A Prospective Phase II Comparison of Stem Cell Source Using Rituximab, Ifosfamide, Carboplatin, Etoposide (RICE) RE—Induction, Then High Dose Fludarabine, Busulfan (FLUBU) and Autologous (ASCT) or Allogeneic (AlloSCT) Hematopoietic Blood Stem Cell Transplantation for Mantle Cell (MCL) and Relapsed Low-Grade B-Cell Non-Hodgkin’s Lymphoma (NHL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 915-915
Author(s):  
Douglas A. Stewart ◽  
Michael Voralia ◽  
Ahsan Chaudhry ◽  
Oluyemi Jeje ◽  
Donald Morris ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell ◽  
Phase Ii ◽  
Blood Stem Cell ◽  
High Dose ◽  
Free Survival ◽  
Stem Cell Source ◽  
Cell Source ◽  
Prospective Phase ◽  
Grade 3

Abstract Introduction: A “genetically-randomized” prospective phase II study was designed to compare stem cell source following novel, uniform, and expected low toxicity re-induction and high dose chemotherapy for indolent B-cell NHL. Patients and Methods: Pts with MCL in 1st remission or 1st relapse, or other indolent B-cell lymphoma in 1st or 2nd relapse were eligible providing adequate organ function and age <65 years. Pts received RICE (Rituximab 375mg/m2 d1,8,15,22, Ifosfamide 1.67g/m2 d16-18, Carboplatin AUC=5 d17, Etoposide 100mg/m2 d16-18), with G-CSF d22-30, and apheresis d29-31 if ASCT, then FluBu (Fludarabine 50mg/m² d-6to-2, Busulfan 3.2 mg/kg IV daily d-5to-2) and SCT d0. GVHD prophylaxis for AlloSCT involved ATG 4.5mg/kg, MTX and CSA. Results: The initial 43 pts accrued from 06/2001-03/2004 included Follicular=30, MCL=7, SLL=4, other histology=2. Disease status was 1st remission=2, 1st relapse=18, 2nd relapse=12, 10 refractory=11. The median EFS following most recent prior chemotherapy was 7 mos. RICE resulted in an overall RR of 72%. Blood stem cell source was ASCT=27, donor SCT=16 (related=14, unrelated=1, syngeneic=1). For ASCT, a median of 5.9 (1–14.5) x106 CD34+ cells/kg were collected from 1 (n=17) or 2 (n=10) 15-25L aphereses. Three pts required a second mobilization procedure. 16/24 pts converted from positive to negative marrow biopsies post-RICE. Two pts had NHL detected in the autograft. FluBu resulted in no acute Bearman grade 3-4 RRT(overall 100d non-relapse mortality (NRM)=0% for both ASCT and donor SCT). Median engraftment times were slightly longer post AlloSCT than ASCT (ANC>0.5 = 15 vs 11d, and platelets>20 = 12 vs 9d, respectively). Of 15 AlloSCT pts, grade 3–4 aGVHD occurred in 5 (33%), cGVHD occurred in 64%, and death from extensive cGVHD + infection occurred in 5 pts from 7-13mo post-AlloSCT (overall NRM=33% for AlloSCT). With a median follow-up of 22mo, the 2 year projected outcome of ASCT vs Allo/Syngeneic-SCT for relapse-free survival (RFS) was 64% vs 87% (logrank p=0.48), event-free survival (EFS) 63% vs 52% (logrank p=0.38), and overall survival (OS) 86% vs 46% (logrank p=0.0018), respectively. For relapsed follicular lymphoma only, the 2yr EFS was 61% vs 59% (logrank p=0.49) and OS 100% vs 51% (logrank p=0.0009) for ASCT (n=19) vs Allo/Syngeneic SCT (n=11), respectively. Conclusion: These preliminary results suggest that RICE can "in-vivo" purge autografts but mobilizes blood stem cells only moderately well. RICE-FluBu/ASCT may result in prolonged EFS with significantly less NRM than AlloSCT.

A Phase II Study of Myeloablative I-131-Anti CD-20 (Tositumomab) Radioimmunotherapy and Autologous Hematopoietic Stem Cell Transplantation (ASCT) for Adults ≥60 Years of Age with High-Risk Relapsed or Refractory B-Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 487-487 ◽  
Author(s):  
Ajay K. Gopal ◽  
Joseph G. Rajendran ◽  
Ted A. Gooley ◽  
John M. Pagel ◽  
Darrell R. Fisher ◽  
...  
Keyword(s):  
Older Adults ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
B Cell ◽  
Cell Transplantation ◽  
Phase Ii ◽  
High Dose ◽  
Grade 3

Abstract The majority of patients with relapsed or refractory B-cell, non-Hodgkin’s lymphoma (NHL) are over 60 years of age, yet many are denied potentially curative high-dose regimens due to concerns of excessive toxicity with stem cell transplantation in this age group. Myeloablative anti-CD20 radioimmunotherapy (RIT) can deliver curative radiation doses to tumor sites while limiting exposure to normal organs and may be ideal for older adults requiring high-dose therapy. We have treated 24 patients with relapsed or refractory B-cell NHL aged ≥60 years using high-dose I-131-tositumomab (GlaxoSmithKline) and ASCT on a phase II trial. Patients were required to have a performance status of 0–1, acceptable organ function, ≥2x106 CD34+ cells/kg collected, and &lt;20 Gy prior radiation to critical organs. Patients with splenomegaly or tumor bulk over 500cc were required to undergo further cytoreduction or splenectomy in order to optimize biodistribution of the radiolabeled antibody. Patients without evidence of disease at the time of therapy were excluded. All pts underwent outpatient dosimetry using tositumomab (1.7 mg/kg) labeled with 5–10mCi I-131 followed by serial quantitative gamma camera imaging and patient and organ-specific dosimetry. Patients then received individualized infusions of I-131-tositumomab (1.7 mg/kg) to deliver 25–27Gy to the critical normal organ receiving the highest radiation dose followed by ASCT. Between 12/1/99 and 4/29/05 24 pts were enrolled on this study. Baseline characteristics included: median age at ASCT = 64 yrs (range 60–76 yrs), male = 15/24, median number of prior regimens = 4 (range 2–14), chemoresistant disease (defined as &lt; a partial response to the most recent regimen) = 13/24, Stage III/IV=100%, &gt;1 extranodal site = 21%, elevated LDH at treatment = 46%, IPI score at transplant 3–5 = 46%, Histology: diffuse large B-cell (DLBCL)=9 pts (with 4/9 transformed from follicular lymphoma [FL]), mantle cell (MCL)=8 pts, FL=6 pts, and marginal zone (MZL) 1 pt. The median I-131 activity administered was 525 mCi (range 328–1154 mCi) with dose limiting organs being lung, liver, and kidney in 12, 8, and 4 patients, respectively. The therapy was well tolerated with no treatment-related deaths, and no grade 3–4 Bearman toxicity. NCI CTC non-hematopoeitic toxicities by day 100 included: Grade 4=2/24 and Grade 3=17/24. The median time after ASCT for recovery of platelets &gt; 20K and neutrophils &gt;500 was 10 and 15 days, respectively. Sixteen of 24 pts remain alive (67%) and 10 (42%) are alive and progression-free with a median follow up from ASCT of 2.2 yrs (range 1 mo.–4.9 yrs.) for survivors. The estimated 3-year overall and progression-free survival are 56% and 37%, respectively. Surviving patients include 6/8 with MCL, 5/7 with FL/MZL, and 5/9 with DLBCL as well as 9/13 with chemoresistant disease. Myeloablative I-131-tositumomab with ASCT is a well-tolerated and effective transplant option for older adults with high-risk, relapsed B-NHL, though longer follow-up and additional pts will be needed to confirm the reproducibility and durability of these findings.

Intensive sequential chemotherapy with repeated blood stem-cell support for untreated poor-prognosis non-Hodgkin's lymphoma.

1997 ◽  
Vol 15 (5) ◽  
pp. 1722-1729 ◽  
Author(s):  
A M Stoppa ◽  
R Bouabdallah ◽  
C Chabannon ◽  
G Novakovitch ◽  
N Vey ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Duration ◽  
Hodgkin’S Lymphoma ◽  
Dose Intensity ◽  
Blood Stem Cell ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Sequential Chemotherapy ◽  
Free Survival ◽  
Non Hodgkin's Lymphoma

PURPOSE To demonstrate the feasibility and efficacy of six ambulatory high-dose sequential chemotherapy courses that include three intensified cycles supported by stem-cell infusion in high-risk and high-intermediate-risk untreated non-Hodgkin's lymphoma (NHL) patients. PATIENTS AND METHODS A pilot nonrandomized study included 20 untreated patients aged less than 60 years with aggressive histologically identified NHL and two or three adverse-prognosis criteria (International Index). Patients received an ambulatory regimen with high-dose chemotherapy supported by granulocyte colony-stimulating factor (G-CSF) and repeated peripheral-blood stem-cell (PBSC) infusion. The median age was 39 years (range, 20 to 59), with 13 men and seven women. Chemotherapy consisted of one cycle every 21 days for a total of six cycles. The first three cycles (A1, A2, and A3) consisted of cyclophosphamide (Cy) 3,000 mg/m2, doxorubicin (Doxo) 75 mg/m2, and vincristine 2 mg (plus corticosteroids). The last three cycles (B4, B5, and B6) consisted of the same drug combination plus etoposide 300 mg/m2 and cisplatin 100 mg/m2. For an expected duration of 18 weeks, the projected dose-intensity was 25 mg/m2/wk for Doxo and 1,000 mg/m2/wk for Cy. G-CSF 300 micrograms was administered from day 6 following each cycle until neutrophil reconstitution. Two aphereses were performed at approximately day 13 after each A cycle, and PBSCs were injected at day 4 of each B cycle. Radiotherapy on tumor masses > or = 5 cm was scheduled after completion of the last cycle. RESULTS The median duration of grade 4 neutropenia was 1 day (range, 0 to 7) for each A cycle and 4 days (range, 1 to 10) for each B cycle (P = .02). The median duration of grade 4 thrombopenia was 0 days (range, 0 to 8) for each A cycle and 6 days (range, 1 to 21) for each B cycle (P < .001). Hospitalization for febrile neutropenia was required for 18% and 44% of patients during cycles A and B, respectively (P < .01). Only three patients did not complete the protocol: one due to emergency surgery after cycle B4, one who died after cycle B5 from interstitial pneumonia, and one with delayed hematologic reconstitution after cycle B4. Chemotherapy delivery was optimal (median actual relative dose-intensity, 97%; range, 66 to 100). The median total dose administered over 18 weeks was 18,000 mg Cy (range, 12,000 to 18,000), 450 mg Doxo (range, 300 to 450), 900 mg etoposide (range, 300 to 900), and 300 mg cisplatin (range, 100 to 300). Evaluation of response after six courses showed 13 complete remissions ([CRs] 65%), four partial remissions (PRs), two nonresponses (NRs), and one toxic death. With a median follow-up period of 25 months (range, 16 to 43), 15 patients are alive, with 12 in continuous first CR; five patients relapsed (four of four PRs and one of 13 CRs). Two-year survival and failure-free survival (FFS) rates are 73% and 56%, respectively. The disease-free survival (DFS) rate for the CRs is 86%. CONCLUSION PBSC support contributes to the feasibility of first-line, very-high-dose, ambulatory chemotherapy delivery in poor-risk NHL and is associated with a high rate of remission and FFS.

Long Term Follow-Up of 4-Hydroperoxycyclophosphamide Purged Autologous Bone Marrow Transplantation in Non-Hodgkin’s Lymphoma Patients with High Risk of Bone Marrow Involvement.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5234-5234
Author(s):  
Elise A. Chong ◽  
Charalambos Andreadis ◽  
Stephen J. Schuster ◽  
Selina M. Luger ◽  
David L. Porter ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
High Risk ◽  
B Cell ◽  
Tumor Cells ◽  
Platelet Transfusion ◽  
High Dose ◽  
Free Survival

Abstract Introduction: High-dose chemotherapy and autologous stem cell transplant (ASCT) can result in long term survival for patients with advanced non-Hodgkin’s lymphoma (NHL) but relapse remains a common cause of treatment failure. Bone marrow (BM) involvement is common in NHL and there is controversy over whether or not reinfusion of BM stem cells contaminated by clonogenic tumor cells is a major cause of relapse following ASCT. Bone marrow purging can reduce the number of tumor cells in vitro, but the impact on relapse and disease free survival (DFS) remains unknown. Methods: Between 1990 and 1993, 20 pts with poor prognosis NHL (B-symptoms, high LDH, bulky adenopathy, stage III or IV, or relapsed disease) at high risk for BM involvement underwent 4-hydroperoxycyclophosphamide (4-hc) purged BM transplantation. Thirteen pts had low grade B-cell NHL, 6 had an intermediate grade B-cell NHL with a small B-cell component, and 1 had T-lymphoblastic lymphoma. Seven of 20 pts had received ≥3 prior chemotherapeutic regimens. Three pts underwent transplantation in first complete remission and 17 pts were in chemotherapy-responsive relapse. At diagnosis, 11 of 20 pts had documented BM involvement, and at ASCT, 6 of 20 pts had BM involvement (all < 5% involvement at BM harvest). Eighteen pts (90%) received 4-hc purged autologous BM, and 2 pts (10%) received 4-hc purged autologous BM and peripheral stem cell support. High dose regimens included Cytoxan/TBI (85%), BCV(10%), and Melphalan/TBI (5%). The median age was 45 yrs (range: 20–57 yrs). The median nucleated cell count of 4-hc marrow that was reinfused was 2.4 × 108 /kg (range: 0.87–5.5). The median time to granulocyte recovery was 26 days (range: 14–59). Two pts died at days 31 and 35 without achieving platelet transfusion independence. In the remaining 18 pts, the last platelet transfusion was given at a median of 29 days post-marrow infusion (range 18–149), and the median in-patient hospital days was 27 (range: 16–82 days). Results: There were 2 deaths (fungal infection and CNS relapse) during ASCT. One pt died in CR after developing secondary AML 5.34 yrs after ASCT. Post-ASCT, 18 of 20 pts achieved CR (including 1 pt who had no evidence of disease at autopsy), 1 pt had a PR, and 1 pt died during BMT and was not evaluable for response. Median follow-up for the group was 8.2 yrs (range: 0.1–12.4 yrs). At last follow-up, 9 pts remain in CR (1 died of AML in CR), 5 pts had relapsed and remain alive, and 5 pts died of progressive disease. Median follow-up for survivors was 11.1 yrs (range: 5.2–12.4 yrs). 65% of pts remain alive at last follow-up. The median EFS was 9.4 yrs (range: 0.1–12.4 yrs). Those who achieved a CR post-ASCT had a median DFS of 10.6 yrs (range: 1.1–12.4 yrs). At 8.2 yrs, 4/6 pts with involved BM at the time of harvest had relapsed or died compared to 7/14 pts with negative BM which is not significantly different. Conclusion: ASCT using 4-hc BM purging is feasible and can result in long term relapse free survival, even for pts with subtypes of NHL at high risk for BM involvement. Whether 4-hc BM purging is equivalent or superior to immunologic approaches to stem cell processing remains to be determined.

A Prospective, Randomized, Phase III Study of Melphalan 200 mg/m2 (MEL200) Versus Melphalan 100 mg/m2 (MEL100) in Newly Diagnosed Myeloma Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 55-55 ◽  
Author(s):  
Antonio Palumbo ◽  
Sara Bringhen ◽  
Maria Teresa Petrucci ◽  
Antonietta Falcone ◽  
Anna Marina Liberati ◽  
...  
Keyword(s):  
Stem Cell ◽  
Adverse Events ◽  
Response Rate ◽  
Complete Response Rate ◽  
Complete Response ◽  
Phase Iii ◽  
Psychiatric Disease ◽  
High Dose ◽  
Free Survival ◽  
Grade 3

Abstract Several trials have shown the superior impact of high-dose melphalan (usually 200 mg/m2, MEL200) versus standard therapy in myeloma patients. Intermediate-dose melphalan (100 mg/m2, MEL100) was also superior to the standard dose, but MEL100 has not been clinically compared with MEL200 in a randomized study. In a case-matched study, response rate and event-free survival of MEL200 were superior to MEL100, but overall survival (OS) was similar. In this prospective, randomized, phase III trial, we compared the efficacy and toxicity of MEL200 and MEL100. Between January 2002 and July 2006, 299 patients were enrolled. Inclusion criteria were previously untreated myeloma, aged < 65 and Durie and Salmon stage II or III. Exclusion criteria were abnormal cardiac function, respiratory disease, abnormal liver function, abnormal renal function, HBV, HCV, or HIV positivity, concomitant cancer or psychiatric disease. The institutional review board approved the protocol and written informed consent was obtained from all patients. All patients received: 2 dexamethasone-doxorubicin-vincristine debulking courses (doxorubicin 50 mg/m2 day 1, vincristine 1 mg day 1, dexamethasone 40 mg days 1, 2, 3, 4, each course repeated every 28 days), 2 cycles of cyclophosphamide (4 g/m2, day 1) plus G-CSF followed by stem cell harvest. The MEL200 group was conditioned with 2 cycles of melphalan 200 mg/m2 followed by stem cell reinfusion; the MEL100 group was conditioned with 2 courses of melphalan 100 mg/m2 followed by stem cell reinfusion. At the present, 246 patients, median age 57 (range 32–65), completed the assigned therapy and were evaluated for response, progression-free survival (PFS) and OS. One-hundred and twenty-four patients were randomized to MEL200 and 122 to MEL100. Patient characteristics were similar in both groups. Abnormal cytogenetics (13q deletion, t(4;14), t(11;14), p53) were 75% in MEL200 patients and 56% in MEL100 patients (p=0.05). Forty-six patients did not complete tandem MEL200; 36 patients did not complete tandem MEL100. The near complete response rate of MEL200 was superior to MEL100 (32% versus 18%, p=0.011), but partial response was 80% versus 71%, respectively (p=0.079). The median follow-up for censored patients was 26.5 months. The 3 years PFS was 51% in the MEL200 arm and 33% in the MEL100 arm (HR=0.81, 95% CI 0.55–1.21, p=0.31). The 3 years OS was 86% in the MEL200 group and 71% in the MEL100 group (HR=0.82, 95 CI 0.45–1.48, p=0.51). Duration of grade 4 neutropenia and thrombocytopenia was comparable in two arms, but MEL200 patients required more platelet transfusions (p=0.03). Grade 3–4 non-hematological adverse events were reported in 49% of the MEL200 patients and in 38% of the MEL100 patients (P=0.07). The most frequent grade 3–4 adverse events were infections (54% of MEL200 patients versus 45% of MEL100 patients, p=0.25), mucositis (31% of MEL200 patients versus 7% of MEL100 patients, p=0.002) and gastrointestinal toxicities (20% of MEL200 patients versus 14% of MEL100 patients, p=0.3). In conclusion, MEL200 resulted in a significantly higher near complete response rate but this did not translate in a superior PFS and OS.

Allogeneic Stem Cell Transplantation for Relapsed Follicular Non-Hodgkin’s Lymphoma: Single Centre Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5054-5054
Author(s):  
Amir Peyman ◽  
Stephen Couban ◽  
Kara Thompson ◽  
Louis Fernandez ◽  
Donna L. Forrest ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Grade 3

Abstract Between 1993 and 2005, 57 patients with follicular lymphoma underwent high-dose chemo/radiotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), 49 Allogeneic, (16 Bone Marrow and 33 Peripheral Blood), 6 MIN, 2 MUD. Median age was 47 years. Median days to neutrophil and platelet engraftment after HSCT were 18 and 13 days respectively. Twenty-five patients experienced Acute GVHD and thirty-four had Chronic GVHD (12 mild and 22 extensive). Thirty-three patients were in grade 1, 17 in grade 2, 4 in grade 3 and 3 grade 4. As of their FLIPI score, 4, 14, 21 and 18 patients were calculated to have score of 0, 1, 2 and 3 respectively. Forty-one patients are alive. Two patients have relapsed, one a year and the other two years after HSCT. The 5 year survival was 71.9% (95% CI 57.5–82.2%) and 5 year survival was 67.2% (95% CI 52.3–78.5%). Transplant related mortality rate (TRM) in 5 year was 22.4% (95% CI 63.6–86.8%). No significant differences was found among FLIPI groups 0,1,2 and 3 in terms of overall, relapse-free survival, TRM Allogeneic HSCT for patients with progressive follicular lymphoma is feasible and may result in prolonged disease-free survival.

Impact of Cyclosporine a (CsA) Concentration on the Incidence of Severe Acute Graft-Versus-Host Disease (GVHD) after Allogeneic Stem Cell Transplantation (allo-SCT).

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1150-1150
Author(s):  
Florent Mallard ◽  
Eolia Brissot ◽  
Patrice Chevallier ◽  
Thierry Guillaume ◽  
Jacques Delaunay ◽  
...  
Keyword(s):  
Stem Cell ◽  
Blood Concentration ◽  
Acute Gvhd ◽  
Conditioning Regimen ◽  
Solid Organ ◽  
Stem Cell Source ◽  
Cell Source ◽  
Trough Blood ◽  
Grade 3 ◽  
Severe Grade

Abstract CsA is widely used as the backbone immunosuppressive agent for GVHD prevention after allo-SCT. Previous studies have demonstrated that the immunosuppressive effects of CsA (eg. inhibition of calcineurine in lymphocytes) may be correlated with CsA blood concentration, especially in the context of solid organ transplantation. This report aimed to investigate the impact of CsA concentrations in the early post allo- SCT period, on the incidence of severe acute GVHD, in 85 consecutive patients treated in a single centre between Jan. 2006 and Jan. 2008, and for whom CsA concentrations in the blood were monitored weekly after the start of infusion. 85 patients (45 males) received CsA (usually at 3 mg/Kg/d, 2 or 3 days prior to graft infusion) as a 24-h continuous infusion until hematopoietic recovery and switch to oral formulation. Dose modifications of CsA were performed to maintain adequate trough blood levels and to prevent nephrotoxicity. Patients’ and donors characteristics were as follow: median age: 51 (range, 18–67), 46 (54%) female donors, 33 (39%) myeloid malignancies, 49 (58%) lymphoid malignancies, and 3 cases of SAA. The stem cell source was PBSC in 66 (78%) patients, while bone marrow was used in 19 (22%) patients. 37 (43.5%) were transplanted from a matched related donor, and 48 (56.5%) from a matched unrelated donor. A myeloablative conditioning regimen was used in 24 (28%) patients, and 61 (72%) received a reduced intensity regimen. The median concentrations of CsA in the blood at 1, 2, 3 and 4 weeks after allo-SCT were 348 (range, 172–733), 284 (range, 137–535), 274 (range, 107–649), and 247 (37–695) ng/mL respectively. All patients engrafted at a median of 17 (range, 0–42) days after allo-SCT. With a median follow-up of 16 (range, 5–29) months, grade 2–4 acute GVHD occurred in 36 patients (42%) at a median of 29 (range, 6–100) days after allo-SCT. The incidence of severe grade 3–4 acute GVHD was 23% (95%CI, 14–32%). In this cohort, all acute GVHD risk factors (age, donor-recipient gender, CMV serostatus, ABO compatibility, diagnosis, disease status, stem cell source, donor type, conditioning regimen type, GVHD prophylaxis regimen, CsA concentrations) were assessed. In multivariate analysis, we found that higher whole-blood CsA concentration in the first week following graft infusion, and before onset of acute GVHD was the strongest parameter significantly associated with a reduced the risk of severe grade 3–4 acute GVHD (P=0.01; RR=0.24; 95%CI, 0.08–0.73). Despite its retrospective nature, these data strongly indicate a close relationship between CsA trough blood concentration during the early post allo-SCT period and the severity of acute GVHD. Inadequate or insufficient early exposures of CsA can be a serious risk for developing severe acute GVHD. Therefore, precise monitoring of CsA concentrations and achievement of a high CsA target concentration may be an effective tool to prevent the onset of severe acute GVHD.

Prospective phase II study of sunitinib rechallenge in metastatic renal cell carcinoma (mRCC): A G.I.O.N. trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16081-e16081 ◽  
Author(s):  
Camillo Porta ◽  
Vittorio D. Ferrari ◽  
Paolo Andrea Zucali ◽  
Giuseppe Fornarini ◽  
Antonio Bernardo ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Cross Resistance ◽  
Stage Design ◽  
Free Survival ◽  
Prospective Phase ◽  
Grade 3

e16081 Background: Sunitinib is a 1st-line standard of care in mRCC. Lack of cross-resistance to sequential VEGF-targeting drugs and the possibility of a successful rechallenge with Sunitinib have been postulated. Whether mRCC patients (pts) could benefit from rechallenge with Sunitinib after progressing on 1st-line Sunitinib and 2nd-line Everolimus was the aim of this phase II study Methods: 39 mRCCpts were prospectively treated with Sunitinib (50 mg/daily, 4:2); main inclusion criteria were: histologically proven RCC with clear cell component, previous 1st-line Sunitinib with a Disease Control Rate lasting at least 10 months, 2nd-line Everolimus, and written informed consent. The primary end-point of this study was 6-months progression-free survival (PFS). A Simon’s 2-stage design was used; after testing Sunitinib on 12 pts in the first stage, the trial would have been terminated if 5 or fewer had a PFS of less than 6 months. Otherwise, the trial would have proceeded to the second stage, enrolling a total of 38 pts. If the total number of pts free of progression at 6 months would have been less than or equal to 18, Sunitinib would have been rejected Results: As a whole, 39 pts (30 males, 9 females) were enrolled. The study quickly moved from the first stage to its completion and ultimately succeeded; indeed, 6-months PFS was 60%, median PFS being 8.6 months (average: 9.59, range: 0.7-24.6 months). In terms of safety no unexpected toxicities were observed. Tx-related grade 3-4 AEs observed in ≥5% of the pts were: hand-foot skin reaction, fatigue, nausea, hypertriglyceridemia, hypophosphatemia, hypocalcemia, hyperglycemia, and neutropenia. One case each of myocardial infarction, atrial flutter and spontaneous pneumothorax were also reported, but resolved Conclusions: Despite an ineluctable time-lead-bias, median PFS on Sunitinib rechallenge was high (8.6 months), clearly showing that many pts may become sensitive again to VEGFRs-inhibition. Although many agents are presently available from 2nd-line on, in countries where treatment options are still limited, Sunitinib rechallenge could still represent a reasonable treatment option. EudraCT number: 2012-000473-23. Clinical trial information: 2012-000473-23.

scholarly journals Bortezomib Maintenance Therapy after Induction with R-CHOP, ARA-C and Autologous Stem Cell Transplantation in Newly Diagnosed MCL Patients, Results of a Multicenter Phase II HOVON Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 339-339 ◽  
Author(s):  
Jeanette K Doorduijn ◽  
Monique C. Minnema ◽  
Marie Jose Kersten ◽  
Pieternella J Lugtenburg ◽  
Martin R. Schipperus ◽  
...  
Keyword(s):  
Stem Cell ◽  
Maintenance Therapy ◽  
Phase Ii ◽  
Research Funding ◽  
Progressive Disease ◽  
Induction Treatment ◽  
High Dose ◽  
Newly Diagnosed ◽  
Grade 3

Abstract Introduction. The standard first-line treatment of young and fit mantle cell lymphoma (MCL) patients consists of a rituximab containing induction of CHOP and high dose ARA-C, followed by high dose consolidation and autologous stem cell transplant (ASCT). Thus far, almost all patients relapse after ASCT. Bortezomib is a proteasome inhibitor with activity in MCL. We investigated in a randomized phase II study whether there was any indication that maintenance therapy with bortezomib after ASCT could improve the outcome of treatment, measured as event free survival (EFS). Methods. Patients 18-65 years with newly diagnosed MCL were treated with 3 cycles of R-CHOP and 2 cycles of ARA-C (2 x 2 g/m2 iv d1-4) and rituximab (375 mg/m2, iv d11). Patients in PR or CR continued with ASCT after BEAM conditioning. Patients with a PR or CR after ASCT, with a neutrophil count > 0.5 x 109/l and platelets > 80 x 109/l were randomized between bortezomib and no further treatment. Bortezomib 1.3 mg/m2 iv was given once every two weeks, for 2 years, starting between 6 - 12 weeks after transplantation. Results . Between October 2007 and February 2012, 140 patients aged 34-66 years (median 57) were registered. Five patients were not eligible. The MIPI score was low, intermediate, high or unknown in 57%, 32%, 10% and 1% respectively. All eligible patients started induction treatment with R-CHOP. Two patients did not receive the first ARA-C cycle, because of progressive disease and physician decision. Hundred-fifteen patients (85%) received the BEAM and ASCT. Reasons to stop protocol treatment before ASCT were: progressive disease (PD) (n=6), inadequate stem cell harvest (n=3), excessive toxicity (n=3), other reasons (n=8). The response after ASCT was CR/CRu in 99 patients (86%), PR in 15 (13%), unknown in 1 (1%). Only 62 patients (45%), aged 34-65 years (median 56) were randomized between bortezomib maintenance and no further treatment. Two patients were randomized, but not eligible. Reasons for no randomization were: not eligible (n=30), patient refusal (n=14), excessive toxicity (n=2, and other reasons (n=7). In each treatment arm 30 patients were included. The patient characteristics were well balanced, except the MIPI score. In the no maintenance arm 21 patients (70%) had a low MIPI, compared to 15 patients (50%) in the bortezomib arm, and 6 (20%) versus 11 (37%) patients had an intermediate MIPI score. In both arms 3 patients (10%) had a high MIPI. Fifteen patients (50%) in the maintenance group continued bortezomib for 2 years. Reasons to stop earlier were excessive toxicity (n=6), PD/relapse (n=4), patients refusal (n=3) and other (n=2). The main adverse events during maintenance therapy were neurologic (CTC grade 2: 14%, grade 3: 4%), and infectious (grade 2: 11%, grade 3: 7%). Three patients developed a secondary malignancy: a basal cell carcinoma in the no maintenance group, a melanoma and a prostate carcinoma in the bortezomib group. With a median follow-up of the patients still alive of 50.9 months EFS at 4 years for all patients is 61%, and the overall survival (OS) 78%. The median follow-up of the randomized patients still alive is 42.9 months. The EFS at 4 years is 72% without maintenance versus 71% in the patients randomized for bortezomib maintenance. The OS at 4 years also shows no significant difference between the groups, 90% versus 93% respectively. Conclusion. There is no indication that bortezomib iv maintenance in a frequency of once every 2 weeks does improve the EFS of newly diagnosed MCL patients after intensive induction treatment with R-CHOP, double ARA-C and BEAM followed by ASCT. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Doorduijn: Celgene: Consultancy; Janssen: Consultancy; Roche: Consultancy. Off Label Use: bortezomib maintenance in MCL. Minnema:Celgene: Consultancy; Jansen Cilag: Consultancy; Amgen: Consultancy. Kersten:janssen: Honoraria, Research Funding; takeda millennium: Research Funding; roche: Honoraria, Research Funding. Lugtenburg:Mundipharma: Consultancy; Servier: Consultancy; Janssen-Cilag: Consultancy; Celgene: Consultancy; Roche: Consultancy. Schipperus:Novartis: Consultancy. Zijlstra:Celgene: Consultancy; Roche: Consultancy.

Haploidentical Hematopoietic Stem Cell Transplantation In Hematologic Malignancies with G-CSF Mobilized Bone Marrow Plus Peripheral Blood Stem Cells Grafts without T Cell Depletion: a Single Center Report of 29 Cases

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3552-3552
Author(s):  
Hengxiang Wang ◽  
Hongmin Yan ◽  
Zhidong Wang ◽  
Mei Xue ◽  
Ling Zhu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Blood Stem Cell ◽  
Hematopoietic Stem ◽  
Platelet Recovery ◽  
Stem Cell Source ◽  
Cell Source

Abstract Abstract 3552 Introduction: Haploidentical Hematopoietic stem cell transplantation (Haplo-HSCT) has provided an alternative option since virtually all patients have an immediately available donor. In order to reduce the occurrence of severe acute GVHD, initially we used donor bone marrow with G-CSF mobilization as hematopoietic stem cell source and achieved good effect. However, as this work carried out widely, it is difficult to collect enough bone marrow cells from donor due to the much differences body weight between the recipient and donor, and lead to patients with hematopoietic recovery slowly. From February 2003 we started trying to use bone marrow and peripheral blood stem cell as stem cell source. Patients and Methods: Twenty-nine patients with hematologic malignancies were enrolled in this study between February 2003 and August 2007 at the general hospital of air force. Conditioning regimen consisting of high-doses of cytarabine and cyclophosphamide with total body irradiation, while 6 cases were preconditioned with busulfan, cytarabine and cyclophosphamide. aGVHD was prevented by a combination of immunosuppressive drugs including a monoclonal antibody against human CD25 (basiliximab), cyclosporine A (CsA), methotrexate (MTX), mycophenolate mofetil (MMF), and a rabbit anti-thymocyte globulin. Donors were given G-CSF at a dose of 300μg daily for 6 consecutive days prior to marrow harvesting. Peripheral blood stem cell was collected on the 7th day. Results: All patients attained successful neutrophil and platelet recovery. The median time to neutrophil engraftment was 17.1days, and that of platelet recovery was 20.9 days. The incidence of grade II-‡W GVHD was 31.03% and grade III-‡W GVHD was 13.79%. The GVHD-related death was 3.45%. The incidence of cGVHD was 48.2%. The incidence of extensive cGVHD was 23.3%. The incidence of diseases relapsed was 13.79%. A median follow-up of 54 months noted that 13 patients died, while 16 survived. The total disease-free survival rate longer than 3 years was 55%. Conclusion: G-CSF mobilization bone marrow and peripheral blood stem cell as stem cell source for Haplo-HSCT provided rapid and sustained engraftment without increase of severity GVHD. The rate of disease relapse was reduced. This treatment was particularly suitable for patients with heavier weight. Disclosures: No relevant conflicts of interest to declare.

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