine Arabinoside-Cisplatin-Dexamethasone) as Salvage Chemotherapy in Patients with Relapsed or Refractory Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4438-4438
Author(s):  
Yuksel Urun ◽  
Huseyin Abali ◽  
Berna Oksuzoglu ◽  
Burcin Budakoglu ◽  
Nuriye Yildirim ◽  
...  

Abstract Background: High dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) is currently the treatment of choice for relapsed or refractory lymphoma patients. However, the optimal salvage regimen for these patients is unclear. In this study, our aim was to compare the efficacy and toxicity profiles of DHAP and ICE regimens in the salvage treatment of relapsed and refractory lymphoma. Patients and methods: In this retrospective analysis, 53 patients with primary refractory or relapsed Hodgkin’s disease (HD) (n=13) or non-Hodgkin lymphoma (NHL) (n=40) who received ICE or DHAP salvage regimen were included. Results: Of 53 patients, 21 were female and the median age was 43 years. In the evaluable ICE group (n=22) rates of CR, PR, and ORR were 27%, 41% and 68% and in the DHAP group (n=27) rates of CR, PR, and ORR were 18%, 30% and 48% (p=0,24, for ORR). Of the 40 patients with NHL, 15 patients received ICE and 25 patients received DHAP. In the ICE group response could be evaluated in 12 patients, 3 (25%) achieved CR and 5 (42%) PR, leading to an ORR of 67%. In DHAP group, response could be evaluated in 24 patients, 5 (21%) achieved CR and 7 (29%) PR, which makes an ORR of 50%. Although response rate for ICE tends to be higher than DHAP, this difference was not statistically significant (p=0,48). Thirteen patients with HD had an ORR of 62%. One patient had a major response (CR + PR) in DHAP group (33%). In the ICE group of 10 patients with HD, ORR rate was 70%. The response rates for ICE for patients with NHL and HD were not statistically different (p=1,0). Toxicity with both regimens was within acceptable limits. The major grade III–IV toxicities for both groups were hematological (neutopenia and thrombocytopenia). The main non-hematological toxicity was renal and observed in 8 patients. Conclusion: Although the toxicity profiles of both ICE and DHAP regimens were similar in the treatment of patients with relapsed or refractory HD or NHL, ICE seems to be more effective in terms of response rates than DHAP regimen in whole cohort and subgroups but this difference was not statistically significant. Response of relapsed or refractory lymphoma patients to salvage chemotherapy regimens response ICE (n=22) n,% DHAP (n=27) n,% CR: complete response, PR: partial response, PBSC: peripheral blood stem cell CR 6 (27) 5 (18) PR 9 (41) 8 (30) CR+PR 15 (68) 13 (48) Failure 7 (32) 14 (52) Attempt to mobilize PBSC 8 (36) 2 (7) Successful mobilization 8 (36) 2 (7) Toxicity profiles of salvage chemotherapy regimens used for relapsed or refractory lymphoma patients ICE (n=25),n (%) DHAP (n=28), n (%) WHO: world health organization RBC: red blood cell, TX: transfusion PLT: platelet,G-CSF: granulocyte colony-stimulating factor No. of courses administered 1 3 (12) 7 (25) 2 5 (20) 4 (50) ≥3 17 (68) 7 (25) Total No. of courses administered 73 59 Toxicities (WHO grade III–IV) n=73 n=59 Neutropenia 13 (18) 8 (14) Thrombocytopenia 9 (12) 6 (10) Anemia 5 (7) 9 (15) Febrile neutopenia 6 (8) 6 (10) treated in patient 5 (7) 5 (8) Renal 4 (6) 4 (7) Total RBC TX (unit) 11 23 Total PLT TX (unit) 48 43 G-CSF 8 (11) 6 (10) TDDT 4 (6) 7 (12)

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2090-2090
Author(s):  
Jakub Svoboda ◽  
Rebecca Elstrom ◽  
Elise A. Chong ◽  
Charalambos Andreadis ◽  
Arnold Berkowitz ◽  
...  

Abstract High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard treatment for patients (pts) with relapsed or primary refractory lymphoma that is responding to salvage chemotherapy. Limitations of ASCT include significant morbidity, cost, restriction of further treatment options, and frequent relapse of lymphoma. To define the ability of FDG-PET to predict clinical outcome after ASCT, we conducted a retrospective analysis of lymphoma pts in our institution who received salvage chemotherapy followed by ASCT for relapsed or primary refractory lymphoma between 1999 and 2005. We identified 47 lymphoma pts (19 with diffuse large B-cell, 18 with Hodgkin, 4 with mantle cell, 3 with follicular and 3 with other lymphomas) who had an FDG-PET scan after at least two cycles of salvage chemotherapy and prior to ASCT. Three pts were excluded from the analysis because their FDG-PET scan results were non-conclusive. The remaining 44 pts (median age 44 yrs, range: 19–65) were categorized into FDG-PET scan negative (26 pts) and positive (18 pts) groups. Each group was evaluated for event-free survival (EFS), which was defined as the interval between the date of the transplant to the date of relapse after complete remission (CR) or the date of progression for pts without CR or the date of death from any cause without a documented relapse. The overall median follow-up was 14 mo (range: 2–58). There were no statistically significant differences in the distribution of lymphoma subtypes between the two groups. In the FDG-PET negative group, the median EFS was 18 mo (range: 3–58) with 14 pts (54%) remaining in CR. In the FDG-PET positive group, the median EFS was 5 mo (range: 1.5–19) with only 1 pt (6%) remaining in CR. Comparison between the two groups confirmed that the difference in the median EFS was highly statistically significant (p<0.001). Additional data to determine the correlation of the FDG-PET with conventional CT scans will be presented. Our study suggests that a positive FDG-PET scan after salvage chemotherapy and prior to ASCT indicates an extremely poor chance of achieving a prolonged remission after ASCT. Clinical trials of new approaches should be investigated for pts with relapsed or primary refractory lymphoma that remains detectable by FDG-PET after salvage chemotherapy. Figure Figure


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4433-4433
Author(s):  
Bastian von Tresckow ◽  
Annette Pluetschow ◽  
Heinz Haverkamp ◽  
Vladan Vucinic ◽  
Andreas Rank ◽  
...  

Abstract Introduction: The standard treatment for patients with relapsed or refractory (r/r) classical Hodgkin Lymphoma (cHL) is salvage chemotherapy followed by autologous stem cell transplantation (ASCT). The best outcome from the transplant is expected in patients who achieve complete remission (CR) after the salvage chemotherapy. Everolimus is a mammalian target of rapamycin (mTOR) inhibitor that has shown activity and an acceptable toxicity profile in patients with r/r cHL (Johnston PB et al. Am J Hematol 2010; Johnston PB et al. ISHL-9 2013). We therefore aim to improve the CR rate after salvage by an enforced salvage regimen consisting of everolimus plus time-intensified standard DHAP (Dexamethasone, High-Dose AraC [Cytarabine], Cisplatinum). Methods: We conducted a phase I trial of everolimus plus DHAP (ever-DHAP) for patients with r/r cHL eligible for ASCT to assess the recommended phase II dose (RPTD) of oral everolimus in this combination. Everolimus was administered for 14 days in each DHAP cycle starting from one day before DHAP. The second cycle of ever-DHAP was scheduled to start at day 14 of cycle one. Patients received two cycles of ever-DHAP. Everolimus dose levels of 2.5mg, 5mg, 7.5mg and 10mg were assessed in a modified 3+3 design. Generally, dose-limiting toxicity (DLT) was defined as CTCAE grade III/IV toxicity or unsuccessful stem cell mobilization. However, grade III/IV non-hematological toxicities known from DHAP were only counted as DLT from second occurrence in any patient onwards. Grade III/IV hematological toxicities were only counted as DLTs in case of prolonged time to recovery. Restaging by (PET)-CT was performed at day 21 of the second cycle given that the patient had recovered; PET was mandatory for all patients not achieving a CR in the CT scan. The rate of patients experiencing DLTs during 2 cycles of the combination therapy was the primary endpoint of the study. Secondary endpoints included adverse events, tumor related results of therapy or death, treatment administration, time to recovery after end of treatment and stem cell mobilization. Results: 14 patients were recruited between August 2012 and January 2014, all patients received at least one dose of everolimus. The median age was 33.5 years; six were female and eight were male. Eleven patients presented with stage III/IV disease. Overall, treatment was well tolerated. Two patients (both at the 7.5mg level) had a premature treatment termination and did not receive the 2nd cycle, one patient due to ototoxicity of grade I at investigator’s discretion and one patient due to neurotoxicity of grade III/IV. One additional patient (7.5mg cohort) suffered from ototoxicity of grade III/IV between end of treatment and restaging. Both grade III/IV toxicities were pre-defined as known from DHAP, thus they were not considered dose limiting at this first occurrence. No further non-hematological grade III/IV adverse events were reported. All patients but one experienced grade III/IV thrombocytopenia and leukopenia. No DLTs occurred and therefore 10mg of everolimus/day was chosen as RPTD. Duration of induction therapy including restaging after two cycles was 35-54 days. All patients who completed the 1st treatment cycle (n=13) had adequate stem cell mobilization (CD34+ cell count 2.9 - 31.1 x 106/kg; median 10 x 106/kg). So far one death occurred in a patient with pneumococcal sepsis one year after restaging. Responses according to CT scan in 12 patients who received two cycles of ever-DHAP were CR in 3 patients, CR unconfirmed (CRu) in 3 patients, partial remission (PR) in 5 patients and stable disease (SD) in 1 patient. This accounts for a CR/CRu rate of 50% (6/12) and an overall response rate of 92% (11/12). A PET scan was performed in 4 of 6 patients with CR/CRu; all had a negative PET (Deauville 1). In the 6 patients not achieving a CR/CRu 5 patients had a PET scan; 4 were PET positive (2 patients with Deauville 4 and 5 each) and 1 was PET negative (Deauville 1). Conclusions: Ever-DHAP with 10mg everolimus/day is safe and feasible in patients with r/r cHL. Based on the results of this phase I trial a randomized, placebo-controlled trial of ever-DHAP has been initiated and is currently recruiting. Disclosures von Tresckow: Takeda: Honoraria, Travel grants, Travel grants Other; Novartis: Honoraria, Research Funding. Off Label Use: Everolimus in relapsed or refractory Hodgkin Lymphoma. Topp:Affimed: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria. Engert:Millennium: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Affimed: Consultancy. Borchmann:Takeda: Honoraria, Research Funding, Travel grants Other.


2001 ◽  
Vol 19 (1) ◽  
pp. 81-88 ◽  
Author(s):  
O. Rick ◽  
C. Bokemeyer ◽  
J. Beyer ◽  
J. T. Hartmann ◽  
N. Schwella ◽  
...  

PURPOSE: To study feasibility and efficacy of a new salvage regimen in patients with relapsed and/or refractory germ cell tumors. PATIENTS AND METHODS: Between May 1995 and February 1997, 80 patients were entered onto a phase II study. Conventional-dose salvage treatment with three cycles of paclitaxel 175 mg/m2, ifosfamide 5 × 1.2 g/m2, and cisplatin 5 × 20 mg/m2 (TIP) was followed by one cycle of high-dose chemotherapy (HDCT) with carboplatin 500 mg/m2 × 3, etoposide 600 mg/m2 × 4, and thiotepa 150 to 250 mg/m2 × 3 (CET). In 23 patients, one additional cycle of paclitaxel 175 mg/m2 and ifosfamide 5 g/m2 (TI) was given immediately before TIP to improve stem-cell mobilization. RESULTS: Fifty-five (69%) of 80 patients responded to TIP, 24 (30%) of 80 patients had stable disease (n = 5) or tumor progression (n = 19), and one patient died. Only 62 (78%) of 80 patients received subsequent HDCT. Among those, 41 (66%) of 62 patients responded and 20 (32%) of 62 patients had stable disease (n = 3) or tumor progression (n = 17). One patient died after HDCT from multiorgan failure. Survival probabilities at 3 years were 30% for overall and 25% for event-free survival. Peripheral neurotoxicity with sensorimotor impairment grade 2 through 4 in 29%, paresthesias grade 2 through 4 in 24%, and skin toxicity grade 2 through 3 in 15% of patients were the most relevant side effects. CONCLUSION: Treatment with TIP followed by high-dose CET is feasible and can induce long-term remissions in 25% of patients with relapsed or refractory germ cell tumors. Peripheral nervous toxicity in approximately one third of patients is a disadvantage of this salvage strategy.


2007 ◽  
Vol 106 (5) ◽  
pp. 846-854 ◽  
Author(s):  
Carlos A. Mattozo ◽  
Antonio A. F. De Salles ◽  
Ivan A. Klement ◽  
Alessandra Gorgulho ◽  
David McArthur ◽  
...  

Object The authors analyzed the results of stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) for the treatment of recurrent meningiomas that were described at initial resection as showing aggressive, atypical, or malignant features (nonbenign). Methods Twenty-five patients who underwent SRS and/or SRT for nonbenign meningiomas between December 1992 and August 2004 were included. Thirteen of these patients underwent treatment for multiple primary or recurrent lesions. In all, 52 tumors were treated. All histological sections were reviewed and reclassified according to World Health Organization (WHO) 2000 guidelines as benign (Grade I), atypical (Grade II), or anaplastic (Grade III) meningiomas. The median follow-up period was 42 months. Seventeen (68%) of the cases were reclassified as follows: WHO Grade I (five cases), Grade II (11 cases), and Grade III (one case). Malignant progression occurred in eight cases (32%) during the follow-up period; these cases were considered as a separate group. The 3-year progression-free survival (PFS) rates for the Grades I, II, and III, and malignant progression groups were 100, 83, 0, and 11%, respectively (p < 0.001). In the Grade II group, the 3-year PFS rates for patients treated with SRS and SRT were 100 and 33%, respectively (p = 0.1). After initial treatment, 22 new tumors required treatment using SRS or SRT; 17 (77%) of them occurred inside the original resection cavity. Symptomatic edema developed in one patient (4%). Conclusions Stereotactic radiation treatment provided effective local control of “aggressive” Grade I and Grade II meningiomas, whereas Grade III lesions were associated with poor outcome. The outcome of cases in the malignant progression group was intermediate between that of the Grade II and Grade III groups, with the lesions showing a tendency toward malignancy.


2014 ◽  
Vol 05 (03) ◽  
pp. 244-249
Author(s):  
Abdul Rashid Bhat ◽  
Muhammed Afzal Wani ◽  
Altaf Rehman Kirmani ◽  
Altaf Umar Ramzan

ABSTRACT Context: Not enough literature is available to suggest a link between the histological subtypes of intracranial meningeal brain tumors, called ‘meningiomas’ and their location of origin. Aim: The evidence of correlation between the anatomical location of the intracranial meningiomas and the histopathological grades will facilitate specific diagnosis and accurate treatment. Materials and Methods: The retrospective study was conducted in a single high-patient-inflow Neurosurgical Center, under a standard and uniform medical protocol, over a period of 30 years from December 1982 to December 2012. The records of all the operated 729 meningiomas were analyzed from the patient files in the Medical Records Department. The biodata, x-rays, angiography, computed tomography (CT) scans, imaging, histopathological reports, and mortality were evaluated and results drawn. Results: The uncommon histopathological types of meningiomas (16.88%) had common locations of origin in the sphenoid ridge, posterior parafalcine, jugular foramen, peritorcular and intraventricular regions, cerebellopontine angle, and tentorial and petroclival areas. The histopathological World Health Organization (WHO) Grade I (Benign Type) meningiomas were noted in 89.30%, WHO Grade II (Atypical Type) in 5.90%, and WHO Grade III (Malignant Type) in 4.80% of all meningiomas. Meningiomas of 64.60% were found in females, 47.32% were in the age group of 41-50 years, and 3.43% meningiomas were found in children. An overall mortality of 6.04% was noted. WHO Grade III (malignant meningiomas) carried a high mortality (25.71%) and the most common sites of meningiomas with high mortality were: The cerebellopontine angles, intraventricular region, sphenoid ridge, tuberculum sellae, and the posterior parafalcine areas. Conclusion: The correlation between the histological subtypes and the anatomical location of intracranial meningeal brain tumors, called meningiomas, is evident, but further research is required to establish the link.


2020 ◽  
Vol 10 ◽  
Author(s):  
Weidong Tian ◽  
Jingdian Liu ◽  
Kai Zhao ◽  
Junwen Wang ◽  
Wei Jiang ◽  
...  

ObjectiveWHO grade III meningiomas are highly aggressive and lethal. However, there is a paucity of clinical information because of a low incidence rate, and little is known for prognostic factors. The aim of this work is to analyze clinical characteristics and prognosis in patients diagnosed as WHO grade III meningiomas.Methods36 patients with WHO grade III meningiomas were enrolled in this study. Data on gender, age, clinical presentation, preoperative Karnofsky Performance Status (KPS), histopathologic features, tumor size, location, radiologic findings, postoperative radiotherapy (RT), surgical treatment, and prognosis were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method. Univariate and multivariate analysis were conducted by the Cox regression model.ResultsMedian PFS is 20 months and median OS is 36 months in 36 patients with WHO grade III meningiomas. Patients with secondary tumors which transformed from low grade meningomas had lower PFS (p=0.0014) compared with primary group. Multivariate analysis revealed that tumors location (PFS, p=0.016; OS, p=0.013), Ki-67 index (PFS, p=0.004; OS, p&lt;0.001) and postoperative radiotherapy (PFS, p=0.006; OS, p&lt;0.001) were associated with prognosis.ConclusionWHO grade III meningiomas which progressed from low grade meningiomas were more prone to have recurrences or progression. Tumors location and Ki-67 index can be employed to predict patient outcomes. Adjuvant radiotherapy after surgery can significantly improve patient prognosis.


2018 ◽  
Vol 104 (6) ◽  
pp. 471-475 ◽  
Author(s):  
Mouhammed Kelta ◽  
Jamal Zekri ◽  
Ehab Abdelghany ◽  
Jalil Ur Rehman ◽  
Zahid Amin Khan ◽  
...  

Purpose: High-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) is used to treat patients with relapsed Hodgkin’s lymphoma. In this retrospective study we report our experience with patients who underwent HDCT and ASCT. Methods: All patients ≥15 years old with relapsed/refractory Hodgkin’s lymphoma who underwent HDCT and ASCT between June 2001 and December 2013 were included. Results: Fifty-four patients were identified. Median age at transplant was 22 years (range 15-49 years); 26 were men and 28 were women. Forty-eight patients (89%) underwent HDCT and ASCT after achieving a radiological response to salvage chemotherapy. The rate of radiological complete response to salvage chemotherapy was 13% and reached 50% within 3 months of ASCT in assessable patients. After a median follow-up of 25 months, 31 patients (57%) were still alive with no evidence of relapse or progression. Median event-free survival (EFS) was 24 months (95% CI 8.7-39.3) and 3-year EFS was 56%. Median overall survival (OS) was not reached and 3-year OS was 82.5%. Bulky mediastinal disease at relapse, hemoglobin level, and number of salvage regimens did not significantly impact EFS in univariate and multivariate analyses. After transplantation there was a trend towards longer EFS (30 vs. 24 months; p = 0.36) in patients with a longer time from the end of first-line treatment until relapse (≥12 vs. <12 months). The 100-day transplant-related mortality was 5.5%. Conclusions: HDCT and ASCT for relapsed/refractory Hodgkin’s lymphoma is safe. Our findings are consistent with published phase III results. Longer follow-up is warranted.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2075-2075 ◽  
Author(s):  
Karim Belhadj ◽  
Yosr Hicheri ◽  
Cécile Pautas ◽  
Taoufik El Gnaoui ◽  
François Hémery ◽  
...  

Abstract Follicular lymphomas have an indolent evolution with a median survival ranging between 8–10 years. At relapse, high-dose therapy followed by autologous stem-cell transplantation (ASCT) can be considered as an alternative to conventional chemotherapy. However, efficacy of this strategy remains controversial. The purpose of our retrospective study is to evaluate ASCT in the pre and post rituximab era as consolidation after 2nd or 3rd remission (at least PR). Between March 1989 and Apr 2004, 54 pts were treated at relapse with ASCT in our institution. At initial diagnosis, median age was 47 yrs (range 24–61) and FLIPI score was ≥ 3 in 18%. ASCT was performed in 2nd remission in 43 cases and in 3rd remission in 11 [median delay diagnosis-ASCT=44 months (range 7–139) and 53 months (range 21–227), respectively]. The conditioning regimens used were: VP16/cyclophosphamide/TBI in 33 cases, cyclophosphamide/TBI in 9, BEAM in 10 and cyclophosphamide/busulfan in 2. After ASCT, 49 pts achieved CR, 4 achieved PR and one pt progressed. In Dec 2004, with a median follow-up of 4.7 yrs, 27 pts (50%) had relapsed after ASCT with a median time to relapse of 12 months (range 2–95) and 18 pts have died. Causes of death were: lymphoma recurrence in 8 cases, secondary malignancy in 6 cases (3 MDS/AML, 2 radiation-associated solid tumors, 1 EBV associated lymphoma after a new salvage treatment including allogenic transplantation), and late infection in 4 cases, 2 of them occurring in remission (varicella and septicaemia) and 2 others after a new salvage therapy (cellulitis during chemotherapy-induced neutropenia and HHV6 encephalitis after allogenic transplantation). Ten-year overall survival (OS) from initial diagnosis was 68%. Five-year OS and event-free survival after ASCT were 74 and 52%, respectively. Patients treated at relapse before 1998 did not receive rituximab (rituximab-naive pts: n=29) and those treated after 1998 received a rituximab-based salvage regimen before ASCT (rituximab-treated pts: n=25). The main characteristics of the two populations were as indicated in the table below: rituximab-naive group rituximab-treated group N 29 25 FLIPI at initial diagnosis (Low/Intermediate/High) % 41/48/11 27/46/27 Median age at ASCT (yrs) 50 (range35–60) 52 (range 30–62) ASCT performed in 2nd remission 23 20 ASCT performed in 3rd remission 6 5 Median duration of response following last treatment line prior to ASCT (months) 21 (range 1–91) 11 (range1–49) After adjusting for the follow-up (median follow-up of the rituximab-treated group: 3.8 yrs), comparison between the two groups of pts treated with ASCT at relapse shows a significantly better OS of the rituximab-treated group as compared to that of the rituximab-naïve group (100 vs 61% at 4 years, p=0.01). These data suggest that the well-established efficacy of rituximab in FL is not abrogated by consolidative ASCT delivered at relapse in pts not previously treated with rituximab and further emphasize the superiority of immunochemotherapy over chemotherapy alone.


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