LACE - an Effective Conditioning Regimen for Lymphoma Patients Undergoing Autologous Transplant- Analysis of Outcomes and Prognostic Factors

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3979-3979
Author(s):  
Deepan Rajamanickam ◽  
Anant Gokarn ◽  
Alok Gupta ◽  
Sachin Punatar ◽  
Ravi Thippeswamy ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Prognostic Factors ◽  
Median Duration ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Salvage Chemotherapy ◽  
Pet Ct ◽  
First Relapse ◽  
Grade 3

Abstract Background: High dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the treatment of choice for patients with relapsed and refractory lymphomas. BEAM (BCNU, etoposide, cytarabine, melphalan) and CBV (cyclophosphamide, BCNU , VP-16) are most widely used conditioning regimens prior to ASCT in lymphomas. LACE has been found to be an effective regimen though outcome data is sparse.As BCNU was difficult to procure in India, we began using this regimen since November 2007. This study is a retrospective analysis to evaluate outcomes and possible prognostic factors in this cohort of patients. Methods: All patients between November 2007- January 2014 who received LACE regimen for primary progressive, chemotherapy sensitive relapse or relapsed-refractory Hodgkin’s (HL) and non- Hodgkin’s lymphoma (NHL) were included.Patients received salvage chemotherapy with either GDP, ICE, MINE or DHAP with or without rituximab (NHL patients). PET-CT was performed in all patients after 2-3 cycles of salvage chemotherapy. Response assessment was performed according to Cheson’s criteria. Patients underwent peripheral blood stem cell collection after 3rd or 4th cycle of salvage chemotherapy.Conditioning regimen used was LACE (lomustine-200 mg/m2 d-7, etoposide 1000mg/m2 d-7, ara-c 2000 mg/m2 d-6, d-5 and cyclophosphamide 1800 mg/m2 d-4 to d-2). PET-CT was done on day 100, 1 year post transplant and then yearly for next 4 years. Incidence and grade of treatment related toxicity was recorded according to CTCAE V-3. Prognostic factors evaluated for overall survival (OS) and progression-free survival (PFS) included time between diagnosis – transplant; time between CR1 - first relapse; baseline, presalvage and pretransplant serum albumin,LDH and B2 microglobulin; PET positivity pretransplant, at day 100 and day 360; remission status at time of transplant; IPI (NHL) and IPS (HL) at baseline and at relapse; stage at diagnosis and at relapse. Probabilities of OS and PFS were estimated using the Kaplan–Meier method. Univariate comparisons of survival times for potential prognostic factors were made using the log-rank test. Multivariate analysis of significant factors was performed by Cox –regression analysis. Results: Seventy patients had HL while 30 NHL (Male-73, Female-27) with median age at transplant of 23 years. In NHL cohort, 19 were DLBCL, 6 were T-cell lymphomas, 4 mantle cell lymphoma and 1 Burkitt’s lymphoma.The median time from complete remission (CR) to first relapse and time from diagnosis to transplant were 1.4 and 1.9 years respectively. The median number of lines of chemotherapy pre transplant was 2. GDP (53 patients) was the most commonly used salvage chemotherapy. At the time of transplant, 68% were in CR, 29% in partial remission (PR) and 3% had refractory state. The incidence of grade 3-4 oral mucositis was 8% with a median duration of 3.5 days. The incidence of grade 3-4 diarrhea was 4% with median duration of 3 days. Median days to myeloid and platelet engraftment were 10 and 13 respectively. The median follow-up was 2.9 years. The probability of OS and PFS at 5 years was 67% and 57% for the whole group, 73% and 62% in HL group and 51% and 46% in NHL group. Seven patients died due to transplant related causes which included 6 due to sepsis and 1 due to herpes simplex encephalitis. In univariate analysis for OS, PET negativity pre transplant (P= 0.03), at day 100 (P= 0.019) and at day 360 (P= 0.01) were associated with better OS. Similarly, HL patients with IPS 0-2 (P=0.002) at time of relapse had better OS. Univariate analysis for PFS showed that PET negativity pre transplant (P=0.002), at day 100 (P= 0.0001) and at day 360 (P=0.00) was associated with better PFS. HL patients with IPS 0-2 (P=0.000) and NHL patients with IPI 0-2 at time of relapse (P=0.007) had better PFS. Patients in CR at the time of transplant had better PFS than those in not in CR (P=0.008). Overall HL patients had better OS (P=0.037) and PFS (P=0.097) compared to NHL group. Multivariate analysis for OS (P= 0.021) and PFS (P=0.001) revealed PET negativity at day 100 as the only significant prognostic factor. Conclusions: This is the largest reported cohort of lymphoma patients transplanted with LACE regimen. LACE is effective and well tolerated conditioning regimen in lymphoma transplant. PET negativity at various time points pre and post transplant prognosticates for better survival. Disclosures No relevant conflicts of interest to declare.

scholarly journals Prognostic Significance of Metabolic Parameters by 18F-FDG PET/CT in Thymic Epithelial Tumors

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 712
Author(s):  
Joohee Lee ◽  
Young Seok Cho ◽  
Jhingook Kim ◽  
Young Mog Shim ◽  
Kyung-Han Lee ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Fdg Pet ◽  
Univariate Analysis ◽  
Thymic Epithelial Tumors ◽  
Epithelial Tumors ◽  
Masaoka Stage ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct

Background: Imaging tumor FDG avidity could complement prognostic implication in thymic epithelial tumors. We thus investigated the prognostic value of volume-based 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT parameters in thymic epithelial tumors with other clinical prognostic factors. Methods: This is a retrospective study that included 83 patients who were diagnosed with thymic epithelial tumors and underwent pretreatment 18F-FDG PET/CT. PET parameters, including maximum and average standardized uptake values (SUVmax, SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), were measured with a threshold of SUV 2.5. Univariate and multivariate analysis of PET parameters and clinicopathologic variables for time-to-progression was performed by using a Cox proportional hazard regression model. Results: There were 21 low-risk thymomas (25.3%), 27 high-risk thymomas (32.5%), and 35 thymic carcinomas (42.2%). Recurrence or disease progression occurred in 24 patients (28.9%). On univariate analysis, Masaoka stage (p < 0.001); histologic types (p = 0.009); treatment modality (p = 0.001); and SUVmax, SUVavg, MTV, and TLG (all p < 0.001) were significant prognostic factors. SUVavg (p < 0.001) and Masaoka stage (p = 0.001) were independent prognostic factors on multivariate analysis. Conclusion: SUVavg and Masaoka stage are independent prognostic factors in thymic epithelial tumors.

Do pathological parameters of primary tumor correlate with overall survival (OS) of metastatic clear-cell renal cell carcinoma (ccRCC)?

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 549-549
Author(s):  
Umberto Basso ◽  
Marco Maruzzo ◽  
Anna Paola Fraccon ◽  
Teodoro Sava ◽  
Francesco Massari ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Primary Tumor ◽  
Clinical Laboratory ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Fuhrman Grade ◽  
Metastatic Setting ◽  
N Stage ◽  
Grade 3

549 Background: T and N stage, Fuhrman grade, necrosis and sarcomatoid features in the primary tumor are key prognostic factors for relapse of ccRCC, but they are not part of Heng's algorithm applied to predict OS in the metastatic setting, which instead is based on 6 clinical/laboratory items. Methods: Retrospective analysis on correlation between pathological parameters and OS (from start of first-line targeted therapy) and Heng's prognostic factors in a multicenter cohort of pts with advanced ccRCC, all of whom had undergone surgery on the kidney. Results: From 2006 to 2012, data of 903 eligible metastatic pts were collected from 33 Italian Oncology Institutions, median age 66 years, 72.6% males, 36.4 metastatic at diagnosis. After a median observation of 42 mo, 70,5% of pts died, estimated OS is 28.5 mo. Heng good prognosis pts were 14.45%, intermediate 69.1% and poor 16.45%. Univariate analysis showed that all pathological parameters significantly correlated with OS: T stage 3-4 vs 1-2 (HR 1.3), N1 vs N0 (1.3), Fuhrman grade 3-4 vs 1-2 (1.7) presence of necrosis (1.5) and sarcomatoid features (1,6). All pathological parameters had a strong correlation with a time to metastases < 1 year, while only weak correlations were found with the other clinical prognostic items of Heng's model. At multivariate analysis only N stage showed an independent impact on OS (table). Conclusions: T3-4 stage, N1, Fuhrman grade 3-4, presence of necrosis and sarcomatoid features negatively affect OS of metastatic ccRCC, but clinical items of Heng's model confirm to have a more robust prognostic significance at multivariate analysis. [Table: see text]

Antithymocyte Globulins (ATG) as Part of the Myeloablative Conditioning (MAC) Regimen Can Reduce the Risk of Severe Graft-Vs.-Host Disease (GVHD) after Allogeneic Stem Cell Transplantation (allo-SCT) from Matched-Unrelated Donors (MUD).

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1151-1151
Author(s):  
Mohamad Mohty ◽  
Marie- Lorraine Balere ◽  
Gerard Socie ◽  
Noel-Jean Milpied ◽  
Norbert Ifrah ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Beneficial Effect ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Hla Typing ◽  
High Dose ◽  
Increased Risk ◽  
Grade 3

Abstract The use of ATG in the setting of standard MAC allo-SCT is still controversial. Some studies, however, suggested a beneficial effect of ATG in preventing acute GVHD. Here, we report the results of a large multicenter retrospective study analyzing the effect of ATG, incorporated within the MAC regimen for MUD-transplants in leukemic patients compared to patients not receiving ATG. The purpose of the study was to compare the incidence and severity of acute and chronic GVHD as well as non-relapse mortality (NRM), leukemiafree and overall survivals (LFS, OS). The study included 171 adult patients with acute leukemia and MDS (73% standard risk and 27% more advanced disease) reported to the registry of the SFGM-TC between 1998 and 2004, and for whom detailed allelic HLA typing (4 digits) for the recipient and the donor was available. Patients’ characteristics were as follow: median age: 33 (range, 15–67), 57% male recipients, 35% female donors, 44% AML, 43% ALL, 11% MDS and 2% unclassified leukemia. The stem cell source was bone marrow in 72.5% of patients, while PBSCs were used in 27.5% of cases. 81% of patients were transplanted from 10/10 allelic MUD, and 19% from a MUD with at least one allelic difference. A high dose TBI-based MAC regimen was used in 84% of cases, while 16% received a high-dose chemotherapy containing MAC regimen. 85% of the patients received the classical CsA and short course methotrexate GVHD prophylaxis regimen. In this series, 120 patients (70%) did not receive ATG (“no-ATG” group), while 51 patients received ATG (“ATG” group; Thymoglobuline*-Genzyme in all cases; total ATG dose: ≤5 mg/Kg, n=13; &gt;5 and &lt;10 mg/Kg, n=17; ≥10 mg/Kg, n=21) as part of the MAC regimen. Except for a significantly higher number of allelic differences between recipient and donor (33% vs. 13%; P=0.002), the “no-ATG” and “ATG” groups were strictly comparable as for patients, disease and transplant characteristics. 95% of patients had a sustained engraftment at a median of 20 (range, 9–41) days after allo-SCT with no significant differences between the 2 groups. With a median followup of 30.3 (range, 2.6–68.1) months after allo-SCT, grade 0–1 and 2–4 acute GVHD occurred in 74 (46%) and 88 patients (54%) respectively, with grade 3–4 acute GVHD being significantly lower in the “ATG” group as compared to the “no-ATG” group (18% vs. 32%; P=0.04). In this series, 142 patients (83%) were evaluable for chronic GVHD. Limited and extensive chronic GVHD were observed in 22 and 25% of assessable patients respectively, with extensive chronic GVHD being significantly lower in the “ATG” group as compared to the “no-ATG” group (5% vs. 33%; P=0.001). Interestingly, patients from the “ATG” group had a higher incidence of limited chronic GVHD (33% vs. 18%; P=0.06). The use of ATG was not associated with a higher risk of infections: infection-related mortality was comparable between both groups (23% vs. 27%, P=NS). Also, NRM was comparable between both groups (30% vs. 29%; P=NS). In multivariate analysis including all relevant risk factors tested in the univariate analysis, we found that an HLA allelic mismatch and the non-use of ATG were associated with an increased risk of severe grade 3–4 acute GVHD (RR=2.80, 95%CI, 1.5–5.3), P=0.001; and RR=2.4, 95%CI, 1.1–5.0, P=0.02 respectively). Similarly, multivariate analysis showed that the absence of use of ATG was the unique and strongest parameter associated with an increased risk of extensive chronic GVHD (RR=6.9; 95%CI, 1.7–29.0, P=0.008). Finally, LFS and OS at 2 years were not significantly different between the “no-ATG” and “ATG” group (48.8% vs. 41.3%, P=NS; and 53.6% vs. 54.3%, P=NS; respectively) Despite its retrospective nature, these results strongly indicate a global long-term beneficial effect of ATG when used as part of the MAC regimen prior to allo-SCT from MUD (especially in the HLA mismatch setting). Though prospective studies are needed to assess the optimal ATG dosing and administration schedule, such protective effect of ATG against severe acute and chronic GVHD, can be likely achieved without an increased risk of infections or leukemia recurrence.

Allogeneic Stem Cell Transplantation (alloSCT) and Donor Lymphocyte Infusion (DLI) In Patients with Non-Hodgkin Lymphoma (NHL) Who Experienced Relapse or Progression After Autologous Stem Cell Transplantation (autoSCT): Retrospective Analysis From the Korean Society of Blood and Marrow Transplantation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3536-3536 ◽  
Author(s):  
Ji-Won Kim ◽  
Byung-Su Kim ◽  
Soo-Mee Bang ◽  
Inho Kim ◽  
Dong Hwan Kim ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Serum Albumin ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
Stage Iv ◽  
Grade 3 ◽  
Ecog Ps ◽  
Significant Factors

Abstract Abstract 3536 Prognosis of patients with NHL who underwent relapse or progression after autoSCT is generally dismal and treatment option is limited. AlloSCT has been performed to overcome this problem and long term survivors have been reported. However, substantial transplant-related mortality (TRM) is a significant problem. We report clinical outcomes of alloSCT in these patients and DLI after failure of alloSCT along with analysis of risk factors for treatment results and adverse events. This retrospective study was performed in 7 hospitals in Korea. Candidate risk factors were age, sex, histology, Ann Arbor stage at diagnosis, number of prior treatments, time to progression (TTP) after autoSCT, bone marrow involvement, Eastern Cooperative Oncology Group (ECOG) performance status (PS), donor type, stem cell source, conditioning regimens of alloSCT, serum lactate dehydrogenase (above 250 IU/L), serum albumin (above 3.0 g/dL), and acute graft-versus-host disease (aGvHD). Between August 1998 and March 2009, 38 patients received alloSCT. Median age was 37 (range, 17–54) years. Male to female ratio was 26:12. Eighteen patients (47.4%) had B-cell lymphoma and 20 patients (52.6%), T/NK-cell lymphoma. Before alloSCT, patients had received median 4 (range, 2–7) prior treatments including autoSCT. Median TTP after autoSCT was 5.9 (range, 0.8–35.8) months. Twenty four patients (63.2%) received stem cells from related donors and 14 patients (36.8%) from unrelated donors. Median number of CD34+ cells infused was 5.41 × 106 (range, 0.86 × 106-16.60 × 106) /kg. Eighteen patients (47.4%) underwent a myeloablative conditioning and 20 patients (52.6%), a reduced intensity conditioning. During a median follow-up of 45.2 (range, 1.3–137.1) months, 24 patients (63.2%) experienced treatment failure and 22 patients (57.9%) died. Median event-free survival (EFS) was 6.3 (95% confidence interval (CI), 4.3–8.4) months. Median overall survival (OS) was 19.0 (95% CI, 3.8–34.2) months. Estimated 5-year survival rate was 35.0% (Figure). Treatment response was evaluable in 30 patients. Response rate was 73.3%; complete remission (CR) was achieved in 20 patients (66.7%) and partial response in 2 patients (6.7%). Grade 3 or 4 renal toxicity developed in 6 patients (15.8%), grade 3 or 4 hepatic toxicity in 15 patients (39.5%) including veno-occlusive disease (VOD) in 6 patients (15.8%), aGvHD in 13 patients (34.2%), and neutropenic fever in 34 patients (89.5%) including documented sepsis in 11 patients (28.9%). TRM was reported in 8 patients (21.1%). Causes of TRM were infection in 7 patients and VOD in 1 patient. In univariate analysis, no significant association was found with treatment response. By contrast, EFS was related to stage (p=0.039), TTP after autoSCT (p=0.033), and PS (p<0.001). OS was associated with stage (p=0.037), number of prior treatments (p=0.049), TTP after autoSCT (p=0.032), PS (p<0.001), and serum albumin (p=0.016). On the other hand, aGvHD was not associated with EFS (p=0.545) and OS (p=0.476). Multivariate analysis demonstrated that stage IV (hazard ratio (HR) 2.85 (95% CI, 1.13–7.22); p=0.027) and ECOG PS 2 (HR 3.94 (95% CI, 2.08–7.47); p<0.001) were significant factors for EFS and that stage IV (HR 3.28 (95% CI, 1.19–9.04); p=0.022), ECOG PS 2 (HR 5.26 (95% CI, 2.22–12.48); p<0.001), and serum albumin above 3.0 g/dL (HR 0.15 (95% CI, 0.03–0.63); p=0.010) were significant factors for OS. TRM was associated with PS (p=0.010) and serum albumin (p=0.040) by univariate analysis. Multivariate analysis showed that ECOG PS 2 was the only significant factor for TRM (relative risk (RR) 11.77 (95% CI, 1.43–97.01); p=0.022). ECOG PS 2 was also a significant factor for documented sepsis (RR 7.14 (95% CI, 1.08–47.42); p=0.042). DLI was performed in 8 patients who failed alloSCT. After median 1.5 (range, 1–6) cycles of DLI, 2 patients achieved CR. Grade III or IV aGvHD developed in these patients. By contrast, among 6 patients who failed to achieve CR, aGvHD developed in 2 patients. In conclusion, alloSCT is a viable option for patients with NHL who failed autoSCT despite high TRM. Stage and PS were significant factors for EFS and OS. Serum albumin was a significant factor for OS. In patients with ECOG PS 2, alloSCT should be avoided and novel treatment approaches should be offered due to high risk of TRM. DLI after failure of alloSCT showed promising results, which supports the presence of graft-versus-lymphoma effect. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Stem Cell Transplantation - A Long-Term Curative Approach In Patients ≥ 60 Years With Advanced Disease AML/MDS, - The Freiburg Experience Of 250 Consecutive Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2135-2135
Author(s):  
Hartmut Bertz ◽  
Michael Lübbert ◽  
Kristin Ohneberg ◽  
Ralph Wäsch ◽  
Robert Zeiser ◽  
...  
Keyword(s):  
Stem Cell ◽  
Prognostic Factors ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Advanced Disease ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Hematopoietic Stem

Abstract Since the introduction of reduced-toxicity conditioning prior to allogeneic hematopoietic stem cell transplantation (alloSCT) we transplanted from 1999 to 2012, 250 consecutive patients (pts) with myeloid malignancies (AML, MDS) aged ≥ 60 years (yrs). The 144 male and 106 female pts with a median age of 66 yrs (range 60-77) were transplanted for de novo AML (n=95), s/tAML (n=104) and MDS (n=51) with 89% unfavorable cytogenetics (CALGB). Since 2004 pts received a prospective fitness assessment (Deschler et al., Haematologica 2013). In 74% the donor was matched/mismatched unrelated and in 26% related. Only 16% were transplanted in CR1/2, 84 % with advanced or untreated disease. The conditioning regimen was the FBM protocol (fludarabine, carmustine, melphalan; Bertz et al., JCO 2003) in 98%, and 97% of the pts received PBSC. For GVHD prophylaxis in 91% a combination of cyclosporine plus alemtuzumab or ATG-F™ was used. At day +30, 94% of the pts had achieved CR by standard measures. With a median follow up of 57 months (3-157) 37% of the pts are alive; main causes of death were relapse (n=62), infection (n=35) and age-related diseases (n=13). The probability of OS/DFS was at 1yr 61%/49%, at 2 yrs 49%/41% and at 5 yrs 37%/34%, respectively. The probability for NRM at 1 yr is 24%. Nineteen known prognostic factors for outcome were evaluated: e.g. patient and donor age, graft size, days between diagnosis and alloHCT, CMV, early/advanced disease, cytogenetics, Sorror and Gratwohl score, donor type, HLA-identity. In the multivariate analysis a better OS (factors with p<0.1; table) was seen with a matched donor; a better DFS with a related donor, and high CD34+ graft content; in contrast, a mismatched donor is a risk factor for reduced DFS.TableMultivariate analysis of prognostic factors* for OS and DFSvariablevalueHazard Ratio95% CI lower limit95% CI upper limitP valueOverall survivalRemission at alloHCTadvanced1.370.862.160.1825HLA mismatchyes1.401.011.960.0463HCT-CI (Sorror)>= 21.311.011.960.1007Peripheral blood blastsyes1.210.841.760.3034Disease-free survivalRemission at alloHCTadvanced1.290.722.300.3946Donorrelated0.640.430.950.0258HLA mismatchyes1.440.992.090.0561CD34+ cells> median0.760.551.040.0867Bone marrow blasts> 5%1.210.781.880.3915*in univariate analysis p<0.157 (AIC criterion; Sauerbrei W, 1999 Applied Statistics,48:313-329.70.) In conclusion, this unique large cohort of older pts with AML/MDS with mainly advanced disease and unfavorable cytogenetics shows a high feasibility, safety and efficacy of alloHCT after the FBM protocol. AML/MDS pts in their 7th and 8th decade of life fit for transplant should be evaluated for alloHCT as very important long-term curative option. Disclosures: No relevant conflicts of interest to declare.

A Phase II Study Of V-BEAM (Bortezomib, Carmustine, Etoposide, Cytarabine, and Melphalan) As Conditioning Regimen Prior To Second Autologous Stem Cell Transplantation For Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5492-5492 ◽  
Author(s):  
Tzu-Fei Wang ◽  
Mark A. Fiala ◽  
Ningying Wu ◽  
Theresa Fletcher ◽  
Camille N. Abboud ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Clostridium Difficile ◽  
Median Duration ◽  
Research Funding ◽  
Conditioning Regimen ◽  
Response Rates ◽  
Grade 3 ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Background High-dose melphalan (HDM) has been the standard conditioning regimen for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) for decades. Second ASCT is often offered as salvage therapy for patients who relapse after a first ASCT, but while response rates are similar, the progression free survival (PFS) is rarely comparable with that of the first ASCT when HDM conditioning is used for both. BEAM (carmustine, etoposide, cytarabine, and melphalan) is one of the most commonly used conditioning regimens for lymphoma patients undergoing ASCT and all of the components have been shown to be effective in refractory MM, but it has not been tested as a conditioning regimen for ASCT in MM. Bortezomib has been incorporated with HDM as a conditioning regimen for initial ASCT, with promising outcomes and limited toxicities. Based on these findings, we proposed a new conditioning regimen, V-BEAM (bortezomib-BEAM), administered prior to a second ASCT for relapsed/progressive MM, aiming to improve the response rates and PFS of the second ASCT. Objectives To evaluate the safety and efficacy of a new conditioning regimen, V-BEAM, prior to a second ASCT in patients with relapsed/progressive MM after a first ASCT with HDM conditioning. Patient/Methods Patients with relapsed/progressive MM after a previous ASCT with HDM conditioning were enrolled after 2 to 6 cycles of induction chemotherapy with a bortezomib or carfilzomib based regimen. Patients who had progressive disease on induction chemotherapy were excluded. V-BEAM was administered as the following: Bortezomib 1.3 mg/m2 on days -6, -3, +1, and +4, carmustine 300 mg/m2 on day -7, etoposide 100 mg/m2 and cytarabine 100 mg/m2 each twice daily on days -6 through -3, and melphalan 140 mg/m2 on day -2. On day 0, autologous stem cells (> 2.0x106/kg) were infused. No maintenance or consolidation therapy was given post-transplant. Results A total of 10 patients were enrolled from October 2012 to May 2013 at the Siteman Cancer Center. The median age was 64.5 years old (range, 48-68) and 50% were male. Seventy percent of patients were Durie-Salmon stage IIIA at diagnosis, while the remaining 30% were stage IIA. The median time to progression following previous autologous stem cell transplant was 29 months (range, 17-97). The median number of prior therapies (including first ASCT) was 4 (range, 3-6). At the time of abstract submission, one patient has not reached day +100 and two patients expired within 30 days of transplant. For the remaining seven patients, the day +100 response rates include five complete responses (CR) and two very good partial responses (VGPR). To date, no patients have had subsequent disease progression after a median follow-up of 5.0 months (range, 2.3-9.3). Two patients suffered from treatment related mortality (one from neutropenic colitis [Day +18] and the other from sepsis [Day +2]). Serious complications included: neutropenic fevers (100%), diarrhea (grade 3-4, 100%), oral mucositis (all grade, 100%; grade 3-4, 20%), sepsis (30%), Clostridium difficile colitis (30%), and neutropenic colitis without Clostridium difficile (30%). Two patients (20%) had new or worsening peripheral neuropathy, both of which were grade 2 and easily controlled. The median duration of hospitalization was 23 days (range, 19-29). The median duration of neutrophil engraftment and platelet engraftment (>20x109/L) were 10 days (range, 9-11) and 22.5 days (range, 17-36), respectively. The median duration of intravenous antibiotics was 14 days (range, 2-23). Two patients were readmitted shortly following discharge for neutropenic fevers and candida esophagitis, respectively. In June 2013, eight months after study initiation, the decision was made to terminate the study due to excessive toxicity. Conclusion While the new conditioning regimen V-BEAM prior to a second ASCT produced promising response rates for relapsed/progressive MM, it resulted in unexpected treatment related mortality and should not be investigated further without modifications. Disclosures: Off Label Use: BEAM regimen as a conditioning regimen for relapsed multiple myeloma. Abboud:Ariad, Alexion, Novartis, Teva: Honoraria, Speakers Bureau. Stockerl-Goldstein:Millennium: Speakers Bureau; Celgene : Speakers Bureau. Vij:Celgene : Honoraria, Research Funding, Speakers Bureau; Millennium: Honoraria, Speakers Bureau; Onyx: Honoraria, Research Funding, Speakers Bureau.

Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation for Adult Patients with T-Cell Acute Lymphoblastic Leukemia: A Survey From the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 356-356
Author(s):  
Xavier Cahu ◽  
Myriam Labopin ◽  
Sebastian Giebel ◽  
Gerard Socie ◽  
Dietrich Beelen ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Donor Type ◽  
Cell Acute Lymphoblastic Leukemia

Abstract Abstract 356 Background: T-cell acute lymphoblastic leukemia (T-ALL) comprises about 25% of all adult ALL. Although allogeneic hematopoietic stem cell transplantation (allo-SCT) exerts a graft versus leukemia effect, very few large series exist on the outcome of adult T-ALL patients allografted with a myeloablative conditioning regimen. Patients and methods: adult cases of T-ALL patients who underwent related or unrelated (6/6) allo-SCT with a myeloablative regimen between 2000 and 2010 were extracted from the EBMT registry. Patients with a prior autologous or allogeneic SCT and those who received cord blood allo-SCT were excluded from analysis. Primary goal of the study was to evaluate overall survival (OS), leukemia-free survival (LFS), non-relapse mortality (NRM) and relapse incidence (RI) for T-ALL patients in first (CR1), second or subsequent remission (CR2+) and in relapse or refractory disease (advanced). Results: 886 patients were included in this study. The median follow-up was 43 months. The median age was 29 (range: 18–63) and 649 patients (73%) were males. Allo-SCT characteristics are described in table 1. Among patients (n=561) allografted in CR1, 25% had a white blood cell count (WBC) ≥100 G/L, and a complex karyotype was identified in 43 cases (16%, available data = 268). 4-year OS and 4-year LFS were 58% (standard deviation (SD) 2%) and 55% (SD 2%), respectively, whereas 4-year NRM and RI were 19% (SD 2%) and 26% (SD 2%), respectively. In univariate analysis, age < median age (60% versus 50%, p = 0.02) and use of total-body-irradiation (TBI) (57% versus 42%, p = 0.04) were associated with an improved 4-year LFS. In a multivariate analysis including age, use of TBI, donor type and donor sex, age <median age (Hazard Ratio (HR)= 0.71 [95% CI: 0.55–0.92], p=0.01) and use of TBI (HR = 0.67 [0.48–0.93], p=0.02) were associated with an improved LFS. In the CR2+ T-ALL group (n=151), 4-year OS and 4-year LFS were 25% (SD 4%) and 24% (SD 4%), respectively. 4-year NRM was 27% (SD 4%) whereas 4-year RI was 49% (SD 4%). In univariate analysis, use of TBI was associated with an improved 4-year LFS (29% versus 8%, p = 0.02). In a multivariate analysis including age, patient sex, use of TBI and donor type, use of TBI was associated with an improved LFS (HR = 0.57 [0.37–0.88], p=0.01). Finally, in the advanced T-ALL group (n=174), 4-year OS and 4-year LFS were 15% (SD 3%) and 12% (SD 3%), respectively. 4-year NRM was 30% (SD 4%), whereas 4-year RI was 58% (SD 4%). In univariate analysis, use of TBI was associated with an improved 4-year LFS (16% versus 3%, p= 0.002). In a multivariate analysis including age, use of TBI and donor type, use of TBI was again associated with an improved LFS (HR=0.56 [0.38–0.82], p=0.003). Conclusion: This large series demonstrates that myeloablative conditioning allo-SCT is followed by a relatively favorable outcome in patients with T-ALL transplanted in CR1, and might be an option for subgroups of patients in more advanced phase of the disease. Of note, use of TBI as part of the conditioning regimen is associated with an improved LFS in all disease stages. Disclosures: No relevant conflicts of interest to declare.

Prognostic factors for severe diarrhea in patients with locally advanced rectal carcinoma treated with neoadjuvant chemoradiation with capecitabine: A single-center cohort study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15176-e15176
Author(s):  
Wesley Hartman ◽  
Esther Oomen De Hoop ◽  
Cornelis Verhoef ◽  
Joost Nuyttens ◽  
Esther van Meerten
Keyword(s):  
Multivariate Analysis ◽  
Cohort Study ◽  
Prognostic Factors ◽  
Rectal Carcinoma ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Female Gender ◽  
Neoadjuvant Chemoradiation ◽  
Tertiary Center ◽  
Grade 3

e15176 Background: Chemoradiation with concomitant capecitabine (CRT) followed by total mesorectal excision is the standard of care for locally advanced rectal carcinoma (LARC). Grade ≥ 3 diarrhea is considered a dose-limiting toxicity of adding capecitabine to radiotherapy. The aim of this study is to describe the risk factors of grade ≥ 3 diarrhea in patients with LARC during CRT. Methods: A single centre retrospective cohort study was conducted in our tertiary center. All patients with LARC treated with CRT from 2009 to 2015 were included. Patients with local recurrence who received CRT for the first time were also included. Univariate logistic regression analyses were used, followed by a multivariate analysis of the significant factors with backward selection at p < 0.05. Results: A total of 738 patients were included: 67% male, median age 64 years (range 17-88), 95% primary presentation. DPYD-testing was not performed upfront. In this cohort 69 patients (9%) developed ≥3 grade diarrhea. In the univariate analysis, factors significantly associated with ≥3 grade diarrhea were; female gender, age ≥65 years, body weight and decreased renal function (defined as MDRD GFR < 60 ml/min/1,73 m2). The following factors remained significantly associated with ≥3 grade diarrhea in the multivariate analysis; female gender (odds ratio (OR) 2.77, 95% confidence interval (CI) 1.54-4.99, p 0.001), age ≥65 years (OR 2.85, 95% CI 1.63-4.98, p < 0.001) and a lower bodyweight (OR 0.98, 95% CI 0.96-1.00, p 0.015). Conclusions: Female gender and age ≥65 years significantly increase the risk of grade ≥ 3 diarrhea caused by neoadjuvant CRT for LARC. So, older female patient must be closely watched during this treatment to intervene on time. The difference in toxicity between females and males might be explained by the pelvic anatomical differences between men and women. The found prognostic factors will be validated in a second cohort of patients with LARC treated with CRT. Besides, sarcopenia will be tested as a prognostic factor as well.

scholarly journals Obinutuzumab Plus Gemcitabine, Dexamethasone and Cisplatin (O-GDP) As Salvage Chemotherapy Prior to Autologous Stem Cell Transplant in Aggressive B Cell Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4610-4610
Author(s):  
Michael D. Jain ◽  
Ryan D. Morin ◽  
Anca Prica ◽  
Vishal Kukreti ◽  
Robert Kridel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Research Funding ◽  
Metabolic Response ◽  
B Cell Lymphoma ◽  
Autologous Stem Cell Transplant ◽  
Salvage Chemotherapy ◽  
Ct Imaging ◽  
Cell Transplant ◽  
Pet Ct ◽  
Grade 3

Abstract Background: The LY.12 randomized phase 3 clinical trial defined gemcitabine, dexamethasone and cisplatin (GDP) as an effective outpatient salvage chemotherapy regimen in relapsed/refractory (R/R) patients with aggressive lymphomas who are candidates for autologous stem cell transplant (ASCT) (Crump et al. JCO 2014). When the anti-CD20 antibody rituximab (R) was added to GDP, the ORR was 45.6% by CT imaging and 51.9% of patients were able to receive ASCT. Obinutuzumab (O) is a type 2 CD20 antibody that has demonstrated superiority to R in some studies in indolent lymphomas and is active in R-refractory follicular lymphoma. Improvements in the outcome of salvage therapy have tested alternative CD20 antibodies (Van Imhoff, JCO 2017), to date without success. We report a single centre, single arm clinical trial of O-GDP to assess safety and efficacy in R/R aggressive B cell lymphoma. Methods: Transplant eligible patients with DLBCL and transformed indolent lymphoma were treated with O-GDP for two cycles, followed by response assessment by CT. Non-progressors received a third cycle of O-GDP for stem cell mobilization and a PET/CT scan was obtained after stem cell collection. Responders then proceeded to ASCT per investigator decision. O was given at 1000 mg weekly during the first cycle of GDP and then on day 1 of cycles 2 and 3. Responses were determined by Lugano criteria using investigator assessment. The primary outcome was ORR by CT imaging after 2 cycles. The pre-specified statistical analysis stated that the trial will be declared positive if the ORR was >60%, negative if the ORR was <40% and indeterminate if in-between. Secondary outcomes included PET CR rate after 3 cycles of O-GDP and the rate of proceeding to ASCT. Exploratory outcomes included measurements of circulating tumor (ct) DNA during protocol therapy, and analysis of individual mutations. Results: The trial has completed its planned accrual of 30 patients. Median age was 59.5 (range 30 - 70), with 40% female, 70% with DLBCL NOS and 30% with transformed indolent lymphoma (all but one patient having transformed follicular lymphoma). IPI at study entry was 0-1 (20% of patients), 2 (30%) or 3+ (50%). Grade 3 or 4 toxicity was observed in 87% of patients. This was mainly myelosuppression with grade 4 neutropenia (47%) and thrombocytopenia (37%). Other grade 4 adverse events were sepsis (2 patients), febrile neutropenia (1 patient) and hypokalemia (1 patient). No grade 5 events were attributed to study treatment. One additional case of myelodysplastic syndrome caused treatment discontinuation. Events necessitating dose reductions (33% of patients), dose delays (23%) and dose holds (23%) occurred in a total of 57% of patients. At the time of submission, data are evaluable for the primary endpoint in 28 patients. The ORR (CR + PR) by CT imaging after 2 cycles of study therapy was 60.7% (95% CI 40.6-78.5) Overall, 65.5% of patients (95%CI = 45.7%-82.1%) proceeded to ASCT. In addition, 15 patients are evaluable by PET/CT after 3 cycles of O-GDP, with 47% attaining a complete metabolic response (Deauville 1 - 3), 40% a partial metabolic response and 13% with no metabolic response by Lugano criteria. Plasma ctDNA measurements were taken at baseline, after 1 cycle of O-GDP, and at the time of PET/CT. CtDNA quantities will be compared to imaging assessments. Conclusions: O-GDP is an outpatient salvage regimen that enables ASCT in patients with R/R DLBCL. Compared to R-GDP there is a greater frequency of grade 3 - 4 toxicity (O-GDP 87%, R-GDP previously reported at 47%), although the difference is mainly due to cytopenias and can be managed by dose adjustments to the GDP regimen. Further data analysis is required to determine if the trial will meet the primary endpoint of an ORR > 60%. The overall rate of proceeding to ASCT with O-GDP salvage in this trial was 65.5% compared to that previously reported for R-GDP at 51.9%. Disclosures Scott: NanoString: Patents & Royalties: Named Inventor on a patent licensed to NanoString Technologies, Research Funding; Roche: Research Funding; Janssen: Research Funding; Celgene: Consultancy, Honoraria. Kuruvilla:BMS: Consultancy, Honoraria; Abbvie: Consultancy; Leukemia and Lymphoma Society Canada: Research Funding; Seattle Genetics: Consultancy, Honoraria; Amgen: Honoraria; Celgene: Honoraria; Karyopharm: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Princess Margaret Cancer Foundation: Research Funding; Gilead: Consultancy, Honoraria; Lundbeck: Honoraria; Roche: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria.

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