AML Patients In First CR with Intermediate Risk Cytogenetic and High Level of CD34+ Mobilization Have Better DFS After Allogeneic Transplantation.

Abstract Abstract 4563 AML patients having a high apheretic yield in CD34+ cells during mobilization have a poor prognosis, independently from cytogenetic risk (Feller 2004, Keating 2004). It is however not known if prognostic value of PBSC mobilization is retained after different post remissional treatment and clinical usefullness of this prognostic information in dealing with intermediate cytogenetic group patients, the more represented AML subgroup in which post remissional therapy is still a controversial issue. METHODS A group of 64 AML adult patients in 1st CR was prospectively studied. PBSC mobilization was attempted following first consolidation course. Cytogenetic assessment at diagnosis was available in 95% of patients. Post remissional treatment was chosen based on cytogenetic risk, sibling donor availability and presence of others prognostic factors, MUD transplants were proposed in cytogenetic high risk patients or in selected young patients with intermediate cytogenetic, Autologous HSC Transplantation was proposed when allogeneic transplant was felt not indicated, no further therapy was administered in patients deemed ineligible for any kind of transplantation. Prognostic significance of CD34+ cells was evaluated measuring DFS in groups of patients identified from value of CD34+ peak in respect to 50th percentile (CD34 peak: 65×10e6/L) and 75th percentile (197×10e6/L). Those patients having a CD34+ cell peak below median value (65×10e6/L) were categorised as LOW MOBILIZER, those having a CD34+ peak between 65 and 197 ×10e6/L were categorised as GOOD MOBILIZER, and those having a CD34+ peak over 75th percentiles (197 ×10e6/L) were categorised as SUPERMOBILIZER. RESULTS In our serie 40% of patients received an Allogeneic transplant after a myeloablative treatment, 49% an autologous transplant while 11% no further chemotherapy. Disease Free Survival (DFS) was 60%. CD34+ peak during mobilization, evaluated as a continuous variable, in a Cox regression model resulted important for DFS (hazard ratio:1.001; p=0.01). Importance of CD34+ peak was maintained also when the stratum of patients with intermediate cytogenetic risk was analysed (DFS: p=0.002). POOR MOBILIZER, GOOD MOBILIZER and SUPERMOBILIZER patients had statistically different DFS when cases were analysed as a whole (DFS: POOR M.: 70%; GOOD M. 50%; SUPER M: 30%; log rank: p=0.05); mobilizing efficiency was important for DFS also in intermediate cytogenetic group (DFS: POOR M. 70%; GOOD M. 40% DFS; SUPER M. 28%; log rank p= 0.02), importance was maintained also in patients treated by allogeneic transplantation or with autologous transplantation (fig.1). When allogeneic transplantation was compared to the group of patients receiving autologous transplantation or other post remissional strategies both in the cases as a whole and in the stratum of intermediate cytogenetic (table 1), the group of POOR mobilizer had after autologous transplants results non different from patients receiving allogeneic transplantation, however, the group of GOOD mobilizer patients had after allogeneic transplants a DFS significantly better compared to other treatment while SUPER mobilizer patients had poor results also when allogeneic transplantation was employed. In conclusion in AML in 1st CR, evaluation of CD34 peak during mobilization is a parameter providing prognostic informations useful also within intermediate cytogenetic group. Disclosures: No relevant conflicts of interest to declare.

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A Modified HIV1-Based Lentiviral Vector Can Transduce Rhesus Hematopoietic Repopulating Cells as Efficiently as An SIV Vector in An Autologous Transplantation Model.

Blood ◽

10.1182/blood.v114.22.692.692 ◽

2009 ◽

Vol 114 (22) ◽

pp. 692-692

Author(s):

Naoya Uchida ◽

Phillip W Hargrove ◽

Kareem Washington ◽

Coen J. Lap ◽

Matthew M. Hsieh ◽

...

Keyword(s):

T Cells ◽

Blood Cells ◽

Conflicts Of Interest ◽

Lentiviral Vector ◽

Autologous Transplantation ◽

Vector System ◽

Transduction Efficiency ◽

Large Animal ◽

Hematopoietic Stem ◽

Cd34 Cells

Abstract Abstract 692 HIV1-based vectors transduce rhesus hematopoietic stem cells poorly due to a species specific block by restriction factors, such as TRIM5αa which target HIV1 capsid proteins. The use of simian immunodeficiency virus (SIV)-based vectors can circumvent this restriction, yet use of this system precludes the ability to directly evaluate HIV1-based lentiviral vectors prior to their use in human clinical trials. To address this issue, we previously developed a chimeric HIV1 vector (χHIV vector) system wherein the HIV1-based lentiviral vector genome is packaged in the context of SIV capsid sequences. We found that this allowed χHIV vector particles to escape the intracellular defense mechanisms operative in rhesus hematopoietic cells as judged by the efficient transduction of both rhesus and human CD34+ cells. Following transplantation of rhesus animals with autologous cell transduced with the χHIV vector, high levels of marking were observed in peripheral blood cells (J Virol. 2009 Jul. in press). To evaluate whether χHIV vectors could transduce rhesus blood cells as efficiently as SIV vectors, we performed a competitive repopulation assay in two rhesus macaques for which half of the CD34+ cells were transduced with the standard SIV vector and the other half with the χHIV vector both at a MOI=50 and under identical transduction conditions. The transduction efficiency for rhesus CD34+ cells before transplantation with the χHIV vector showed lower transduction rates in vitro compared to those of the SIV vector (first rhesus: 41.9±0.83% vs. 71.2±0.46%, p<0.01, second rhesus: 65.0±0.51% vs. 77.0±0.18%, p<0.01, respectively). Following transplantation and reconstitution, however, the χHIV vector showed modestly higher gene marking levels in granulocytes (first rhesus: 12.4% vs. 6.1%, second rhesus: 36.1% vs. 27.2%) and equivalent marking levels in lymphocytes, red blood cells (RBC), and platelets, compared to the SIV vector at one month (Figure). Three to four months after transplantation in the first animal, in vivo marking levels plateaued, and the χHIV achieved 2-3 fold higher marking levels when compared to the SIV vector, in granulocytes (6.9% vs. 2.8%) and RBCs (3.3% vs. 0.9%), and equivalent marking levels in lymphocytes (7.1% vs. 5.1%) and platelets (2.8% vs. 2.5)(Figure). Using cell type specific surface marker analysis, the χHIV vector showed 2-7 fold higher marking levels in CD33+ cells (granulocytes: 5.4% vs. 2.7%), CD56+ cells (NK cells: 6.5% vs. 3.2%), CD71+ cells (reticulocyte: 4.5% vs. 0.6%), and RBC+ cells (3.6% vs. 0.9%), and equivalent marking levels in CD3+ cells (T cells: 4.4% vs. 3.3%), CD4+ cells (T cells: 3.9% vs. 4.6%), CD8+ cells (T cells: 4.2% vs. 3.9%), CD20+ cells (B cells: 7.6% vs. 4.8%), and CD41a+ cells (platelets: 3.5% vs. 2.2%) 4 months after transplantation. The second animal showed a similar pattern with higher overall levels (granulocytes: 32.8% vs. 19.1%, lymphocytes: 24.4% vs. 17.6%, RBCs 13.1% vs. 6.8%, and platelets: 14.8% vs. 16.9%) 2 months after transplantation. These data demonstrate that our χHIV vector can efficiently transduce rhesus long-term progenitors at levels comparable to SIV-based vectors. This χHIV vector system should allow preclinical testing of HIV1-based therapeutic vectors in the large animal model, especially for granulocytic or RBC diseases. Disclosures: No relevant conflicts of interest to declare.

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Outcome of Patients with Multiple Myeloma (MM) After 1st Relapse Following Front-Line Treatment with Autologous Stem Cell Transplantation (ASCT): Impact of Early Reduced Intensity Allogeneic Transplantation (RICALLO)

Blood ◽

10.1182/blood.v118.21.4533.4533 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4533-4533

Author(s):

Reza Tabrizi ◽

Stephane Vigouroux ◽

Gerald Marit ◽

Arnaud Pigneux ◽

Cyril Melot ◽

...

Keyword(s):

Conflicts Of Interest ◽

Autologous Transplantation ◽

Allogeneic Transplantation ◽

Line Treatment ◽

Inclusion Criteria ◽

Front Line ◽

Entire Cohort ◽

Single Center Study ◽

First Relapse ◽

Time To Relapse

Abstract Abstract 4533 The aim of this single center study was to assess the outcome of pts with MM following the first relapse after autologous transplantation, according to whether or not a RICALLO was performed early in 2d response. Records of the patients were reviewed and the criteria for entering the study were: Symptomatic MM treated frontline with a program including single or double ASCT, relapse at any time following ASCT, response (CR, VGPR or PR) to a second line treatment. RICALLO was proposed to pts with no significant co-morbidities, having a suitable donor (either sibling or 10/10 MUD) and who gave their consent after precise information on the risk of the RICALLO. One hundred and seven pts treated between 01/2004 and 02/2011 fulfilling the inclusion criteria were identified. The initial treatment for relapse consisted of VD (37 pts), RD (29 pts), TD (36 pts), VTD (4 pts) or autologous SCT (1 pt). 22 pts received a RICALLO (allo group) while in 2d response, a median 7.7 months (2–36) after relapse. The RIC consisted of fludarabine plus either 2Gy ICT or busulfan and ATG (according to ongoing available protocols in the centre). The graft was PBSC from sibling (N: 8) or MUD (N: 14). 85 pts (CT group) received therapies according to ongoing protocols or available standard of cares. Following further relapses, 11 pts received a RICALLO while in ≥ 3d response in the CT group. The main characteristics of the patients in each group: age, MM prognostic factors at diagnosis, type of 1st line therapy (VAD or bortezomib containing regimens), single or double ASCT, time to relapse after ASCT and 2d line treatment were similar between the 2 groups. The response achieved with 2d line treatment was different between 2 groups (CR + VGPR/other: 8/14 and 7/76 in allo and CT group respectively, p= 0.01) The 3y OS from the time of relapse for the entire cohort was: 47% (CI95%, 41–53). It was of 45% (CI95% 34–56) and of 48% (CI95% 41–55) for the allo group and the CT group respectively (p= ns). The median time from 1st relapse to death was 31 mo in the entire cohort and 20 and 34 mo in the allo group and CT group respectively (p= ns). The causes of death were, relapse in 5 and 33 pts, or treatment toxicity in 8 and 3 pts in the allo group and CT group respectively. Three 3 y EFS (event = 2d relapse or death) was 16% (CI95%, 11–21) for the whole cohort and 16% (CI95%, 6–26) and 19% (CI95%, 13–25) for the allo group and CT group respectively (p= ns). Conclusion: In conclusion, we did not observe any difference in survival or PFS between allo-SCT and CT in patients at first relapse following an auto SCT. Disclosures: No relevant conflicts of interest to declare.

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A Better Mobilization Regimen for Newly Diagnosed Multiple Myeloma Patients,

Blood ◽

10.1182/blood.v118.21.4051.4051 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4051-4051

Author(s):

Ahmed Y Abuabdou ◽

Eric R Rosenbaum ◽

Saad Usmani ◽

Bart Barlogie ◽

Michele Cottler-Fox

Keyword(s):

Multiple Myeloma ◽

Conflicts Of Interest ◽

Optimal Number ◽

P Value ◽

Newly Diagnosed ◽

The Poor ◽

Cd34 Cells ◽

Significant Difference ◽

Minimum Number ◽

Poor Mobilizer

Abstract Abstract 4051 Introduction: What constitutes an acceptable mobilization regimen for collecting CD34+ cells depends on whether the goal of collection is to obtain a minimum number versus optimal number of cells. When treating patients with high-risk myeloma it may be important to obtain an optimal number. Here we compare retrospectively our earlier mobilization regimen, VTD-PACE, with MVTD-PACE in newly diagnosed, previously untreated multiple myeloma patients. Materials and Methods : We reviewed data for all patients who collected hematopoietic progenitor cells on Total Therapy protocols TT3a/TT3b with VTD-PACE (n=394) from February 2004 to September 2008 (138 females and 256 males, median age 59y; range 31–75), and on TT4/TT5 with MVTD-PACE (n=188) from August 2008 to May 2011 (78 females and 110 males, median age 61y, range 30–76). Based on their predicted first day collection with a large volume leukapheresis (30L processed), using our center's predictive formula (Blood 2010; 116(21):1182a), patients were stratified into 4 mobilizer types: poor (<2×106 CD34+ cells/kg), intermediate (≥2 to 10×106), good (>10 to 20×106) and excellent (>20×106). Variables examined included number of CD34+ cells/μl blood on day 1 and day 2 of collection (we have a minimum 2 day collection requirement), number of collection days to reach our minimum goal of 20×106 CD34+ cells/kg, and total CD34+ cells/kg collected for both chemotherapy groups. Variables for both groups stratified by mobilizer type were compared using two-tailed student's t-tests, except for the poor mobilizer group, where population size was too small for formal statistical analyses (VTD-PACE n=7, MVTD-PACE n=4), although averages were calculated. Results : There was no significant difference between VTD-PACE and MVTD-PACE for CD34+ cells/μl blood on day 1 of collection among the excellent [mean 368.9 (n=184) vs. 434.6 x106 (n=92); p-value 0.07], good [mean 138.6 (n=102) vs. 128.6 x106 (n=40); p-value 0.19], and intermediate [mean 60.1 (n=100) vs. 55.9 x106 (n=52); p-value 0.39] groups. A statistically significant difference between VTD-PACE and MVTD-PACE was found for CD34+ cells/μl blood on day 2 of collection for excellent mobilizers [mean 333.8 (n=184) vs. 460 ×106 (n=92); p-value <0.001], but not for the good [mean 165.7 (n=102) vs. 189.5×106 (n=40); p-value 0.21] and intermediate [mean 80.1 (n=101) vs. 102.3 ×106 (n=52); p-value 0.07] groups. When CD34+ cell/kg collection totals with VTD-PACE and MVTD-PACE were compared, a significant difference was seen for the intermediate mobilizer group only [mean 23.6 (n=101) vs. 26.3 ×106 (n=52); p-value 0.03]. For the poor mobilizer group, VTD-PACE had an average CD34+ cells/μl blood of 13.5×106 for day 1 of collection and 17.0 ×106 for day 2, with a total of 14.5×106 CD34+cells/kg collected; while MVTD-PACE had an average of 13.2×106 CD34+ cells/μl blood for day 1 of collection, 24.9×106 for day 2, with a total of 24.2×106CD34+ cells/kg collected. The number of collection days was similar between VTD-PACE and MVTD-PACE in the excellent mobilization group (2 days), but was slightly more for VTD-PACE compared to MVTD-PACE for the good (2.1 vs. 2 days), intermediate (3.2 vs. 2.9 days), and poor (6.1 vs. 5.8 days) groups. Conclusion : Both regimens allow more than minimum collections, but MVTD-PACE provides a higher peak number of CD34+ cells/μl blood, resulting in a slightly lower mean number of days of collection than VTD-PACE to reach an optimal collection. Disclosures: No relevant conflicts of interest to declare.

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Use of Plerixafor in Predicted and Proven Poor Mobilizer (according to GITMO criteria). Experience of Policlinico Universitario Tor Vergata

Blood ◽

10.1182/blood.v120.21.4415.4415 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4415-4415

Author(s):

Massimiliano Postorino ◽

Alessandro Lanti ◽

Eleonora Fiorelli ◽

Angelo Salvatore Ferraro ◽

Oana Marilena Chiru ◽

...

Keyword(s):

Side Effects ◽

Conflicts Of Interest ◽

Minimum Requirement ◽

Correct Definition ◽

Cd34 Cells ◽

Minimum Number ◽

Poor Mobilizer ◽

Operational Criteria ◽

Definition Of ◽

To Receive

Abstract Abstract 4415 BACKGROUND. Autologous stem cell transplantation (ASCT) of PBSCs has become a widely applied treatment for Multiple Mieloma (MM), non- Hodgking's lymphoma (NHL) and Hodgking's lymphoma (HL). Successful engraftment correlates with the number of CD34 hemopoietic progenitors cells infused. However, a part of MM or lymphoma patients (5% to 40%) fail to mobilize adequate numbers of PBSCs and thus cannot undergo to ASCT. The success of PBSCs mobilization is usually assessed by the total number of CD34+ stem cells collected, with a cutoff of 2.0–2.5 ×106 CD34+ cells/kg recipient body weight being considered as a minimum requirement for transplant. Poor mobilization of PBSCs is a major limitation to ASCT. Recently GITMO Working Group worked to define operational criteria for the identification/prediction of the poor mobilizer (PM) patients (Olivieri et al. 2011). Plerixafor, a CXCR4 chemochine antagonist, has been showed to improve significantly PBSC mobilization in PM patients. We present our experience using Plerixafor in PM patients classified according to GITMO criteria. METHODS. Between September 2009 and June 2012, a total of 17 patients (9F-8M) were enrolled. The diagnosis were: 10 MM (5F-5M), 1HL (1M), 6 NHL (4F-2M). The median age was 57 (range 15–66). 7 patients (3MM, 4NHL) were defined “Proven PM” and 10 patients (7MM, 2NHL, 1HL) “Predicted PM” according to GITMO criteria. The mobilization protocol included G-CSF, administered at a dose of 10μg/kg daily on 4 consecutive days. In the evening of the fourth day, patients received subcutaneous plerixafor at a dose of 0,24 mg/kg. Apheresis was initiated on the fifth day, 10–12 h after plerixafor and 1 h after G-CSF administration. Apheresis and daily administration of G-CSF and plerixafor continued until the patient collected enough CD34+ cells for auto- HSCT (> 2 ×106/kg; max 7 plerixafor injections if required). PBSC collection was initiated if peripheral CD34+ cells count was >10μl. A successful mobilization was defined as a total yeld of > 2×106/kg. RESULTS. 13 patients (76,5%) collected the minimum number of CD34 cells > 2×106/kg. The diagnosis were: 8MM, 1HL,1 NHL. 7 patients (2NHL; 4 MM; 1 LH; 7 predicted) were able to collect > 5×106/Kg. Only 4 patients (3 MM; 1 LNH; 4 proven) failed the mobilization because the numbers of cells CD34 were < 10μL and these patients did not undergo to apheresis procedures. The collection target of 2×106/Kg was reached in a median of 2 apheresis session (range 1–3). The technical characteristics of the procedures were (median value): blood volume processed 12 L (range 9–14), total CD34+/Kg collected 3,06 × 106(range 2,21-8,62), procedure efficiency 47,5% (range 35,3–79), duration of the procedure 261 minutes (range 210–309). Plerixafor was well tolerated and mild side effects were: reactions in the injection site, gastrointestinal disturbs, muscle pain. During administration of plerixafor we did not observe any significant laboratory abnormalities of liver or renal function. CONCLUSION. Unsuccessful mobilization represents an important limitation to ASCT in lymphoma and MM. In our experience plerixafor allowed to collect an appropriate amount of CD34 also in patients defined “proven PM” significantly reducing the percentage of patients that could not undergo ASCT (target value obtained in 43% of “proven PM”). Confirming the recent literature plerixafor is well tolerated with minimal side effects. We retrospectively applied GITMO criteria for PM patients and our experience, although limited, confirm that the use of a correct definition of PM allows the appropriate use of new mobilizing agents like plerixafor increasing significantly the therapeutic options also in patients who had no possibilities to receive an ASCT with the traditional mobilizing therapy. Disclosures: No relevant conflicts of interest to declare.

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Rituximab plus gemcitabine, ifosfamide, oxaliplatin (R-GIFOX) as salvage therapy for recurrent Hodgkin lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.8579 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 8579-8579

Author(s):

G. Corazzelli ◽

F. Frigeri ◽

G. Marcacci ◽

G. Capobianco ◽

M. Arcamone ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Therapeutic Potential ◽

Prognostic Score ◽

Autologous Transplantation ◽

Disease Free Survival ◽

Dose Intensity ◽

High Dose ◽

Free Survival ◽

Safe Delivery ◽

Cd34 Cells

8579 Background: Gemcitabine (G), ifosfamide (Ifo), oxaliplatin (Ox) and rituximab (R) have been accounted of cross-synergy in preclinical and early clinical studies in Hodgkin lymphoma (HL). We assessed activity, toxicity and stem cells (SCs) mobilizing capacity of a bi-weekly salvage combination with these agents in HL recurring after conventional or high dose therapy (HDT). Methods: Patients were scheduled to receive 3 R-GIFOX courses followed by SCs mobilization and HDT if elegible for autologous transplantation (ASCT) or 3 more courses if not. R-GIFOX consisted of R 375 mg/m2 D1, G 1000 mg/m2 D2, Ox 130 mg/m2 D3 and Ifo 5 g/m2 D3, as a 24-h single infusion, G-CSF 5 mcg/kg/d DD 7–11 (10 mcg/kg/d, 3rd course until SCs mobilization). Results: Twenty-one patients (median age 33 yrs, r 22–64) with relapsed (n = 16) [post-ASCT (n=6), <12 mo.s (n=7), > 12 mo.s (n=3)] or primary progressive (n = 5) HL, were prospectively accrued. Ten patients (48%) had received ≥ 2 previous CHT lines and 15 (78%) had GHLSG recurring HL prognostic score ≥ 2. Eighty-three total courses were delivered (median 3, r 3–6). CTCAE v3.0 G4 thrombocytopenia occurred in 18% of courses, G4 infection in 11%. Ifosfamide was withdrawn at the 4th course in 2 patients, both aged 64 yrs, due to tachyarrhythmia and encephalopathy. Actual dose intensity of the first 3 courses was 82%, 86%, 92 % for G, Ifo and Ox, respectively. The overall response according to FDG-PET/IWC criteria after 3 courses was 86%, with 2 partial and 16 complete responses (CRs) (76%; CR=10, CRu=6). Four CRs were achieved among the 6 patients with post-ASCT relapses. Eight of 14 eligible patients had effective CD34+ cells harvest [median 4,35 × 106/kg (r 2,91–11.45)] and proceeded to subsequent ASCT. Five ’bad mobilizers’ had previously undergone radiation therapy (n=3) and radioimmunotherapy (n=2). At 42 mo.s. Failure Free Survival was 57%. At a median f.u. of 12 mo.s for CRs, Disease Free Survival was 79% in patients eligible for ASCT and 41% in those unfit treated with additional R-GIFOX. Conclusions: R-GIFOX retains an attractive therapeutic potential in recurring HL, enabling pre-ABMT cytoreduction and mobilization, and also a safe delivery of a full salvage program to patients unfit for HDT. No significant financial relationships to disclose.

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Sequential Allogeneic Transplantation for Multiple Myeloma Patient in Early Relapse Post-Autograft

Blood ◽

10.1182/blood.v128.22.5768.5768 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5768-5768

Author(s):

Amandine Charbonnier ◽

Berengere Gruson ◽

Delphine Lebon ◽

Marie Beaumont ◽

Lavinia Merlusca ◽

...

Keyword(s):

Multiple Myeloma ◽

Acute Gvhd ◽

Conflicts Of Interest ◽

Chronic Gvhd ◽

Autologous Transplantation ◽

Young Patients ◽

High Morbidity ◽

Multiple Myeloma Patient ◽

Disease Evolution ◽

Early Relapse

Abstract Multiple myeloma (MM) remains mostly incurable despite novel therapeutic approaches. Allogeneic stem cell transplantation (ASCT) in MM could be the only curative treatment but is associated with a high morbidity and mortality, and relapses remain, mainly in high risk (17p deletion, (4;14) translocation, plasma cell leukemia, extramedullary disease or early relapse post-autograft). In refractory or poor risk cytogenetic acute myeloid leukemia (AML), sequential conditioning, followed by prophylactic immunomodulation with donor lymphocyte infusion (DLI), seems improve the outcome, compared to conventional ASCT regimens. Based on this sequential approach ASCT, we developed a sequential conditioning for MM, with a systematic immunomodulation strategy. The conditioning included melphalan 100mg/m² at day-10, followed by FB2 conditioning (fludarabine 30mg/m²/d day-6, -5,-4, -3, -2, busulphan 3.2mg/kg/d day-5, -4 and horse antithymoglobulin 2.5mg/kg/d day-3, -2). Prophylaxis of GVHD included cyclosporine and methotrexate according to ABO compatibility. This schema was proposed for young patients with early relapse after autograft (<1 year). The aim of the study was to evaluate feasibility and safety. In the absence of GVHD, 2 cycles of bortezomib (1,3mg/m² day 1, 4, 8, 11) without steroids followed by 3 escalated doses of DLI. Four patients received this sequential conditioning. All were low risk cytogenetic but were in early relapse post-autograft. Patients' characteristics are shown in table1. One patient received 2 autologous transplantation (patient 3). They received 2 or 3 lines of combination chemotherapy before allograft including: bortezomib (n=4), lenalidomide (n=4), pomalidomide (n=1). All of them were in partial response at time of ASCT. All patients were grafted with peripheral blood stem cells (median dose = 8 CD34+/kg [5.44-8.15]). Only one patient received methotrexate in addition to cyclosporine for GVH prophylaxis for ABO minor incompatibility. Two patients presented grade 3-4 acute GVHD: 1 was steroid-resistant and responded secondary to ruxolitinib, but unfortunately he died of septic shock. Patient 4 was in sCR with MRD negative 6 months post ASCT but currently presents signs of disease evolution without treatment criteria at 10 month. Two patients didn't presented GVHD and received prophylactic schedule with bortezomib followed by escalated doses of DLI. Three doses of DLI were planned: first dose=5x106 CD3+/kg, second dose=1x107CD3+/kg and third dose=5x107CD3+/kg. Only 2 doses were administrated because patients relapsed before the third dose. Patient 3 presented limited chronic GVHD (oral lichen) after DLI2 but relapsed 11 months post ASCT. Patient 1 relapsed at 10 months: they were retreated with pomalidomide and are now alive. In conclusion, sequential conditioning for young patients with MM in early relapse post-autograft is feasible. The addition of melphalan to the classical FB2 is safe without early toxicity (no mortality related to transplantation at day +100). 2 patients however presented severe acute GVHD. Despite the post ASCT immunomodulation, this procedure was not capable to control the disease. The optimization of conditioning procedure, the post-allograft immunomodulation and a maintenance therapy may provide a benefit to patients and, thus, requires further study. Table 1 Table 1. Disclosures No relevant conflicts of interest to declare.

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Impact of Early Immune Reconstitution after Haploidentical Stem Cell Transplantation with Post-Transplant Cyclophosphamide

Blood ◽

10.1182/blood-2018-99-119601 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2118-2118

Author(s):

Nieves Dorado ◽

Ana Pérez-Corral ◽

Mi Kwon ◽

Laura Solán ◽

Rebeca Bailén ◽

...

Keyword(s):

Nk Cells ◽

Lymphocyte Count ◽

Immune Reconstitution ◽

Conflicts Of Interest ◽

Conditioning Regimen ◽

Prognostic Significance ◽

Disease Free Survival ◽

Haploidentical Transplantation ◽

The Impact

Abstract Introduction: Immune reconstitution (IR) has a significant impact in HSCT outcome with a role against opportunistic infections and in disease control. In the setting of unmanipulated haploidentical transplantation (Haplo-HSCT), some groups have identified the absolute leukocyte count on day +30 (ALC30) as an independent prognostic factor in terms of overall survival (OS), disease free survival (DFS) and infection related mortality (IM). The aim of this study was to evaluate the impact of early IR on different HSCT outcomes in patients who underwent Haplo-HSCT with postransplant cyclophosphamide (PTCy) at our institution. Patients and methods: Eighty-eight patients received a Haplo-HSCT from 2011 to 2016. Thirty-six percent of the patients received myeloablative conditioning regimen and 64% received reduced intensity regimen. Graft-versus-host disease (GVHD) prophylaxis was based on PTCy, cyclosporine and mycophenolate mofetil. Early IR was assessed through the analysis of different lymphocyte subpopulations at days +30 and +90 after transplantation, including ALC30 (cellular analyzer DXH, Beckman Coulter®); CD3+ lymphocyte count and their different subpopulations (CD4+ and CD8+ lymphocytes, naive and memory T cells) and NK cells count. Lymphocytes subpopulations were determined by multiparametric flow cytometry (FC500 and Navios, Beckman Coulter®). ROC curves were used to determine the optimal cut-off values for each of the studied variables. Results: Eighty-one patients were studied, excluding 7 who died before day +30. Median follow-up was 26 months (10-43). Patient´s characteristics are shown in Table 1. CMV reactivation was documented in 76% (62) of the patients, 4% (3) developed a proven invasive fungal infection, and 31% (25) presented hemorrhagic cystitis. Median OS and DFS were 26 months (10-43) and 24 months (9-39), respectively. IM rate and NRM rate were 10% and 24%, respectively, at the end of follow up. Median lymphocyte populations counts at day +30 are shown in Table2. ALC30 below 100 cells/uL (p= 0.027) and CD4+ naïve lymphocytes below 12 cells/uL (p=0.033) (both corresponding to the 25 percentile) were associated with lower OS compared to patients with higher counts at day +30 (Figure 1). Patients with ALC30 lower than 300 cells/uL (p=0.026) showed significantly higher NRM; CD8+ count lower than 20 cells/uL (p=0.022) also showed higher NRM. NK cells counts at day +30 lower than 14 cells/uL (p=0.014), near to percentile 25, predicted higher IM (62.5% vs 37.5%). We did not identify any lymphocyte subpopulation that could predict DFS. Patients with acute GVHD grades II-IV showed values of ALC30 lower than 200 cells/uL (p=0.051), although non-statistically significant. No relationship was found between lymphocytes subpopulations at day +90 and HaploSCT outcomes. Conclusions: Our study supports the prognostic significance of early IR after unmanipulated haploidentical transplantation with PTCy, as previously described by other groups. ALC30, CD4+ naïve lymphocytes, and CD8+ lymphocyte count at day +30 may be good early predictors for OS and NRM in this setting. On the other hand, low NK cells counts (lower than percentile 25) predicted higher IM. Patients with very low lymphocyte counts should be monitored closely as they are at high risk for infectious complications, NRM and OS. Disclosures No relevant conflicts of interest to declare.

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Myeloablative Conditioning of Patients with Myelofibrosis with Myeloid Metaplasia Using i.v. Treosulfan and Autologous Peripheral Blood Progenitor Cell Transplantation (PBPCT) with High Doses of CD34+ Cells Results in Hematologic Responses - 32 Months Follow-Up of Three Patients and Short-Term Results of a New Study.

Blood ◽

10.1182/blood.v106.11.5515.5515 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5515-5515

Author(s):

Stefan Fruehauf ◽

Eike C. Buss ◽

Julian Toplay ◽

Hans H. Kreipe ◽

Anthony D. Ho

Keyword(s):

Multicenter Study ◽

Autologous Transplantation ◽

Conditioning Regimen ◽

Allogeneic Transplantation ◽

High Dose ◽

Post Transplantation ◽

Myeloid Metaplasia ◽

Cd34 Cells ◽

Myelofibrosis With Myeloid Metaplasia

Abstract Myelofibrosis with myeloid metaplasia (MMM) is a chronic myeloproliferative disorder. Myeloablation with high-dose treosulfan and autologous PBPCT provides a palliative approach. A minimum of 5 x 106 CD34+ cells/kg was collected in all patients after G-CSF-priming (16 μg/kg/d for 4 days). Myeloablation consisted of treosulfan (total dose 42 g/m2). To date we have transplanted 3 patients, all female on an individual basis. We observed a prolonged time to reconstitution of leucocytes > 1/nl post transplantation of 28 days (#1, #2) and 38 days (#3). The observation period post transplantation is 32 months now. Patient #1, who required erythrocyte transfusions twice weekly pretransplant received her last erythrocyte transfusion on day 56; her last Hb-value is 9.5 g/dl. The second patient (#2) recovered to platelet counts higher than pre transplantation (58/nl) at 3 months (143/nl) and had 125/nl at last follow-up. Pat. #3 showed a marked reduction of max. spleen size and a rise in Hb from 9 g/dl to 12 g/dl after 12 months, the last Hb value at 26 months was 7.6 g/dl and she received about 3 erythrocyte transfusions per month again. She then underwent allogeneic transplantation from her sister and is currently alive and well. Three male patients were treated in a new one-armed, multicenter study applying the aforementioned protocol. In two patients we observed again a prolonged reconstitution period of 28 (S1) and 44 (S2) days. In one patient (S1) leukocytosis and thrombocytosis resolved while transfusion dependent anemia persisted. In the second patient (S2) transfusion dependent anemia persisted. He received a backup transplantation but still remains transfusion-dependent. Patient S3 had a critical thrombocytopenia of 16/nl before transplantation and proved to be refractory to thrombocyte transfusions post-transplantation. He developed cerebral hemorrhage and died. The conditioning regimen was well tolerated and despite the prolonged aplasia period neutropenic fever was rare (median 1 day, range 0–6 days). The overall response rate was 60%, the mortality rate was 17% which is both compatible with previous data of autologous transplantation in MMM patients undergoing busulfan conditioning. This multicenter study is continuing to recruit patients (http://leukaemie.krebsinfo.de/kn_home/Studien/studie_101.html).

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Outcome of BEAM-Autologous and BEAM-Alemtuzumab Allogeneic Transplantation in Relapsed Advanced Stage Follicular Lymphoma

Blood ◽

10.1182/blood.v120.21.2022.2022 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2022-2022

Author(s):

Victor Noriega ◽

Anjum Bashir Khan ◽

Stephen Devereux ◽

Robert E. Marcus ◽

Michelle Kenyon ◽

...

Keyword(s):

Overall Survival ◽

Follicular Lymphoma ◽

Conflicts Of Interest ◽

Chronic Gvhd ◽

Disease Free Survival ◽

Allogeneic Transplantation ◽

High Grade ◽

Advanced Stage

Abstract Abstract 2022 Introduction: Follicular Lymphoma is the most common indolent lymphoma, characterized by an indolent course, multiple recurrence, responses to chemotherapy, risk of transformation into a high grade lymphoma and with a median overall survival of 10–12 years. Transplantation (autologous and allogeneic) has improved the overall outcome of this disease, however a continuous pattern of relapse is observed essentially in the autologous setting. Allogeneic transplant has shown encouraging results in terms of long term overall survival (OS) and disease free survival (DFS), with acceptable transplant related mortality (TRM) and with significantly lower relapse rate. Objective: To analyse retrospectively the outcome of relapsed follicular lymphoma patients who received BCNU (carmustine), cytarabine, etoposide, melphalan-alemtuzumab allogeneic HSCT (BEAM-C allo) or BEAM-autologous HSCT (BEAM-auto). Results: The study includes 74 consecutive patients with relapsed advanced stage follicular lymphoma who received BEAM-C allo (n=38) and BEAM-auto (n=36) between 1992 and 2010. Patients characteristics are summarized in Table 1. Median follow-up of surviving patients was 6.1 years. Patients undergoing allo transplants were younger than those who unbderwent and autologous procedure (50 vs 54 years, p=0.018). 1y and 5y TRM was higher in the allo transplant group (27% and 27% vs 6% and 6%; p=0,011). The Cumulative incidence of relapse (CIR) was lower in the allo at 1, 2 and 5 years (11%, 14% and 18% vs 28%, 49% and 60%, p=0,000). Significant differences were not observed in 1, 2 and 5 years OS between allo and auto transplant groups (74%, 74% and 69% vs 85%, 69% and 51%; p=0,217), but we found a strong trend in DFS difference between both groups at 1, 2 and 5 years (65%, 61% and 58% vs 69%, 43% and 33%; p=0.089) observing a plateau around 60% after 2 years in the allograft group. The rate of graft versus host disease (GvHD) was low with 14% acute GvHD (2.6% grade 3–4 GvHD) and 28% chronic GvHD (10% of extensive chronic GvHD). Analysis of the whole cohort (n=74) showed that patients in CR before transplant (n=28) had better 1, 2 and 5 years DFS following a allotransplant (69%, 69% and 69% vs 79%, 36% and 18%; p=0.012). These differences did not affect the 1, 2 and 5 years OS (76%, 76% and 76% vs 93%, 76% and 56%; p=0,214). TRM for the allo transplant group was 24% and 0% R in the auto (p=0,064) in patients when achieved CR before transplant. There were no difference in OS (p=0,785) and DFS (p=0,954) between allo or auto patients in partial response (PR) before transplant. A subgroup analysis of patients with high grade transformation before transplant did not show any differences in OS (p=0,823) or EFS (p=0,526).between allo and auto groups. Conclusions: Long term follow-up of Follicular Lymphoma patients has shown a continuous pattern of relapse when patients receive an autologous transplant, after 5 years. whereas patients undergoing allo transplant, despite a higher mortality, have a 5 year OS and DFS of 60% with a plateau been achieved in both curves after 2 years suggesting that these patients may be cured. Prospective randomised studies are still required to answer the the role of these two approaches in follicular Lymphoma. Disclosures: No relevant conflicts of interest to declare.

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Minimal Residual Disease In Adult AML

Blood ◽

10.1182/blood.v122.21.4969.4969 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4969-4969

Author(s):

Ihab A. Eldessouki ◽

Ola Khorshid ◽

Eman Kandeel ◽

Nasr Lahloubi

Keyword(s):

Treatment Response ◽

Minimal Residual Disease ◽

Conflicts Of Interest ◽

Residual Disease ◽

Prognostic Significance ◽

Disease Free Survival ◽

Tumor Burden ◽

Multiparametric Flow Cytometry ◽

Post Induction ◽

Minimal Residual

Abstract Background The achievement of complete hematologic remission (CR) is used as predictor for treatment response in patients with myeloid leukemia (AML).However <5% blasts in the bone marrow does not reflect the presence of tumor burden precisely. Minimal residual disease (MRD) in the first complete remission (CR1) may play a critical rule in assessment of treatment response and prediction of subsequent relapse. Patients and Methods Leukemia associated immunophenotyping (LAIP) for 73 patients with denovo AML monitored at diagnosis , day 14 and day28 post-induction by multiparametric flow cytometry (MFC). Results CR achieved in 60(82%) patients and 13(18%) patients did not. Among the 60(80%) patients who achieved CR 9 (15%) were MRD negative and 51(85%) were MRD positive at day14. Significant association between MRD detection and disease free survival (DFS) using 0.01% cut off value (P=.015). Day 28 post induction show highly significant association between MRD and DFS using 0.01% cut off value (P=0.001) as 38(63%) patients were MRD negative and (27%) were positive. Significant association between MRD detection and overall survival (50 month) at day 14 and day 28 (P=0.02, P=0.001) respectively using cut off value 0.01%. MRD was positive in 63(86%) at day 14 and (37%) at day 28. Conclusion MRD detection at day28 and d14 at the end of induction in patients in CR may have a prognostic significance on clinical outcome and may thus be a useful marker for risk stratification. Disclosures: No relevant conflicts of interest to declare.

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