High Dose (HD-AraC) vs Standard Dose Cytosine Arabinoside (SD-AraC) during Induction in Acute Myelogenous Leukemia (AML): Impact on Stem Cell Mobilization after Consolidation and on Autologous Transplantation (Second Report of the EORTC-Leukemia Group (LG) - GIMEMA AML-12 Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 609-609
Author(s):  
Roelof Willemze ◽  
Stefan Suciu ◽  
Franco Mandelli ◽  
T.M. de Witte ◽  
Boris Labar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Standard Dose ◽  
Autologous Transplantation ◽  
Early Death ◽  
Myelogenous Leukemia ◽  
Phase Iii ◽  
High Dose ◽  
No Donor ◽  
Platelet Recovery ◽  
Poor Risk

Abstract The AML-12 randomized phase III trial of EORTC-LG and GIMEMA assessed the efficacy and toxicity of HD-AraC (3 g/m2/12 hrs for 4 days) with daunorubicin (50 mg/sqm for 3 days) and etoposide (50 mg/sqm for 5 days) vs SD-AraC (100 mg/sqm for 10 days) with the same drugs. Patients (pts) in complete remission (CR) received consolidation (Co) consisting of AraC (500 mg/sqm/12 hrs for 6 days) and daunorubicin. Subsequently an allogeneic (allo-SCT) or autologous stem cell transplantation (auto-SCT) was planned according to donor availability and age. A 2nd randomization was performed after Co in pts without a donor: auto-SCT followed or not by low dose IL-2. From 9 1999 till 7 2006, 1675 AML pts (APL excluded), age <61 years, from 67 centers (23 EORTC-LG and 44 GIMEMA) entered. Currently 1571 pts have been randomized for induction and 429 pts post-Co. During the induction toxicity was similar in the 2 arms except for conjunctivitis: 6% (HD-AraC) vs 0% (SD-AraC). HD-AraC given in the induction had no impact on the organ toxicity during Co but platelet recovery (> 50x109/l) was longer (median 4.0 vs 3.3 weeks; P=0.01). Among 886 pts randomized until 7 2005 by EORTC centers and 6 large GIMEMA centers, median follow-up of 2.5 years, 815 were evaluable for response. Out of 643 pts who reached CR, 57 went off study (toxicity, early progression). Among the remaining 586 who received Co, 37 could not be evaluated (early death/relapse, too early) and 549 were still CR after Co: 297 pts had no donor/no sibling, 197 had a donor and 55 were not typed. In these 3 groups the present estimates of the SCT rates are: 63% (auto-SCT), 71% (allo-SCT) and 69% (auto-SCT), resp. The 2.5-yr DFS rates (SE%) were 45% (3%), 61% (4%), and 67% (7%), resp. In pts < 50 yrs, 216 pts had no donor/no sibling, 135 had a donor and 14 have not been typed. For the first 2 groups, the 2.5 yr DFS rates (SE%) were 50% (4%) vs 68% (4.5%), hazard ratio=0.64, 95% CI (0.44, 0.93), P=0.02. In pts without a donor/a sibling successful mobilization of blood stem cells (b-SC) after Co was in HD-Ara-C vs SD-Ara-C arm 53 vs 69%, of failure/postponement 37 vs 24%, and other 9.5 vs 7%. The rate of auto-SCT was similar (65 vs 64%), but harvest of BM cells was more often required in the HD-AraC group (15 vs 4.5%). Pts with an insufficient/delayed b-SC harvest had a longer (P<0.001) platelet recovery (> 50x109/l) after Co than those with a successful harvest: median = 6.7 vs 3.3 wks. Among 393 pts with information on cytogenetics, 14% had good risk, 50% normal, 23% other and 13% poor risk (-5/5q-, -7/7q-, complex). The 2.5-year EFS (no CR, time to relapse or death in CR) rates (SE%) were 68% (7%), 42% (4%), 32% (5%) and 14% (5%), resp. So far: toxicity of HD-Ara-C was acceptable; in those who received HD-AraC in induction platelet recovery after Co was longer and the rate of successful b-SC collection was lower; SCT rates are high and similar in the 2 randomized arms; pts <50 yrs with a donor do have a longer DFS; pts with poor risk cytogenetics continue to have a poor prognosis.

High Dose Cytosine Arabinoside (HD-AraC) vs Standard Dose AraC (SD-AraC) during Induction, and Stem Cell Transplantation Followed by IL-2 or No Maintenance in Acute Myelogenous Leukemia (AML): First Report on the AML-12 Phase III Trial of the EORTC-Leukemia Group (LG) and GIMEMA.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 271-271 ◽  
Author(s):  
Roelof Willemze ◽  
Stefan Suciu ◽  
Franco Mandelli ◽  
Theo de Witte ◽  
Boris Labar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myelogenous Leukemia ◽  
Phase Iii ◽  
High Dose ◽  
Platelet Recovery ◽  
Phase Iii Trial ◽  
Poor Risk ◽  
Grade 3

Abstract The AML-12 randomized phase III trial of EORTC-LG and GIMEMA assessed the efficacy and toxicity of HD-AraC (3 g/m2 q 12 hrs for 4 days) in combination with daunorubicin (50 mg/m2 for 3 days) and etoposide (50 mg/m2 for 5 days) vs SD-AraC (100 mg/m2 for 10 days) combined with the same drugs. All patients (pts) who reached complete remission (CR) received one consolidation course consisting of ID-AraC (500 mg/m2 q 12 hrs for 6 days) and daunorubicin. Subsequently an allogeneic (allo-SCT) or an autologous stem cell transplantation (auto-SCT) was planned according to donor availability and age. A second randomization was performed after consolidation in pts without a donor: auto-SCT followed or not by maintenance with low dose IL-2 (4–8 x 106 IU s.c. for 5 days per month) during one year. From 1999 till July 2005, 1359 AML pts (APL excluded), age < 61 years, from 65 centers (23 EORTC-LG and 42 GIMEMA) entered the trial. Currently 1235 pts have been randomized for induction and 355 pts post-consolidation. During the induction course toxicity profiles were similar in the 2 arms; however in the HD-AraC group the incidence of grade 3–4 liver transaminase abnormalities (9% vs 5%) and conjunctivitis (16% vs 1%) was higher, and time to neutrophil and platelet recovery shorter. HD-AraC in the induction cycle had no impact on the organ toxicity during the consolidation course, but the platelet recovery (> 50 x 109/l) was significantly longer (median 4.4 vs 3.1 weeks). The IL-2 schedule was well tolerated in most pts with fatigue (20%), rigor/chills (6.5%), arthralgia/myalgia (4%) as the main grade 3–4 toxicities. Among 613 pts randomized until July 2004 by EORTC centers and 6 large GIMEMA centers, with a median follow-up of 2.2 years, 465 reached CR. Among 428 pts who received a consolidation course, 67 have a CR status still “too early” and 361 were still CR after consolidation: 156 had no donor, 136 had a donor and 69 were too old to be HLA typed. In these 3 groups the present estimates of the transplantation rates are: 60% (auto-SCT), 74% (allo-SCT) and 65% (auto-SCT), respectively. The 2-yr DFS rates (SE%) were 51.8% (4.4%), 66.5% (4.3%), and 52.3% (6.7%), respectively. Among 337 pts with information on cytogenetics, 41 (13%) had good risk, 167 (53%) normal, 70 (22%) other and 39 (12%) poor risk cytogenetics (−5/5q-, −7/7q-, complex). The 2-year EFS (time to no CR, relapse, death) rates (SE%) were 74.2% (5.7%), 43.7% (4.1%), 36.3% (6.2%) and 17.4% (7.1%), respectively. So far: the toxicity of HD-Ara-C is acceptable in induction of de novo AML pts < 61 years old, but better prevention of conjunctivitis should be stressed; platelet recovery after consolidation is longer in those who received HD-Ara-C in induction; transplantation rates are high after consolidation; IL-2 toxicity is acceptable; pts with a donor have a better outcome, those with good/poor risk cytogenetics have an excellent/poor outcome, respectively.

Phase III Randomized Stem Cell Mobilization Trial Comparing Standard Vs Double-Dose G-CSF Vs Standard Doses of G-CSF Plus GM-CSF in Hard to Mobilize Patients Undergoing An Autologous Hematopoietic Stem Cell Transplant (HSCT).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3228-3228
Author(s):  
Elizabeth Berger ◽  
Christopher Seet ◽  
Mala Parthasarathy ◽  
Tulio Rodriguez ◽  
Scott E. Smith ◽  
...  
Keyword(s):  
Stem Cell ◽  
Standard Dose ◽  
Stem Cell Mobilization ◽  
Phase Iii ◽  
Control Group ◽  
High Dose ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Cell Mobilization

Abstract Abstract 3228 Poster Board III-165 Introduction Using standard dose G-CSF (10 μg/kg) for stem cell mobilization, 25-40% of patients, deemed to be hard to mobilize based on prior therapy, will not collect sufficient HSC (> 2-2.5 × 106 CD34/kg) to proceed to a prompt autotransplant. Strategies to improve CD34/kg yields have included dose escalating G-CSF up to 30 μg/kg or combining G-CSF and GM-CSF. While dose escalated G-CSF is effective in increasing CD34 yields in normal donors as is the combination of G-CSF and GM-CSF, their comparative value in pre-treated patients has not been tested. To determine the value of these strategies, we performed a randomized comparison of high dose G-CSF (30 μg/kg as 2 doses 12 hours apart), to the combination of simultaneous single daily doses of G-CSF (10 μg/kg) plus GM-CSF (5 μg/kg), to a control group receiving G-CSF at an equivalent total dose of cytokine to the combination arm (15μg/kg) as a single dose. Patients and Methods Patients were eligible if heavily pre-treated, defined as: a minimum of 10 total cycles of combination chemotherapy and two prior regimens, or a total of 6 chemotherapy cycles if the patient also received RT to marrow bearing sites, platinum-based chemotherapy or 2 or more cycles of any BCNU or fludarabine containing regimen. Baseline WBC had to be > 3000/μl, ANC > 1500/μl and a platelets > 100,000/μl. Twelve liter aphereses began on day 5 of mobilization, and continued until ≥ 4 × 106 CD34/kg were collected or a maximum of 5 aphereses. Patients typically proceeded to transplant if they had ≥ 2.5 × 106 CD34/kg collected and were always re-mobilized if they collected < 2.0 × 106 CD34/kg. CD34 subsets (CD34+/CD33- and CD34+/CD38-) were also assessed for the 3 groups to determine if more primitive HSC were mobilized by the 2 novel strategies. The sample size was calculated based as follows: 60% of the control group would collect 2.5 × 106 CD34/kg and this would rise to 90% in one or both study arms. The detection of such differences with a power of 80% and a 2-sided alpha level of 0.025 required a total sample of 120 patients. Results A total of 120 patients were randomized; 119 were eligible. Patient demographics, shown in the Table, were matched among the three groups: The % of patients collecting ≥2.5 × 106 CD34/kg was: standard G: 60%, high dose G: 57% (p = 1.0), G + GM: 41% (p = 0.1). Median CD34 collected in first mobilization were, 3.6 × 106/kg, 3.0 × 106/kg (p = 0.22) and 2.0 × 106/kg (p = 0.05) respectively in a median of 4, 4, and 5 aphereses (p = NS). Re-mobilization rates: standard G; 37.5%, high dose G: 35%; G + GM: 50% (p = NS). Total median CD34 collected from first and any second mobilizations were: standard G: 4.8 × 106/kg, high dose G: 3.9 × 106/kg, and G + GM: 3.5 × 106/kg. One patient in the standard G arm and 3 in high dose G did not proceed to transplant due to poor initial mobilization and progression in 2, and one each for progression or poor mobilization alone. There were no significant differences in median engraftment times: for ANC, 10, 11 and 15 days respectively for the standard G-, high dose G- and G + GM arms and for platelets, 11, 13 and 14 days respectively. The overall survivals @ the median f/u time of 37 months were 59.8%, 61.8% and 48.1% respectively (p = 0.272) for the three groups. The % primitive HSC (CD34+/CD33- and CD34+/CD38-) from the first mobilization were identical in the 3 patient groups. Conclusions We found no advantage to dose escalated G-CSF nor to the combination of G-CSF and GM-CSF to mobilize HSC for autotransplantation in heavily pre-treated patients. We also did not find higher numbers of more primitive CD34 subsets mobilized by these newer strategies. Alternative approaches, e.g. the combination of plerixifor + standard dose G-CSF (Stiff et al: BBMT; 15:249-56, 2009) would appear to be the preferred method of initial HSC mobilization for heavily pre-treated patients. Disclosures Stiff: Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

High Dose (HD-AraC) Vs Standard Dose Cytosine Arabinoside (SD-AraC) During Induction and IL-2 Vs Observation After Consolidation/Autologous Stem Cell Transplantation in Patients with Acute Myelogenous Leukemia (AML): Final Report of the AML-12 Trial of EORTC and GIMEMA Leukemia Groups on the Value of High Dose AraC

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 257-257 ◽  
Author(s):  
Roelof Willemze ◽  
Stefan Suciu ◽  
Franco Mandelli ◽  
Giovanna Meloni ◽  
Boris Labar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Myelogenous Leukemia ◽  
Phase Iii ◽  
High Dose ◽  
Treatment Difference

Abstract Abstract 257 The AML-12 randomized phase III trial of EORTC-LG and GIMEMA assessed the efficacy and toxicity of HD-AraC (3 g/sqm/12 hrs for 4 days) combined with daunorubicin (50 mg/sqm/d for 3 days) and etoposide (50 mg/sqm/d for 5 days) vs SD-AraC (100 mg/sqm/d for 10 days) with the same drugs, in previously untreated AML < 61 year old patients (APL excluded). Patients (pts) in complete remission (CR) had to receive consolidation consisting of AraC (500 mg/sqm/12 hrs for 6 days) and daunorubicin. Subsequently an allogeneic (allo-SCT) or autologous stem cell transplantation (auto-SCT) was planned according to donor availability and age. A 2nd randomization had to be done after evaluation of consolidation in pts without a donor: auto-SCT followed or not by low dose IL-2. The aim of the trial was to detect an 8% treatment difference (from 35% to 43%) in the 5-yr overall survival (OS) rate, corresponding to a hazard ratio (HR) of 0.80 (alpha=5%, power=95%); secondary endpoints were response to induction, toxicity, disease-free survival (DFS) from CR. Randomization was performed centrally; the 1st randomization was stratified for age (<46 vs > 45 yrs), performance status, WBC and center. Intent-to-treat analysis was done. From 9/1999 till 1/2008, 2005 pts from 68 centers were randomized. Due to insufficient reporting, 3 centers, who recruited 63 patients, have been excluded from the analysis. The remaining 1942 pts (872 pts entered by EORTC-LG and 1070 by GIMEMA) 969 were randomized in SD-AraC and 973 in HD-AraC arm; among them 25 and 28, respectively, were ineligible, but kept in the analysis. Both arms were comparable with respect to gender, age (median=45 yrs), disease history, initial leukocyte count, PS, FAB and cytogenetics. At a median follow up of 6 yrs, 1114 pts had died. Results: After 1 or 2 courses of induction, CR was achieved in 1430 pts (73.6%); 684 (71.9%) pts (SD-AraC group) vrs 746 (78.7%) pts (HD-AraC group): p=0.002. Resistance was documented in 173 (18.2%) vrs 123 (13%), and death during induction in 85 (8.9%) vrs 71 (7.5%) pts, respectively. Induction toxicity profile and grade was similar in the 2 arms except for conjunctivitis grade 3: HD-AraC>SD-AraC. CR rates for pts<46 yrs were 74.7% (SD-AraC) and 81.4% (HD-AraC) and for pts>45 yrs 66.4% (SD-AraC) and 71.8% (HD-AraC). 634 pts (SD-AraC and 686 (HD-AraC) received a consolidation cycle. Among 765 CR-pts<46 yrs 284 pts had an HLA identical sibling (<46D) and 481 did not or had not been typed (<46NoD). Among 665 CR-pts>45 yrs 225 pts had an HLA identical sibling (>45D) and 440 did not or had not been typed (>45NoD). In the <46D group 211 underwent an allo-SCT and 11 an auto-SCT. In the <46NoD group 274 underwent an auto-SCT and 29 a MUD-SCT; in the >45D group 147 underwent an allo-SCT and 14 an auto-SCT. In the >45NoD group 244 underwent an auto-SCT and 12 a MUD-SCT. Comparisons of treatments arm regarding OS from randomization, DFS and Survival (S) from CR are indicated in the Table. The impact of age on the treatment difference regarding OS was almost significant (p=0.06). In pts >45 who reached CR, the decrease in the relapse rate in the HD-Ara-C arm vrs SD-Ara-C arm (45.5% vs 49.4%) was counterbalanced by an increase in the death in CR rate (18.4% vs 13.2%). Conclusion: The final evaluation of the EORTC-GIMEMA AML-12 trial shows that, with a median follow-up of 6 years, HD-AraC in the induction treatment leads to a significantly higher CR rate than SD-Ara-C and results in improvement in overall survival but only in pts under the age of 46 years. Disclosures: Muus: Amgen: Membership on an entity's Board of Directors or advisory committees. Beksac:Janssen Cilag: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau.

Autologous Hematopoietic Stem Cell Collection and Transplantation in Acute Myeloid Leukemia Patients in Second Remission after Treatment with Fractionated Gentuzumab Ozogamycin.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5211-5211
Author(s):  
Delphine Rea ◽  
Emmanuel Raffoux ◽  
Anne Laure Taksin ◽  
Adrienne De Labarthe ◽  
Nicolas Boissel ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Myeloid Leukemia ◽  
Autologous Transplantation ◽  
Normal Karyotype ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Platelet Recovery ◽  
Acute Myeloid

Abstract Gemtuzumab ozogamicin (GO) at fractionated doses of 3 mg/m2 on days 1, 4 and 7 has recently shown efficacy with minimal liver toxicity and without veino occlusive disease (VOD) in patients with acute myeloid leukemia (AML) in first relapse. We report on autologous hematopoietic stem cell (HSC) collection and transplantation in 4 AML patients (median age 61; 54–64) in 2nd remission (CR2) after fractionated GO treatment uneligible for allogeneic HSC transplantation. Peripheral blood (PB)-HSC were collected by leukapheresis after mobilization with amsacrine + AraC (patients 1–3) or high dose AraC (patient 4) and subsequent G-CSF at 5 microgr/kg/day. In patient 1 (AML2 normal karyotype Flt3 wt), PB-HSC collection started at day 22 post-chemotherapy (CT) with a CD34 count of 13.4/microl and 2 cytapheresis were required to yield a total of 11.8×108 nucleated cells (NC)/kg, 3.7×106 CD34/kg and 6.9×104 CFU-GM/kg. In patient 2 (AML4, normal karyotype, Flt3 ITD), PB-HSC collection started at day 20 post-CT with a CD34 count of 8.2/microl and 3 cytapheresis were required to yield a total of 14.8×108 NC/kg, 3.1×106 CD34/kg and 33.7×104 CFU-GM/kg. In patient 3 (AML2 normal karyotype, Flt3 ITD), PB-HSC collection started at day 20 post-CT with a CD34 count of 30.2/microl and 2 cytapheresis were required to yield a total of 5.3×108 NC/kg, 6×106 CD34/kg and 42.5×104 CFU-GM/kg. PB-HSC from patient 3 were purged in vitro with mafosfamide, yielding final CN, CD34 and GM-CFU doses of respectively 4.9×108/kg, 5.2×106/kg and 0×104/kg. In patient 4 (AML1 normal karyotype, Flt3 wt), bone marrow (BM)-HSC were harvested and purged with mafosfamide. Prior purging, CN, CD34 and GM-CFU doses were respectively 1.7×108/kg, 6.7×106/kg and 16.1×104/kg. After purging, CN, CD34 and GM-CFU doses were respectively 0.36×108/kg, 3.6×106/kg and 0.1×104/kg. In patient 4, PB-HSC collection for rescue started at day 16 post-CT with a CD34 count of 27.4/microl and 1 cytapheresis was sufficient to yield a total of 1.8×108 NC/kg, 3.4×106 CD34/kg and 36.7×104 CFU-GM/kg. Autologous HSCT was performed after conditionning with busulfan and cyclophosphamide. Autologous grafts consisted in unpurged PB-HSC in patient 1 and 2, purged PB-HSC in patient 3 and purged BM-HSC in patient 4. All patients received continuous heparin infusion at 100U/kg/day as VOD prophylaxis. Extra hematological adverse events comprised grade 3–4 oral mucitis, grade 2–3 nausea and vomiting (n=4), grade 2–3 diarrhea (n=3), grade 1 liver enzyme elevation (n=4) and grade 1–3 cholestasis. Three patients presented fever of unknown origin, one showed gram-negative systemic infection and one showed clostridium difficile-associated diarrhea. No VOD was observed. Neutrophil recovery above 0.5/L occurred between day 25 and day 40. Platelet recovery above 20/L occurred at day 18 and day 300 in patients 2 and 4, and never occurred in patients 1 and 2. These latter relapsed 3 months after transplantation. Patients 3 and 4 are still in CR2, 7 and 21 months after transplantation. PB and BM collection after fractionated GO treatments for AML is feasible. After autologous transplantation, no VOD is observed but platelet recovery is severely impaired.

Autologous (Auto) Peripheral Blood Stem Cell (SCT) As a Consolidation Therapy for Patients with Acute Myeloid Leukemia (AML) in 1st Complete Remission (CR): A Single Institution Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4505-4505
Author(s):  
Amanpreet Buttar ◽  
Deepa Jagadeesh ◽  
Jan Cerny ◽  
Muthalagu Ramanathan ◽  
Zheng Zhou ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Time ◽  
Conflicts Of Interest ◽  
Standard Dose ◽  
Medical Center ◽  
Progression Free Survival ◽  
High Dose ◽  
Consolidation Therapy ◽  
Platelet Recovery ◽  
Entire Cohort

Abstract Abstract 4505 Introduction: Patients with AML in 1st CR are frequently consolidated with an auto SCT but the role of this modality in the management of AML is still not fully defined. Methods: Retrospective analysis was performed on all patients who underwent an auto SCT for AML in 1st CR at UMass Memorial Medical Center from January 2000 to December 2010. Data was analyzed as of August 2011. The study was approved by UMass Memorial Medical Center IRB. Results: 25 Patients were identified from the database. There were 13 males and 12 females. The median age was 46 years range (19–72). Cytogenetics was good risk in 6 patients, intermediate risk in 14, poor risk in 3 and unknown in 2 patients. Induction chemotherapy was standard dose Ara-C based in 13 patients and high dose Ara-C based regimen in 12 patients. Median time from diagnosis to transplant was 133 days range (107–362). Stem cell mobilization regimen consisted of Ara-C/Etoposide (E) in 21 (80%), Cyclophosphamide (Cy) in 3 (12%) and Mitoxantrone/Ara-C/E in 1 (4%). Preparative regimen included Busulfan (Bu) 4/ E in 17 (68%), Bu4/Cy in 5 (20%) and high dose Melphalan in 3 (12%). A median of 4.56 ×106 range (1.05 × 106 – 9.67 × 106 ) CD34 cells/kg were infused. 3 patients failed to engraft. Median time to neutrophil recovery was 11 days range (9 to 16) and platelet recovery was 20 days range (9 to 116). 100 day mortality was 12% (3/25). Median follow of the entire cohort is 6.5 years range (0.6 – 10.7). Total of 9 patients died. The cause of death included disease in 7, sepsis in 1 and unknown in 1 patient. Kaplan Meier estimate for progression free survival (PFS) and overall survival (OS) was 72% and 80% at 6 months and 62% and 61% at 3 years. Conclusion: ASCT is an effective and safe intensive consolidation therapy for patients with AML in 1st CR. Disclosures: No relevant conflicts of interest to declare.

Peripheral Blood Stem Cell Mobilization by G-CSF Alone and Engraftment Kinetics Following Autologous Transplantation in Children and Adolescents with Solid Tumor.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5197-5197
Author(s):  
Hiroyoshi Watanabe ◽  
Tsutomu Watanabe ◽  
Hiroko Suzuya ◽  
Yoshifumi Wakata ◽  
Toshihiro Onishi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Autologous Transplantation ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Platelet Recovery ◽  
Irradiation Group ◽  
Cd34 Cells ◽  
Pediatric Cancer Patients ◽  
Group 3 ◽  
Cell Mobilization

Abstract The purpose of this study was to examine the yield of PBSC, mobilized with G-CSF alone, and engraftment kinetics after autologous transplantation in pediatric cancer patients. In 55 patients (median age; 7 years, range 0–21) with various pediatric and adolescent solid tumors, PBSC were mobilized with G-CSF alone, and the yields of PBSC and engraftment following autologous PBSCT were evaluated retrospectively. Patients were categorized according to prior treatment; patients who had received less than 4 or 4 cycles of chemotherapy with/without local irradiation (Group 1: N= 21), patients who received more than 4 cycles of chemotherapy or 3 or more cycles of chemotherapy with extended irradiation (Group 2: N= 23), and patients who received high-dose chemotherapy with stem cell support (Group 3: N= 11). Ten microgram per kg of G-CSF was injected subcutaneously for mobilization when patients showed no influence of previous chemotherapy, and administration was continued for five days. The peaks of CD34+ cells and CFU-GM were observed on day 5 of G-CSF administration essentially in all patients. Aphereses were performed on days 5 and 6 of G-CSF treatment. Mobilization failure was observed in four patients in all groups. Compared with the results in patients mobilized by chemotherapy plus G-CSF (N=18), the progenitor cell yields were lower in those mobilized with G-CSF alone. However, there were no significant differences in WBC engraftment speed compared to the chemotherapy plus G-CSF mobilization group, although platelet recovery was delayed in patients with G-CSF alone, especially in patients in Group 3. The median time taken for ANC and platelet counts to reach 500 and 20K was 12 days (range 8–28) and 15 days (8–55), respectively, in all patients who were mobilized by G-CSF alone except for patients with progressive disease. In summary, mobilization with G-CSF alone can mobilize a sufficient number of CD34+ cells for successful autografting and sustained hematological reconstitution in pediatric patients with cancer, even in heavily pre-treated patients. Mobilization with G-CSF alone might offer some advantages, such as ease of determining a collection schedule without a daily determination of CD34+ cells in the blood, and the avoidance of neutropenic fever and additional transfusion.

A Retrospective Analysis of Mantle Cell Lymphoma Patients Series Treated Upfront by Sequential High Dose Immunochemotherapy Supported by In Vivo Purged Stem Celle Double Autologous Transplantation: A Monocentric Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4949-4949
Author(s):  
Andrea Ferrario ◽  
Giorgia Saporiti ◽  
Nicola Orofino ◽  
Francesco Onida ◽  
Daniele Vincenti ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Lymphoma ◽  
Standard Dose ◽  
Autologous Transplantation ◽  
Disease Free Survival ◽  
High Dose ◽  
Free Survival ◽  
Mantle Cell ◽  
High Dose Cytarabine ◽  
Disease Free

Abstract Abstract 4949 Mantle Cell Lymphoma (MCL) is a rare lymphoma that accounts for 3–10% of all non Hodgkin's Lymphoma in adults. Being associated with rapid progression and high recurrence rate, although some treatment improvements during the last years, it is still considered an incurable disease. In order to overcome the poor outcome obtained with conventional chemotherapy, new treatment strategies using high dose chemotherapy supported by autologous stem cell transplantation (ASCT) have been developed in young patients. In particular the use of high dose cytarabine and rituximab prior to ASCT has been demonstrated to improve outcome in terms of response and disease free survival. The present study is a restrospective analysis conducted in our centre in order to evaluate the outcome of 16 MCL patients treated upfront with sequential high dose immunochemotherapy followed by double ASCT. From 2000 to 2011, 16 MCL patients, eligible for ASCT, have been consecutively treated as follow: a) standard dose phase: APO: doxorubicin, 75 mg/sqm i.v., day 1; prednisone, 60 mg/sqm orally, day 1 to 5 and day 9 to 12; vincristine, 1.4 mg/sqm i.v., day 1 and 8; DHAP: cisplatin 70 mg/sqm, day 1; cytarabin 1500 mg/sqm i.v., days 2–3; dexametasone 40 mg i.v., days 1 to 3; b) rituximab high dose sequence: high dose cyclophosphamide (CTX 5 g/sqm) and high dose cytarabine (Ara-C 2 g/sqm every 12 hours for 6 consecutive days) followed by peripheral blood stem cell (PBSCs) collection; c) high dose melphalan (180 mg/sqm) and high dose mitoxantrone plus melphalan (60 mg/sqm and 180 mg/sqm, respectively) followed by PBSCs infusion. Rituximab (375 mg/sqm) was infused twice after CTX, cytarabine and double autologous transplantation (modified from Gianni et al, Blood, 102, 749, 2003). All patients (9 female and 7 male) had a histological diagnosis of MCL according to the WHO classification criteria; molecular rearrangement of bcl-1 locus was detected by PCR in the bone marrow of 8 patients. The median age at diagnosis was 57 years (range 50–68); 14 patients were in stage IV and 2 in stage III; 2 patients had bulky disease at presentation. Four patients were in overt leukemic phase and 2 had extranodal localization. According to MIPI score, 14 patients (87%) were classified as low risk and 2 (13%) as intermediate risk. Double transplant was performed in all patients except one (who refused it). The standard dose phase, including a median number of 4 cycles (range 3–5), was generally well tolerated, with only one patient experiencing tumor lysis syndrome. After induction, clinical CR was achieved in six patients. PBSCs were successfully collected after both the CTX/rituximab (1.8-9.7×10̂6/Kg) and the Ara-C/rituximab (7.1- 40.0×10̂6/Kg) cycles. At the end of these phases, 7 patients (44%) were in CR while 9 (56%) were in PR. Following transplants, median times to ANC >500/μL were 11 days (range 10–14) in both the procedures, whereas median times to platelet recovery (>50000/μL) were 19 days (range 10–44) after the first transplant and 24 days (range 11–298) after the second one. After a median follow-up of 38 months (range 14–111), 10 patients (62%) were alive (8 in CR, 2 in relapse), whereas 6 died from disease progression. Our study confirmed that in MCL the use of sequential high dose immunochemotherapy including rituximab and high dose cytarabine followed by double autologous transplantation is associated to high remission rates with long-term disease-free survival in a significant proportion of patients. Disclosures: No relevant conflicts of interest to declare.

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