High-Dose Ifosfamide Chemotherapy in a Series of Patients Affected by Myxoid Liposarcoma

Background. To report on the activity of high-dose prolonged-infusion ifosfamide (HDIFX) chemotherapy in a retrospective series of patients affected by myxoid liposarcoma treated at Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy. Patients and Methods. Patients with an advanced myxoid liposarcoma treated with HDIFX (14 g/sqm, i.v., prolonged infusion of 14 days every 28 days) as a single agent between May 2002 and April 2017 were retrospectively reviewed. All pathologic diagnoses were centrally reviewed and molecularly confirmed. Response was evaluated by RECIST, and survival functions were computed by the Kaplan-Meier method. Results. Eleven patients with advanced myxoid liposarcoma were treated with HDIFX (male/female = 9/2, median age 33 years, range 31–75). Among these, 1/11 received HDIFX in first line, 5/11 in second line, 3/11 in third line, and 2/11 in fourth line for a median course number of 3 (range 2–7). No RECIST objective responses were observed. Overall median progression-free survival was 1,9 months. Median overall survival was 37 months. At a median follow-up of 115 months, 1 patient is alive. Conclusions. In this series of patients affected by advanced myxoid liposarcoma, chemotherapy with HDIFX was essentially inactive.

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Survival and toxicity outcomes in patients age 40 or older with relapsed metastatic germ cell tumors (mGCT) treated with high-dose chemotherapy (HDCT) and autologous peripheral-blood stem cell transplant (PBSCT).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.522 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 522-522

Author(s):

Nabil Adra ◽

Costantine Albany ◽

Rafat Abonour ◽

Mohammad Issam Abu Zaid ◽

Dannillo Pereira ◽

...

Keyword(s):

Salvage Therapy ◽

Germ Cell Tumors ◽

Progression Free Survival ◽

High Dose Chemotherapy ◽

High Dose ◽

Cell Transplant ◽

Indiana University ◽

Free Survival ◽

Kaplan Meier

522 Background: HDCT plus PBSCT is effective salvage therapy for relapsed mGCT but has potential toxicity which can be more pronounced in older patients. We report survival and toxicity outcomes in pts with relapsed mGCT age ≥ 40 at time of HDCT. Methods: 440 consecutive pts with relapsed mGCT were treated with HDCT and PBSCT with tandem cycles at Indiana University (IU) between 2004-2017 per our previous reported regimen (N Engl J Med 2007; 357: 340-8). Kaplan-Meier methods were used for progression free survival (PFS) analysis. Results: 110 pts were age ≥ 40 while 330 pts were age < 40. Among pts age ≥ 40, median AFP was 6.6 (range, 1-2,709) and median hCG was 5.3 (range, 1-42, 453). Of the 110 pts age ≥ 40, 75 had complete remission without relapse during a median follow-up of 23 months. There were 3 treatment-related deaths. Conclusions: HDCT plus PBSCT is safe and effective salvage therapy in pts age ≥ 40 with relapsed mGCT. [Table: see text]

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Promising Efficacy with the New Anti-CD20 Antibody GA101 In Heavily Pre-Treated NHL Patients – Updated Results with Encouraging Progression Free Survival (PFS) Data From a Phase II Study In Patients with Relapsed/Refractory Indolent NHL (iNHL)

Blood ◽

10.1182/blood.v116.21.2868.2868 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2868-2868 ◽

Cited By ~ 9

Author(s):

Gilles Andre Salles ◽

Franck Morschhauser ◽

Catherine Thieblemont ◽

Philippe Solal-Céligny ◽

Thierry Lamy ◽

...

Keyword(s):

Febrile Neutropenia ◽

Phase Ii ◽

Single Agent ◽

Progression Free Survival ◽

Survival Advantage ◽

High Dose ◽

Free Survival ◽

Cd20 Antibody ◽

Anti Cd20

Abstract Abstract 2868 Background: GA101 is the first type II, glycoengineered and humanized monoclonal anti-CD20 antibody with Phase I results (NHL/CLL) (Salles, ASH 2008, 2009; Cartron, EHA 2009; Morschhauser, ASH 2009; Sehn, ASH 2009) and phase II results (Indolent NHL) previously reported (EHA 2010). Based on an additional 1 year follow-up period, we report updated efficacy and safety results with single agent GA101, presenting new and encouraging progression free survival (PFS) data indicating a survival advantage of those patients randomized to the high dose cohort (1600/800mg). Methods: 40 eligible patients were randomized to receive GA101 in a low-dose (LD, n=18) or a high dose (HD, n=22) cohort. GA101 was given on d1, d8, d22 and q21 days for total of 9 infusions. In the LD cohort, GA101 was given 400mg all infusions; in the HD cohort, d1 and d8 at 1600mg and 800mg for subsequent infusions. Primary endpoint was end of treatment response (EOR), assessed 4 weeks after last infusion (44 weeks after treatment start). Secondary objectives were safety, pharmacokinetics and PFS. Results: Patients (Table 1) were heavily pre-treated (median 3 prior therapies) with 55% of patients not responding to or relapsing within six months after a previous rituximab-containing regimen (rituximab refractory). There were no significant differences in demographics and baseline tumour burden between the two cohorts and 75% of patients completed all scheduled 9 infusions. EOR was 17% (3 PR, 6 SD, 7 PD, 2 UNK) in the LD cohort, and 55% (2 CR, 10 PR, 6 SD, 4 PD) in the HD cohort. Of note, 6/22 rituximab-refractory patients (5 HD, 1 LD) responded, with a EOR response of 50% in rituximab-refractory patients in the HD cohort (5/10). Responses occurred across all FcγIIIR genotypes in both cohorts: of 3 responders in LD, 2 patients with F/F genotype, other unknown; of 12 responders in HD; 5 F/F, 7 F/V. Responding patients from both LD and HD groups appeared to have higher GA101 plasma concentrations compared to non-responding patients. Median PFS was 6 months [1.1-16.9+ months] and 11.3 months [1.8-14.2+ months] for the LD and HD cohorts respectively (Hazard ratio 0.55 [95% CI 0.24;1.27]). Of 15 responding patients at EOR, 9 have an ongoing response in follow-up (LD=2, HD=7), with 2 PRs converting to CR (LD=1, HD=1) and another PR to CRu (HD). In addition 2 patients (LD=1, HD=1) in follow-up converted from EOR SD to PR, one patient with an ongoing response and the other subsequently relapsing, therefore 10 patients currently have an ongoing response. GA101 was well tolerated in both cohorts with the most common AEs being infusion related reactions (LD 72%, HD 73% of patients), mostly of G1-2. During treatment, related G3-4 hematological AEs were transient neutropenia (n = 3 in HD), febrile neutropenia (n=1 in HD) and thrombocytopenia (n = 1 in HD), four patients experienced at least one G3-4 Infection (LD n=1, HD n=3). Nine patients experienced a total 12 SAEs during treatment period, with 4 related to GA101 (HD n=4; herpes zoster, febrile neutropenia, pancreatitis, neutropenia) and 2 patients in the additional follow-up period, with SAEs of pyrexia (LD) and bacteraemia (HD), both unrelated to GA101. In addition, no B-cell recovery has been observed to date. Conclusion: GA101 single agent is well tolerated, with promising efficacy and provides very encouraging PFS data, in this group of heavily pre-treated relapsed and refractory iNHL patients, indicating a survival advantage for those patients in the HD cohort (1600/800mg). Disclosure: Salles: Roche: Consultancy, Honoraria. Morschhauser:Roche: Consultancy, Honoraria. Wenger:Roche: Employment. Birkett:Roche: Employment. Cartron:Roche: Consultancy, Honoraria; GSK: Honoraria.

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Clinical Presentation, Natural History, and Therapeutic Approach in Patients with Solitary Fibrous Tumor: A Retrospective Analysis

Sarcoma ◽

10.1155/2020/1385978 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

P. Schöffski ◽

I. Timmermans ◽

D. Hompes ◽

M. Stas ◽

F. Sinnaeve ◽

...

Keyword(s):

Solitary Fibrous Tumor ◽

Systemic Therapy ◽

Median Overall Survival ◽

Progression Free Survival ◽

Response Rates ◽

Free Survival ◽

Metachronous Metastasis ◽

Third Line ◽

Fibrous Tumor

Background. Solitary fibrous tumor (SFT) is a rare variant of soft tissue sarcoma (STS). Materials and Methods. We reviewed SFT patients (pts) treated at our institution between 12/1990 and 09/2017. Results. We identified 94 pts with a median follow-up (mFU) of 4.7 years (range: 0.1–21.53). Primary sites were the chest (33%), abdomen (21.3%), brain (12.8%), and extremities (9.6%); 6.4% of pts presented with synchronous metastasis. Median overall survival (mOS) from the first diagnosis was 56.0 months (m) (0.3–258.3). Doege–Potter syndrome was seen in 2.1% of pts. Primary resection was performed in 86 pts (91.5%). Median progression-free survival was 34.1 m (1.0–157.1), and 43% of pts stayed SFT-free during FU. Local recurrence occurred in 26.7% after a mFU of 35.5 m (1.0–153.8), associated with an OS of 45.1 m (4.7–118.2). Metachronous metastasis occurred in 30.2% after a mFU of 36.0 m (0.1–157.1). OS in metastatic pts was 19.0 m (0.3–149.0). Systemic therapy was given to 26 pts (27.7%) with inoperable/metastatic disease. The most common (57.7%) upfront therapy was doxorubicin, achieving responses in 13.3% of pts with a PFS of 4.8 m (0.4–23.8). In second line, pts were treated with ifosfamide or pazopanib, the latter achieving the highest response rates. Third-line treatment was heterogeneous. Conclusion. SFT is an orphan malignancy with a highly variable clinical course and a considerable risk of local failure and metachronous metastasis. Surgery is the only curative option; palliative systemic therapy is used in inoperable/metastatic cases but achieves low response rates. The highest response rates are seen with pazopanib in second/third line.

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Determining the utility of intraoperative magnetic resonance imaging for transsphenoidal surgery: a retrospective study

Journal of Neurosurgery ◽

10.3171/2013.9.jns122207 ◽

2014 ◽

Vol 120 (2) ◽

pp. 346-356 ◽

Cited By ~ 30

Author(s):

Jan Coburger ◽

Ralph König ◽

Klaus Seitz ◽

Ute Bäzner ◽

Christian Rainer Wirtz ◽

...

Keyword(s):

Transsphenoidal Surgery ◽

High Field ◽

Progression Free Survival ◽

Residual Tumor ◽

Conventional Group ◽

Free Survival ◽

Kaplan Meier ◽

Remission Rates ◽

Biochemical Remission

Object Intraoperative MRI (iMRI) provides updated information for neuronavigational purposes and assessments on the status of resection during transsphenoidal surgery (TSS). The high-field technique additionally provides information about vascular structures at risk and precise information about extrasellar residual tumor, making it readily available during the procedure. The imaging, however, extends the duration of surgery. To evaluate the benefit of this technique, the authors conducted a retrospective study to compare postoperative outcome and residual tumor in patients who underwent conventional microsurgical TSS with and without iMRI. Methods A total of 143 patients were assessed. A cohort of 67 patients who had undergone surgery before introduction of iMRI was compared with 76 patients who had undergone surgery since iMRI became routine in TSS at the authors' institution. Residual tumor, complications, hormone dependency, biochemical remission rates, and improvement of vision were assessed at 6-month follow-up. A volumetric evaluation of residual tumor was performed in cases of parasellar tumor extension. Results The majority of patients in both groups suffered from nonfunctioning pituitary adenomas. At the 6-month follow-up assessment, vision improved in 31% of patients who underwent iMRI-assisted surgery versus 23% in the conventional group. One instance of postoperative intrasellar bleeding was found in the conventional group. No major complications were found in the iMRI group. Minor complications were seen in 9% of patients in the iMRI group and in 5% of those in the conventional group. No differences between groups were found for hormone dependency and biochemical remission rates. Time of surgery was significantly lower in the conventional treatment group. Overall a residual tumor was found after surgery in 35% of the iMRI group, and 41% of the conventional surgery group harbored a residual tumor. Total resection was achieved as intended significantly more often in the iMRI group (91%) than in the conventional group (73%) (p < 0.034). Patients with a planned subtotal resection showed higher mean volumes of residual tumor in the conventional group. There was a significantly lower incidence of intrasellar tumor remnants in the iMRI group than in the conventional group. Progression-free survival after 30 months was higher according to Kaplan-Meier analysis with the use of iMRI, but a statistically significant difference could not be shown. Conclusions The use of high-field iMRI leads to a significantly higher rate of complete resection. In parasellar tumors a lower residual volume and a significantly lower rate of intrasellar tumor remnants were shown with the technique. So far, long-term follow-up is limited for iMRI. However, after 2 years Kaplan-Meier analyses show a distinctly higher progression-free survival in the iMRI group. No significant benefit of iMRI was found for biochemical remission rates and improvement of vision. Even though the surgical time was longer with the adjunct use of iMRI, it did not increase the complication rate significantly. The authors therefore recommend routine use of high-field iMRI for pituitary surgery, if this technique is available at the particular center.

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Evaluation of intensive postremission chemotherapy for adults with acute nonlymphocytic leukemia using high-dose cytosine arabinoside with L-asparaginase and amsacrine with etoposide.

Journal of Clinical Oncology ◽

10.1200/jco.1987.5.6.918 ◽

1987 ◽

Vol 5 (6) ◽

pp. 918-926 ◽

Cited By ~ 26

Author(s):

M S Tallman ◽

F R Appelbaum ◽

D Amos ◽

R S Goldberg ◽

R B Livingston ◽

...

Keyword(s):

Cytosine Arabinoside ◽

Disease Free Survival ◽

High Dose ◽

Acute Nonlymphocytic Leukemia ◽

Free Survival ◽

Kaplan Meier ◽

To Receive ◽

Disease Free ◽

Historical Controls

In order to test the toxicity and efficacy of intensive postremission therapy with high-dose cytosine arabinoside with L-asparaginase and amsacrine with etoposide in adults with acute nonlymphocytic leukemia (ANL), 100 adults (ages 19 to 75) with previously untreated ANL were entered into a study using six sequential cycles of chemotherapy. Cycles 1 (induction), 3, and 5 included conventional doses of daunomycin, cytosine arabinoside, 6-thioguanine, vincristine (VCR), and prednisone. Cycle 2 was cytosine arabinoside 3 g/m2 intravenously (IV) every 12 hours for four doses, followed by L-asparaginase 10,000 U intramuscularly (IM) at hour 42; this combination was repeated 1 week later. Cycle 4 included amsacrine 120 mg/m2/d and etoposide 100 mg/m2/d, both IV for five days, and cycle 6 was three monthly courses of VCR on day 1, and prednisone, mercaptopurine, and methotrexate each for five days. Seventy-four patients (74%) achieved complete remission (CR) (51 with cycle 1 and 23 after cycle 2). The overall disease-free survival (DFS) for patients achieving CR is 27% at 3 years by Kaplan-Meier analysis, while for patients achieving CR with cycle 1 it is 34%. The actuarial probability of being free from relapse at 3 years for patients achieving CR is 34%. Sixteen of the 74 CR patients (22%) died in CR while continuing to receive intensive chemotherapy, including 12 (18%) who succumbed to infection (nine bacterial, three fungal). After a median follow-up of 20 months, 36 patients have relapsed and 21 remain alive in CR. Intensive consolidation with high-dose cytosine arabinoside, amsacrine, and etoposide can modestly prolong DFS compared with historical controls. However, relapse continued to be a major problem and, in addition, with more aggressive consolidation therapy, infection during marrow aplasia resulted in a significant number of deaths.

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Phase I/II study incorporating intravenous hydroxyurea into high-dose chemotherapy for patients with primary refractory or relapsed and refractory intermediate-grade and high-grade malignant lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.1995.13.5.1089 ◽

1995 ◽

Vol 13 (5) ◽

pp. 1089-1095 ◽

Cited By ~ 8

Author(s):

W P Vaughan ◽

E Kris ◽

J Vose ◽

P J Bierman ◽

P Gwilt ◽

...

Keyword(s):

Phase I ◽

Continuous Infusion ◽

Progression Free Survival ◽

High Dose Chemotherapy ◽

Rank Test ◽

High Dose ◽

Hematopoietic Stem ◽

Free Survival ◽

Stem Cell Rescue

PURPOSE A phase I/II study was performed to evaluate the incorporation of hydroxyurea (HU) into high-dose chemotherapy of non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS Thirty-eight patients with primary refractory and refractory relapsed NHL were treated with carmustine (BCNU) (300 mg/m2 on day -8), cyclophosphamide (Cy) (2.5 g/m2/d on days -8 and -7), etoposide (E) (150 mg/m2 every 12 hours on days -6, -5, and -4), and HU (BCHE) with autologous hematopoietic stem-cell rescue. Twenty-one patients received HU in a dose escalation of 2 to 12 g/m2 intravenously (IV) by 72-hour continuous infusion. When the IV formulation was not available, 17 patients were given 18 g/m2 of HU orally in divided doses every 6 hours over the same 72-hour period. RESULTS The dose-limiting toxicity of 72-hour continuous infusion HU in this regimen was mucositis. Endotracheal intubation was necessary to protect the airway in two thirds of patients treated at 12 g/m2. Six patients (oral BCHE, five of 17; IV BCHE, one of 21) died with nonresponding or progressive disease and, at least in part, from the complications of the high-dose chemotherapy. Seventeen patients (45%) achieved complete remission (CR). More patients treated with IV BCHE achieved CR than patients treated with oral BCHE (12 of 21 v five of 17; P < .1, chi 2 test). Nine patients (two of 17 oral BCHE and seven of 21 IV BCHE) remain disease-free as of January 31, 1994, with a minimum follow-up time of 3 years. The lower mortality and higher response rate with IV BCHE translated into a significantly superior probability of progression-free survival (PFS) (33% at 4 year v 12% for oral BCHE; P = .048, log-rank test). CONCLUSION High-dose BCHE is effective treatment for primary refractory and refractory relapsed NHL. Continuous IV HU appears to be less toxic and more effective than intermittent oral HU in this regimen.

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Necessity of Intraventricular Chemotherapy with the Modified Bonn Protocol in Primary CNS Lymphoma (PCNSL) Patients.

Blood ◽

10.1182/blood.v108.11.2452.2452 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2452-2452

Author(s):

Ingo G.H. Schmidt-Wolf ◽

Hendrik Pels ◽

Annika Juergens ◽

Axel Glasmacher ◽

Holger Schulz ◽

...

Keyword(s):

Primary Cns Lymphoma ◽

Progression Free Survival ◽

Cns Lymphoma ◽

High Dose ◽

Free Survival ◽

Intraventricular Chemotherapy ◽

High Infection ◽

Intraventricular Treatment

Abstract Background: Treatment of primary CNS lymphoma (PCNSL) with a combined systemic and intraventricular chemotherapy (Bonn protocol) has achieved an overall response rate (ORR) of 84% and long term complete remissions in a substantial fraction of patients younger than 60 years. Purpose: Due to a high infection rate of the Ommaya reservoir the question was addressed if intraventricular treatment is dispensable in this polychemotherapy protocol. Patients and Methods: Fifty patients with histologically confirmed PCNSL were enrolled onto a phase II-study evaluating chemotherapy without radiotherapy and without intraventricular treatment. A high-dose methotrexate (MTX) (cycles 1,2,4,5) and cytarabine (ara-C) (cycles 3,6) based systemic therapy (including dexamethasone, vinca-alkaloids, ifosfamide and cyclophosphamide) was administered. Results: In an ongoing trial thirty-five of 50 patients (18 pat. < 60 years, 17 pat. over 60 years) are yet assessable for response after a median follow up of nine months (range: 1 to 26 months). In 18 patients < 60 years, the ORR was 78%. However, median time to treatment failure (TTF) was eight months, and median progression free survival (PFS) only 7 months according to frequent early relapses. Conclusions: Early relapses are frequent in younger patients treated with the modified Bonn protocol without intraventricular treatment despite a high ORR. These preliminary results support the assumption that intraventricular treatment is essential to achieve sustained remissions after successful treatment of PCNSL.

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Bortezomib, Thalidomide, and Dexamethasone as Induction Therapy for Patients with Symptomatic Multiple Myeloma.

Blood ◽

10.1182/blood.v110.11.3605.3605 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3605-3605 ◽

Cited By ~ 1

Author(s):

Jonathan L. Kaufman ◽

Charise Gleason ◽

Leonard Heffner ◽

Sagar Lonial

Keyword(s):

Induction Therapy ◽

Progressive Disease ◽

Response Rate ◽

Progression Free Survival ◽

High Response Rate ◽

High Dose ◽

High Dose Therapy ◽

Free Survival ◽

One Year

Abstract The optimal induction regimen for patients with symptomatic myeloma who are eligible for transplantation is currently unknown. While thalidomide and dexamethasone is an effective regimen, it only has a 60 to 65% response rate and few complete responses (CR). Bortezomib based inductions have demonstrated a high response rate and an improved CR as well. Recently the IFM reported the initial results of the randomized bortezomib plus dexamethasone versus VAD induction followed by transplant, which demonstrated that fewer patients treated with bortezomib required tandem transplants. Wang et al reported a high induction response rate with the combination of BTD for only 2 cycles given over a 28 day cycle. Here we report our experience with the combination of BTD as induction therapy. 38 patients with symptomatic myeloma were treated with BTD as induction therapy. Patients received standard dose and schedule bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11 with thalidomide at 100 mg/day, and 8 days of 40 mg dexamethasone every 21 days. The median age was 58 years (38–70) with 19 males. This was first line therapy for 29 patients, second line for 7 patients and 3rd line for 2. 12 patients had ISS stage 2 and 8 had ISS stage 3. The median β2M was 3.4 (1.66–41.89). Median creatinine was 1.1 (0.6–21.0). Nineteen patients had an IgG paraprotein, 6 an IgA, and 16 patients had light chain disease. The median number of cycles administered was 4 (2–8). Fifteen patients developed neuropathy of any grade. One patient developed grade 3 neuropathy. The overall response rate (CR, VGPR, plus PR) was 92%, with 58% of patients achieving a VGPR or better, and 21% of patients achieving an immunofixation negative CR. 1 patient had a minimal response and 2 patients had progressive disease (both patients presented with plasma cell leukemia). These two patients were treated with the combination of BTD with PACE chemotherapy. One of the two died from progressive disease and the other patient remains in complete remission after high dose therapy and autologous transplantation. 29 patients had consolidation therapy with high dose melphalan and autologous peripheral blood stem cell transplantation. Eight patients have collected stem cells without proceeding with immediate consolidation therapy. After a median follow up of 373 days, median progression free survival and overall survival have not been reached. One year overall survival is 97%. One year progression free survival is 87%. In conclusion, we report a very high response rate with a short course of bortezomib, thalidomide and dexamethasone with an acceptable toxicity profile. Follow up of patients in CR treated without high dose therapy and autologous transplant is in progress. Further studies of this active regimen are warranted.

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Autologous Transplantation in De Novo Non-Promyelocytic Acute Myeloid Leukemia (AML) Patients in First Complete Remission (CR1) with Peripheral Blood Stem Cell (PBSC) Collection Following Consolidation with High-Dose Cytarabine and Etoposide: A Single Institution Experience

Blood ◽

10.1182/blood.v112.11.4461.4461 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4461-4461

Author(s):

Eugene Choi ◽

Lingyi Chen ◽

Srikanth Nagalla ◽

Vamshi Kaveti ◽

Regina Mullaney ◽

...

Keyword(s):

De Novo ◽

Disease Free Survival ◽

High Dose ◽

Free Survival ◽

Kaplan Meier ◽

Cd34 Cells ◽

High Dose Cytarabine ◽

Lost To Follow Up ◽

Disease Free

Abstract INTRODUCTION: Autologous PBSC transplant is an important yet evolving treatment modality for patients with AML. However, the ideal mobilization regimen from which to collect PBSC remains in question. Previous reports have indicated that highdose cytarabine with etoposide is both safe and effective in terms of successful PBSC procurement, subsequent engraftment, and disease outcome. METHODS: At our institution from 1994 to 2007, 38 consecutive patients with de novo non-promyelocytic AML in first complete remission following conventional induction chemotherapy were consolidated with high-dose cytarabine (2000mg/m2 IV q12h × 8 doses, days 1–4) and etoposide (40mg/kg IV over 96h) followed by G-CSF 5 mg/kg subcutaneously starting d14 until completion of PBSC collection. Patients underwent myeloablative therapy with busulfan (1mg/kg po q6h × 16 doses, days –7 to -4) and etoposide (60 mg/kg IV over 10h, day -3) with PBSC infusion occurring on day 0 with daily G-CSF 5 mg/kg. Data regarding stem cell yield, engraftment and patient outcome was collected retrospectively. RESULTS: The average patient age was 44 years (range 19–70). Following consolidation, at least 2×106 CD34 cells/kg were isolated from all 38 patients with a median of 9.4×106 (range 2.2–43) CD34 cells/kg over a mean of 4 collections (range 1–11). Overall, 36 of 38 (95%) remained in CR and went onto PBSC transplant (one died from infectious complications during consolidation, one relapsed before transplant). The median number of stem cells infused was 8.8×106 CD 34 cells/kg (range 2.2–47). All 36 patients engrafted with the mean number of days to neutrophil recovery (ANC>500) being 11 (range 8–17) and the mean number of days to platelet recovery (>20,000) being 12 (range 8–19). Disease-free outcomes in patients undergoing PBSC transplant while in CR1 are presented in Figure 1. The 3y overall survival in all pts was 66%, and 56% at 5y. For good-risk cytogenetic patients, 3y OS was 78% and the 5y OS was 75%. For intermediate-risk cytogenetic patients, OS was 47% and 36% at 3y and 5y respectively. Three patients with poor cytogenetics were autulogously transplanted. One patient relapsed at day 111 and expired at day 450. The second patient remains in CR at day 246. The third patient relapsed at day 104 and expired at day 322. CONCLUSION: In patients with de novo non-promyelocytic AML in CR1, consolidation with high-dose cytarabine plus etoposide is safe and provides excellent yield of PBSCs upon growth factor accelerated hematological recovery. Subsequent engraftment after autologous transplanation is rapid. Our outcomes support the viability of this regimen in patients with good and intermediate-risk cytogenetics. Figure 1: Kaplan-Meier analysis of disease-free survival following autologous PBSC transplant. Cytogenetic analysis was unavailable in 5 patients, and 1 patient was lost to follow-up. Figure 1:. Kaplan-Meier analysis of disease-free survival following autologous PBSC transplant. Cytogenetic analysis was unavailable in 5 patients, and 1 patient was lost to follow-up.

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A Novel Reduced Intensity Conditioning Can Induce a High Incidence of Sustained Donor Engraftment After Double Unit Cord Blood Transplantation (CBT) without Anti-Thymocyte Globulin

Blood ◽

10.1182/blood.v116.21.2351.2351 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2351-2351

Author(s):

Doris M Ponce ◽

Craig Sauter ◽

Marissa Lubin ◽

Anne Marie Gonzales ◽

Glenn Heller ◽

...

Keyword(s):

Risk Factors ◽

Acute Gvhd ◽

Progression Free Survival ◽

High Dose ◽

Free Survival ◽

Prior Therapy ◽

Cd34 Cells ◽

High Incidence ◽

Related Mortality

Abstract Abstract 2351 CBT can be curative for patients with high-risk hematologic malignancies. However, patients of older age, those with extensive prior therapy, or significant co-morbidities may not tolerate high-dose myeloablative conditioning. Reduced intensity (RI) or non-myeloablative (NMA) conditioning has been successfully used in CBT, especially in patients with lymphomas. However, patients with myeloid malignancies without extensive prior therapy have an increased risk of graft rejection following NMA CBT. Further, the addition of anti-thymocyte globulin (ATG) to enhance engraftment increases the risk of serious infections and Epstein-Barr virus post-transplant lymphoproliferative disease, and could increase the risk of relapse. Therefore, we investigated the efficacy and safety of a novel ATG-free RI conditioning prior to double unit CBT in patients with acute leukemias and myelodysplasia with the hypothesis that this regimen can induce a high incidence of sustained donor engraftment. Conditioning consisted of cyclophosphamide 50 mg/kg (day -6), fludarabine 30 mg/m2/day × 5 (days -6 to -2), thiotepa 5 mg/kg/day × 2 (days -5 and -4), and total body irradiation 200 cGy × 2 (days -2 and -1). All patients received cyclosporine-A and mycophenolate mofetil for graft-versus-host disease (GVHD) prophylaxis. Between 10/01/07-04/30/10, 20 patients were transplanted. The median age was 56 years (range 18–69). Thirteen (65%) had AML (9 CR1, 4 CR2), 4 (20%) had ALL (3 CR1, 1 CR3), and 3 (15%) had MDS (with one patient also having follicular lymphoma). The majority had high-risk disease. Indications for RI conditioning were the risk factors for transplant-related mortality (TRM) with high-dose conditioning of age ≥50 years, and/or extensive prior therapy, and/or significant co-morbidities. Thirteen patients had only 1 of these risk factors, whereas 7 had ≥2 risk factors. Units were predominantly 4–5/6 HLA-matched to the recipient (one 6/6, twenty-four 5/6, fifteen 4/6). The median infused cell doses of the larger units were 2.7 × 107 total nucleated cells/kg (range 1.46–5.56) and 0.95 × 105 CD34+ cells/kg (range 0.35–3.32), and 1.89 × 107/kg total nucleated cells/kg (range 1.42–2.47) and 0.59 × 105/kg CD34+ cells/kg (range 0.18–1.52) for the smaller units, respectively. The cumulative incidence of sustained donor engraftment at day 45 was 95% (95%CI: 81–100). The single patient with graft failure was 100% donor in the day 21 bone marrow, but died early post-transplant of multi-organ failure without count recovery. The median time to neutrophil recovery ≥0.5 × 109/l was 25 days (range 13–43). The median total donor chimerism in the day 21 bone marrow was 94% (both units combined, range 71–100), and sustained engraftment was accounted for by one unit in 18/19 engrafting patients. The incidence of grade II-IV acute GVHD at day 100 was 55% (95%CI: 32–78), and 46% (95%CI: 21–71) of patients have had late acute GVHD requiring ongoing therapy or chronic GVHD to date. The incidence of day 100 transplant-related mortality (TRM) was 20% (95%CI: 2–38). Notably, none of the 13 patients with only one risk factor died of transplant-related causes. By contrast, 5/7 (71%) patients with ≥2 risk factors died of TRM by day 100 (p=0.03, Table 1). Two additional patients died of relapse. With a median follow-up of 13 months (range 3–31), 1 year progression-free survival is 74% (95%CI: 55–94) (Figure 1). We demonstrate that this ATG-free RI conditioning is associated with a high incidence of sustained donor engraftment, and acceptable toxicities in older patients without other risk factors. While longer follow-up is needed, progression-free survival is encouraging provided multiple risk factors are not present. This conditioning combined with double unit grafts warrants further investigation, and may also be a promising alternative to high-dose conditioning in younger patients. Table 1. Day 100 TRM according to number of risk factors (age ≥50 years, extensive prior therapy, significant co-morbidities). Risk Factors Day 100 TRM P Value 1 (N = 13) 0/13 (0%) 0.03 ≥2 (N = 7) 5/7 (71%) Figure 1. Progression-Free Survival At 1 Year Figure 1. Progression-Free Survival At 1 Year Disclosures: Giralt: Celgene: Honoraria, Speakers Bureau; Millenium: Honoraria, Speakers Bureau.

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