Autologous Stem Cell (AUTO) vs Non-Myeloablative Allogeneic Transplantation (NMT) after High-Dose Rituximab (HD-R) -Containing Conditioning Regimens for Relapsed Chemosensitve Follicular Lymphoma (FL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 48-48 ◽  
Author(s):  
Issa F. Khouri ◽  
Rima M. Saliba ◽  
Chitra M. Hosing ◽  
Sandra A. Acholonu ◽  
Luis E. Fayad ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Control Group ◽  
High Dose ◽  
Unrelated Donor ◽  
Study Group ◽  
Significant Difference ◽  
Risk Of Progression

Abstract We evaluated the safety and efficacy of NMT vs. AUTO as a treatment modality for patients (pts) with relapsed chemosensitive FL. Pts were considered for AUTO if they did not have a matched sibling donor. Pts were eligible for NMT if they had a donor, especially if pts were > 1st relapse or failed a prior AUTO. Between March 1999 and April 2005, 68 consecutive pts were treated. 47 received a NMT after conditioning with fludarabine, cyclophosphamide, HD-R (Blood89:3595, 2001). Twenty-one other pts received AUTO after either Cy/TBI/HD-R (N=8) or BEAM/HD-R (N= 13) (JCO23:2240,2005). The HD-R regimen consisted of 2 injections pre-transplant in NMT or during cell mobilization for AUTO, at 375 mg/m2 and 1000 mg/m2, respectively. Pts then received two additional doses of 1000 mg/m2 at days +1 and +8 post-transplant. Median age of pts (53 yrs), time from diagnosis to transplant (3yrs), % pts in PR (57%) at study entry were equal in both groups. There was no statistically significant difference in gender distribution, histology subtypes of FL grades, history of marrow involvement, beta-2 microglobulin (b2-m), IPI and LDH levels between the two groups. There were however more pts in the NMT group who had > 1 relapse (38% vs 19%, P = 0.09), or had > 3 lines of therapy (28% vs none). Eight pts (17%) in the NMT group had failed a prior AUTO. Sixty-six pts (97%) had peripheral blood (PB) transplant, two other pts with NMT received marrow from an unrelated donor. With a median follow-up time of 34 months, overall survival rates at 3-year were 88% and 84% for the NMT and AUTO groups, respectively (P=0.8). DFS and risk of progression were comparable between the two groups (85% vs 84%, and 3% vs 5%, respectively). DFS for the 8 pts who received NMT after failing a prior AUTO was 87% at 4-year. Causes of death varied between the AUTO group [Secondary leukemia (2), viral encephalitis (1)] and the NMT group [acute GVHD (2), chronic GVHD (2), unknown (1)]. We compared the outcome of AUTO in this study [AUTO Study Group), to a historical group [AUTO Control Group] of pts who received an AUTO under an immediately preceding protocol (years of therapy: 1994-1998). Pts in the AUTO Control Group were younger [Median age was 47 vs. 53 yrs, respectively, P = 0.007)], received Cy/VP-16/TBI without HD-R as conditioning regimen, and mostly (84% of pts) received in-vitro purged marrow as the source of graft (P < 0.001). Other disease characteristics were not statistically different between them. Results at 3-years demonstrated a higher risk of progression in the AUTO Control Group compared to the AUTO Study Group (26% vs. 5%, respectively, P = 0.09), an inferior DFS (58% vs. 84%, respectively, P = 0.04), and a tendency for a shorter survival (74% vs 84%, respectively, P = 0.2). These data suggest that NMT has a spectrum of safety that becoming comparable to AUTO. HD-R appears to improve the outcome after AUTO. Longer follow-up is needed to assess remission duration in the 2 study groups. A prospective controlled trial of AUTO vs. NMT using HD-R in each arm is warranted to assess the optimal strategy for treatment of relapsed FL.

Unrelated Donor Hematopoietic Cell Transplantation after Non-Myeloablative Conditioning for Patients with High Risk Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3158-3158
Author(s):  
Roberto Sorasio ◽  
Luisa Giaccone ◽  
Francesca Patriarca ◽  
Vittorio Montefusco ◽  
Stefano Guidi ◽  
...  
Keyword(s):  
Disease Progression ◽  
Initial Treatment ◽  
Response Rate ◽  
Treatment Plan ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
High Response ◽  
High Dose ◽  
Unrelated Donor

Abstract Allografting can induce long-term molecular remissions and possibly cure in myeloma patients. The recent development of non-myeloablative conditionings has reduced the transplant-related mortality (TRM) typically associated with myeloablation and extended the eligible age for transplantation. Moreover, high response rates are reported especially when allografting is preceded by cytoreductive high dose chemotherapy. We investigated the feasibility of unrelated donor non-myeloablative transplantation as either part of the initial treatment plan or as salvage treatment in heavily pre-treated patients. Twenty-two patients underwent non-myeloablative allografting, 10 as part of their initial treatment and 12 at disease relapse. Donors were matched for HLA-A, B, C, DRB1 and DQB1 by high-resolution typing. Only one single class I allele disparity was allowed. Conditioning regimen consisted of fludarabine 90 mg/m2 and 2 Gy total body irradiation. GVHD prophylaxis included oral cyclosporine (CyA) and mycophenolate mofetil (MMF). CyA was administered at 6.25 mg/Kg every 12 hours from day -3; levels were targeted to the upper therapeutic range (450–500 ng/ml, Abbott TDX, Abbott Park, IL) for the first month post-transplant. In the absence of GVHD, CyA was tapered from day +100 and discontinued on day +177. MMF was administered from day 0 after PBSC infusion to day +40 at 15 mg/Kg every 8 hours, and then tapered till day +96. Twenty/22 (91%) patients readily engrafted. Two patients experienced graft failure and eventually recovered autologous hematopoiesis. After a median follow up of 11 months (3–27), TRM was 18% and 16/22 patients (73%) are alive. Deaths occurred in 10% of patients transplanted upfront and in 42% of those transplanted at relapse: 3 patients died from infections, 1 from hemolytic uremic/ thrombotic thrombocytopenic purpura syndrome, and 2 from disease progression (both were transplanted at relapse). Ten/20 engrafted patients (50%) had grade II–IV acute GVHD (10% grade III–IV), and 59% had extensive chronic GVHD. Overall response rate was 60% (including 20% CR): 78% in patients transplanted upfront (no disease progression observed) and 45% in those transplanted at relapse. In the two groups, progression-free and one year event-free survival were 100% and 44% (p<0.025), and 90% and 28% respectively (p<0.005). Unrelated donor non-myeloablative allografting is feasible with relatively low TRM and high response rate. Graft-versus-myeloma effect appears to be more efficient when patients are treated soon after diagnosis. Longer follow-up is needed to assess response duration.

Capsular closure versus unrepaired interportal capsulotomy after hip arthroscopy in patients with femoroacetabular impingement, results of a patient-blinded randomised controlled trial

2021 ◽  
pp. 112070002110057
Author(s):  
Niels H Bech ◽  
Inger N Sierevelt ◽  
Sheryl de Waard ◽  
Boudijn S H Joling ◽  
Gino M M J Kerkhoffs ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Femoroacetabular Impingement ◽  
Hip Arthroscopy ◽  
Controlled Trial ◽  
Poor Quality ◽  
Control Group ◽  
Treatment Groups ◽  
Significant Difference ◽  
Randomised Controlled

Background: Hip capsular management after hip arthroscopy remains a topic of debate. Most available current literature is of poor quality and are retrospective or cohort studies. As of today, no clear consensus exists on capsular management after hip arthroscopy. Purpose: To evaluate the effect of routine capsular closure versus unrepaired capsulotomy after interportal capsulotomy measured with NRS pain and the Copenhagen Hip and Groin Outcome Score (HAGOS). Materials and methods: All eligible patients with femoroacetabular impingement who opt for hip arthroscopy ( n = 116) were randomly assigned to one of both treatment groups and were operated by a single surgeon. Postoperative pain was measured with the NRS score weekly the first 12 weeks after surgery. The HAGOS questionnaire was measured at 12 and 52 weeks postoperatively. Results: Baseline characteristics and operation details were comparable between treatment groups. Regarding the NRS pain no significant difference was found between groups at any point the first 12 weeks after surgery ( p = 0.67). Both groups significantly improved after surgery ( p < 0.001). After 3 months follow-up there were no differences between groups for the HAGOS questionnaire except for the domain sport ( p = 0.02) in favour of the control group. After 12 months follow-up there were no differences between both treatment groups on all HAGOS domains ( p  > 0.05). Conclusions: The results of this randomised controlled trial show highest possible evidence that there is no reason for routinely capsular closure after interportal capsulotomy at the end of hip arthroscopy. Trial Registration: This trial was registered at the CCMO Dutch Trial Register: NL55669.048.15.

scholarly journals Effectiveness of Antipyretic with Tepid Sponging Versus Antipyretic Alone in Febrile Children: A Randomized Controlled Trial

2018 ◽  
Vol 37 (2) ◽  
pp. 129-133
Author(s):  
Chetak Kadbasal Basavaraj ◽  
Shyamala Gowri Pocha ◽  
Ravi Mandyam Dhati
Keyword(s):  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
Control Group ◽  
Study Group ◽  
Axillary Temperature ◽  
Medical College ◽  
Randomized Controlled ◽  
Significant Difference

Introduction: Fever is the most common presenting complain for which children are brought to the paediatrician.Physical methods are widely used in treating febrile children, tepid sponging being commonly practiced in hospitals along with antipyretics. The objectives of this study were to compare the effectiveness of tepid sponging and antipyretic drug versus antipyretic drug alone in febrile children.Material and Methods: This was a Randomized controlled trial done in JSS Medical College and Hospital. All children under the age of 6 months to 12 years, admitted with axillary temperature of >99oF were included in the study. A total of 500 children were included over two years study period. Children with recorded axillary temperature of >990F were randomized into control and study group by computer generated randomisation. Children in the control group received only paracetamol (15mg/kg) at 5 minutes and combined group received paracetamol and tepid sponging at five minutes. Axillary temperature was monitored every 15 minutes for a period of 2 hours in both the groups.Results: There is no significant difference in reduction of temperature between the two groups by the end of two hours. Children in combined group had a higher level of discomfort than those in only antipyretic group.Conclusion: Tepid sponging does not add to the efficacy of paracetamol in antipyresis and that addition of tepid sponging to antipyretic, results in additional discomfort for the child. This study, therefore, endorses the view that antipyretic alone without tepid sponging should be the modality of therapy in children with fever.  

scholarly journals A Randomized Controlled Trial of Conbercept Pretreatment before Vitrectomy in Proliferative Diabetic Retinopathy

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaochun Yang ◽  
Jianbiao Xu ◽  
Ruili Wang ◽  
Yan Mei ◽  
Huo Lei ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Controlled Trial ◽  
Control Group ◽  
Intraoperative Bleeding ◽  
Significant Difference ◽  
Pars Plana ◽  
Effective Adjunct

Purpose.To determine the efficacy and safety of preoperative intravitreal conbercept (IVC) injection before vitrectomy for proliferative diabetic retinopathy (PDR).Methods.107 eyes of 88 patients that underwent pars plana vitrectomy (PPV) for active PDR were enrolled. All patients were assigned randomly to either preoperative IVC group or control group. Follow-up examinations were performed for three months after surgery. The primary bioactivity measures were severity of intraoperative bleeding, incidence of early and late recurrent VH, vitreous clear-up time, and best-corrected visual acuity (BCVA) levels. The secondary safety measures included intraocular pressure, endophthalmitis, rubeosis, tractional retinal detachment, and systemic adverse events.Results.The incidence and severity of intraoperative bleeding were significantly lower in IVC group than in the control group. The average vitreous clear-up time of early recurrent VH was significantly shorter in IVC group compared with that in control group. There was no significant difference in vitreous clear-up time of late recurrent VH between the two groups. Patients that received pretreatment of conbercept had much better BCVA at 3 days, 1 week, and 1 month after surgery than control group. Moreover, both patients with improved BCVA were greater in IVC group than in control group at each follow-up.Conclusions.Conbercept pretreatment could be an effective adjunct to vitrectomy in accelerating postoperative vitreous clear-up and acquiring stable visual acuity restoration for PDR.

scholarly journals The effectiveness of preoperative individual information on reducing anxiety and pain after hysterectomy: A randomized controlled trial

2019 ◽  
Vol 10 (1) ◽  
pp. 67
Author(s):  
Hrønn Thorn ◽  
Lisbeth Uhrenfeldt
Keyword(s):  
Randomized Controlled Trial ◽  
Postoperative Pain ◽  
Controlled Trial ◽  
Anxiety Level ◽  
Preoperative Anxiety ◽  
Control Group ◽  
Study Group ◽  
Randomized Controlled ◽  
Significant Difference ◽  
Individual Information

Background and objective: Preoperative anxiety among gynecological patients is well-known and has a direct correlation with postoperative pain. By minimizing preoperative anxiety, the level of postoperative pain may decrease.  The purpose of this study was to evaluate the effect of preoperative structured information and dialogue on patients' anxiety and postoperative pain.Methods: A single-center non-blinded randomized controlled trial. Forty-six women scheduled for hysterectomy were allocated either to the study group or the control group.  The study group was given individual information at a preoperative consultation while the control group was given information at admittance. The main outcome was anxiety level and postoperative pain.Results: Forty participants (study group = 20; control group = 20) were analyzed. No statistically significant difference was found in anxiety level within the first 24 h postoperatively or in postoperative pain within four weeks between the groups.Conclusions: Preoperative individual information and dialogue did not result in significant effects in reducing anxiety level nor did it result in lower postoperative pain score.

A Experimental Study and Clinical Result of Prophylaxis aGVHD with Humanized Anti-CD25 Monoclonal Antibody in Haploidentical BMT.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1251-1251
Author(s):  
Shu-Quan Ji ◽  
Hui-Ren Chen ◽  
Heng-Xiang Wang ◽  
Hong-Min Yan ◽  
Mei Xue ◽  
...  
Keyword(s):  
Median Time ◽  
Conditioning Regimen ◽  
Control Group ◽  
High Dose ◽  
Marrow Graft ◽  
Hla Antigen ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Significant Difference

Abstract Between February 1999 and March 2004, eighty-seven patients with high risk leukemia, age 3–50 (median 19 year), who needed urgent transplant but no HLA-matched or single HLA-antigen mismatched donors available, received unmanipulated HLA haploidentical BMT. The 87 patients were classified as follows AML 27 (CR1 in 7, CR2 in 15 and 5 in relapse), All 38 (CR1 in 4, CR2 in 30 and 4 in relapse) , CML 22 ( 4 in CP, 12 in AP and 6 in BP). All donors were HLA-haploidentical relatives who had at least two major histocompatibility complex antigen mismatched with the recipients. 87 patients underwent haplo-BMT with G-CSF primed BM as stem cells. All patients received a same conditioning regimen including high dose Ara-C, Cyclophosphamide, antithymocyte globulin and total body irradiation to provide both immunosuppression and myeloablation. GVHD prophylaxis consisted of anti-thymocyte globulin, cyclosporin A, methotrexate and mycofenolate mofitel. 72 patients underwent the transplants with the addition of CD25 mAb (Basiliximab Novartis) for GVHD prophylaxis designated as CD25 mAb group. Basiliximab 20mg each by 30min intravenous infusion on 2 hours before transplantion and day 4 after transplantaion. The other 15 patients without Basiliximab for GVHD prophylaxis were as the control group. The two group of patients were comparable in disease status, HLA-disparity and median age of patients. Immunophenotyping, limited dilution assay and colony forming assays were used to measure the effect of Basiliximab on the subsets of lymphocytes, cytotoxic T lymphocyte precursors (CTLp) and hematopoietic cells. All donors were primed with G-CSF at 3-5ug/kg/d for 7 days and the marrow cells were harvested on the eighth day. G-CSF donor priming significantly increased CD34+ and colony forming progenitors in the marrow grafts. More importantly, it significantly reduced lymphocytes and reversed CD4+/CD8+ lymphocyte ratio in the grafts. Both of group who were treated with and without Basiliximab had similar marrow graft contents. All patients established trilineage engraftments.The median time to achieve an absolute neutrophil count 0.5x109/L was 19 days (range, 13 to 24 days). The median time to achieve platelets above 20x109/L was 22 days (range, 16 to 32 days). Between the two groups were no differences in engraftment. Incidence of grades II–IV acute GVHD were 13.9% with GVHD-related deaths 6.9% in Basiliximab group and 33.3% with 20% GVHD-related deaths in control group. There were a significant difference between the anti-CD25 mAb treated Vs non-treated group.Forty-nine patients who survived over 12 months were eligible for the evaluation of cGVHD. 12 patients developed extensive cGVHD, one in control group and eleven in Basiliximab group. 49 were alive in CR during a median follow-up of 30 months (range3–64 months), 42 in Basiliximab group and 7 in control group. Basiliximab significantly decreased alloreactive CTLp by 10–100 fold in limiting dilution assays. It had no effect on hematopoietic stem and progenitor cells as determined by in vitro colony-forming assays.The addition of basiliximab as aGVHD prophylaxis effectively reduced severe lethal aGVHD in haplo-BMT. It is possible to selectively eliminate or reduce the number of alloreactive T cells with anti CD25 antibody, which results in prevention of or a reduction in the severity of GVHD.

Effect of Rituximab on the Incidence of GVHD in Lymphoma Patients who Received the BEAM-Conditioning and an Allogeneic Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4980-4980
Author(s):  
Issa F. Khouri ◽  
Rima M. Saliba ◽  
Daniel R. Couriel ◽  
Grace-Julia Okoroji ◽  
Sandra Acholonu ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cells ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Control Group ◽  
Study Group

Abstract It has been postulated that B cells functioning as antigen-presenting cells may have an important role in the pathogenesis of GVHD. Depletion of donor cells from B-cells resulted in a low incidence of GVHD in mouse model (Schultz et al. BMT1995:16:289–289). More recently, we observed a lower incidence of chronic (and to a lesser extent acute GVHD) in patients with CLL who received an allogeneic stem cell transplantation after a non-myeloablative conditioning regimen containing rituximab (Exp Hematol32:28–35, 2004). The purpose of this study is to investigate the effect of rituximab on GVHD in the setting of a more intense chemotherapy with BEAM, in patients who received an allogeneic peripheral blood stem cell from HLA-identical siblings. To test this hypothesis, we retrospectively studied 11 consecutive patients with non-Hodgkin’s lymphoma who received BEAM/Rituximab at the M. D. Anderson Cancer Center. We attempted to match these patients by age, donor-recipient gender, and donor-recipient CMV reactivity to a historical control of 44 patients with lymphoma, who received BEAM alone as a conditioning regimen, without the Rituximab. Tacrolimus and methotrexate were used for GVHD prophylaxis in both groups. A total of 10 patients in the study group, could be matched with 19 patients in the control group and were included in the final analysis. The outcome of the 2 groups is shown below: Rituximab-Study Group Control Group -value P No. of patients 10 19 Median age 41 44 0.4     (range) (19–55) (19–60) Patient-Donor sex-matched 9(82%) 18(95%) 0.6 Median # CD34 + cells infused (106/kg) 5.1 4.73 0.1 Patient or Donor CMV+ 9(82%) 18(95%) 0.6 Patient and Donor CMV − 1(10%) 1(5%) Median # prior chemoregimens 3 3 0.9     range (1–8) (1–9) Median follow-up 17 38     range (8–48) (27–77) Acute GVHD 2–4 (n,%) 5(50%) 7(37%) 0.5 Acute GVHD 3–4 (n,%) 3(30%) 5(26%) 0.6 Chronic GVHD (n, % cumulative incidence) 8 (90% + 15) 10 (53% + 12 0.01 Our data suggest that the described protective effect of Rituximab against GVHD in mouse models or in the setting of non-myeloablative allogeneic transplantation, may be overcome by the BEAM. This more intense conditioning regimen may induce more GVHD by enhancing T-cell cytokines release and by causing more gastrointestinal toxicity, thus allowing for a greater antigen presentation.

Long-Term Follow-Up of a Randomized Phase III Multicenter Study Comparing a Standard Versus an Intensified Conditioning Regimen for High-Dose Chemotherapy in Patients with Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 945-945
Author(s):  
Roland Fenk ◽  
Peter Schneider ◽  
Martin Kropff ◽  
Ali-Nuri Huenerlituerkoglu ◽  
Ulrich Steidl ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Conditioning Regimen ◽  
High Dose Chemotherapy ◽  
Phase Iii ◽  
Study Endpoint ◽  
Primary Study ◽  
High Dose ◽  
Significant Difference

Abstract High-dose chemotherapy (HDT) improves the outcome of patients with multiple myeloma (MM) in comparison to conventional chemotherapy. Dose-escalating strategies including tandem HDT are currently evaluated to further improve remission rates and survival of patients. Therefore we conducted a randomized multicenter trial to compare an intensified conditioning regimen with the current standard high-dose melphalan. The primary study endpoint was response rate, with overall survival (OS), event-free survival (EFS) and toxicity analysed as secondary endpoints. Between 1997 and 1999 a total of 56 patients with stage II and III disease, who were matched for age (median 56 years), number of previous therapies (median time from diagnosis to transplant 7 months) and different risk factors (beta2-microglobulin, LDH, CRP, cytogentic abnormalities, chemoresistant disease, IgA-subtype, renal impairment), were randomized. All patients received 2 courses of oral idarubicine/dexamethasone and 2 courses of intravenous cyclophosphamide/adriamycine in combination with G-CSF followed by peripheral stem cell collection. Thirty patients were treated with melphalan 200mg/m2 (HD-M) whereas 26 patients received idarubicine 42mg/m2, melphalan 200mg/m2 and cyclophosphamide 120mg/kg (HD-IMC) followed by autologous blood stem cell transplantation. Acute toxicity was higher with HD-IMC, including 5 (20%) treatment-related deaths due to infections versus none (0%) in the HD-M group. This lead to early termination of the study. Severity of mucositis (grade III-IV 19 vs. 8 pts., p=0.001), CRP (20 vs. 7 mg/dl, p<0.001), days of fever (11 vs. 3, p<0.001), days with iv-antibiotics (13 vs. 4, p<0.001), number of erythrocyte-transfusions (6 vs. 2, p<0.001), number of platelet-transfusions (16 vs. 4, p<0.001) and days to granulocyte engraftment (18 vs. 11, p=0.007) were significantly higher after HD-IMC. After a follow-up of 5 years analysis restricted to patients surviving the first 30 days after HDT showed a trend to higher response rates (CR+vgPR: 47% (95%CI 24–72%) vs. 35% (95%CI 18–56%), PR 37% (95%CI 17–63%) vs. 48% (95%CI 29–68%) and time-to-progression (median 31 vs. 15 months, p=0.1) in the HD-IMC treatment arm in comparison to HD-M, but there was no significant difference in EFS and OS (median 22 vs. 30, p= 0.31 and 66 vs. 66 months, p=0.8, respectively). Univariate analysis demonstrated that LDH levels > 200 U/L (p=0.04) and chemoresistant disease (p=0.05) were a bad prognostic factor for EFS. Beta2-Microglobulin levels > 5mg/dl (p=0.01), abnormal conventional cytogenetics (p=0.02) and LDH levels > 200 U/L (p=0.03) were predictive for an inferior OS. In conclusion intensified conditioning for HDT had an intolerable high treatment-related mortality and did not improve EFS and OS in patients with multiple myeloma.

The Utility of Consolidative Upfront High Dose Chemoradiotherapy and ASCT in Patients with Mantle Cell Lymphoma (MCL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2072-2072
Author(s):  
Daniel Persky ◽  
Carol S. Portlock ◽  
Simone Lessac-Chenen ◽  
Alexia Iasonos ◽  
Andrew D. Zelenetz ◽  
...  
Keyword(s):  
Bone Marrow Involvement ◽  
Conditioning Regimen ◽  
Stage Iv ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Significant Difference ◽  
Dose Dense

Abstract Introduction: Two approaches to improve progression-free survival (PFS) in MCL are intensifying induction, as with hyperCVAD/M-A regimen, or intensifying consolidation with high dose chemoradiotherapy (HDT) and ASCT as in the prospective European MCL Network Trial. At MSKCC the strategy is to incorporate both approaches by administering an anthracycline-containing regimen in a dose dense fashion (CHOP- or R-CHOP-14) followed by consolidation with ICE (ifosfamide, carboplatin, etoposide) and HDT/ASCT. Patients: Forty six patients with newly diagnosed MCL underwent HDT/ASCT between 11/96 and 2/05. The median age was 55 years; 74% were male; 72% had bone marrow involvement, 39% had GI involvement, 7% were in leukemic phase, and 91% presented with stage IV disease. Splenomegaly was seen in 35%, B symptoms in 9%, KPS>70 in 93%, elevated LDH in 23%, and blastoid histology in 9%. Results: Induction was 4 to 6 cycles of CHOP-14 (43%), R-CHOP-14 (37%), or other doxorubicin-containing regimen (20%). Consolidation was performed with 2–3 cycles of ICE in 53% or R-ICE in 39%. Upfront treatment was well tolerated and permitted adequate stem cell collection and prompt transition to HDT/ASCT. Conditioning regimens were TBI/CY/VP-16 (59%) and BEAM (41%). Involved field radiation therapy was administered to 65%. Post-ASCT rituximab maintenance was given to 39%, with 57% of patients receiving rituximab as part of their treatment. Anthracycline-based induction led to CRu of 44% and ORR of 98%. Seventy two percent of patients were transplanted in CR, while the remaining 28% were in PR. At a median follow-up of 2.5 years (range 0.4–8.0 years) 17% of the patients have died and 24% have had progressive disease. The median OS and PFS have not been reached (lower 95% CI, 5.7 years and 4.4 years, respectively). The 5-year PFS and OS are 58% and 83%, respectively. The use of rituximab at any point during treatment prolonged PFS - only 1 of 26 patients receiving rituximab relapsed, as compared to 10 of 20 patients who were rituximab naive (p=0.03); thus far there is no significant difference in OS. There was no day 100 treatment related mortality. One patient developed bronchiolitis obliterans after ASCT and died of pulmonary fibrosis 6.5 years later; 3 patients have died of secondary cancers - one case each of MDS (1.6 years after ASCT), melanoma and lung cancer. Conclusion: These data provide evidence that dose-dense induction with CHOP-14 or R-CHOP-14 and consolidation with ICE/HDT/ASCT appears to be safe and effective, with minimal acute toxicity. Although the median follow-up is short, the use of rituximab appears to improve PFS. This contrasts with the findings of German LGLSG and may be a consequence of in vivo rituximab purging. Future therapy could incorporate all the successful elements of prior treatment programs, including R-CHOP-14, R-ICE, and radioimmunotherapy with high dose chemotherapy conditioning regimen, followed by ASCT and rituximab-based maintenance. PFS stratified by Rituximab PFS stratified by Rituximab

Reduced Intensity Conditioning (RIC) with Cladribine, Busulfan and 4 Gy Total Body Irradiation (TBI) for Bone Marrow Transplantation (BMT) from an HLA-Matched Unrelated Donor (URD): A Prospective Multi-Institutional Clinical Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5397-5397 ◽  
Author(s):  
Sung-Won Kim ◽  
Masayuki Hino ◽  
Kazuo Hatanaka ◽  
Yasunori Ueda ◽  
Ryuji Tanosaki ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Survival Rates ◽  
Conditioning Regimen ◽  
High Response Rate ◽  
High Dose ◽  
Unrelated Donor ◽  
Grade Ii ◽  
Neutrophil Engraftment

Abstract [Background] We report the results of a prospective multi-institutional clinical trial of BMT from an HLA-matched URD following RIC. [Patients and Methods] The conditioning regimen included cladribine 0.11 mg/kg on day -8 to day -3, busulfan 4 mg/kg po on day -6 and day -5, and 4 Gy TBI on day -1. GVHD prophylaxis included cyclosporine and short-term methotrexate. Patients with hematologic diseases were eligible for this study if they were either older than 50 years or had significant medical contraindications to undergo conventional transplantation. Primary endpoints were neutrophil engraftment and achievement of complete donor-type chimerism (CD3+ cells >90%) on day 90. Regimen-related toxicities (RRT) between day -8 and day 28 were assessed by the NCI-CTC v2.0. A total of 27 patients were registered, but one patient was removed before transplant because of severe fungal infection. [Results] The median follow-up time was 722 days (range, 324–996) among survivors. The median age of patients was 56.5 years (36–64). Nine of the 26 patients (36%) had advanced-stage diseases and 3 (11%) had failed previous high-dose autologous or allogeneic transplantation. The diagnoses included AML (n=9), MDS/MPD (n=7), NHL (n=3), ALL (n=2), CML, ATLL, PCL, biphenotypic acute leukemia, and severe aplastic anemia (n=1). The median number of infused nucleated cells was 2.2 × 108/kg. After transplant, while one patient experienced engraftment failure and subsequent sepsis, and died on day 34, the remaining 25 patients achieved neutrophil engraftment (median, 17th day). Another patient was censored from the study due to grade 4 liver dysfunction, which developed on day 19, which left 24 patients for the chimerism analysis. The percentage of donor chimerism in CD3+ cells on days 28, 56 and 90 was, respectively, 88% (21/24), 100% (24/24) and 100% (24/24). Grade 3 RRT included arrhythmia (n=1), hypoxia (n=3), hyperbilirubinemia or hypertransaminasemia (n=7), stomatitis (n=18) and diarrhea (n=4), and grade 4 RRT included hypoxia (n=1) and hyperbilirubinemia (n=1). Acute GVHD of grade II, III and IV occurred in 27%, 27% and 4%, respectively. Ten of 15 evaluable patients (67%) had extensive chronic GVHD. CMV reactivation occurred in 23 patients (89%); 4 had histologically confirmed CMV colitis, 1 had CMV pneumonitis and 1 had CMV hepatitis, while the remaining patients had asymptomatic viremia. Of the 16 patients with measurable disease at the time of BMT, 15 achieved complete remission. The 100-day and 1-year cumulative incidences of non-relapse mortality (NRM) estimated by the Kaplan-Meier method were 20% and 54%, respectively. The cause of death that contributed to NRM was infection, with grade 0–I acute GVHD in 29% and grade II–IV acute GVHD in 71%. The 100-day and 1-year cumulative incidences of relapse were 8% and 35%, respectively, and the 1-year overall and progression-free survival rates were 42% and 30%, respectively. [Conclusions] The results support the feasibility of this procedure with a high response rate, but there is still a problem with the high NRM due to uncontrollable infections primarily associated with GVHD.

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