Peripheral Blood Stem Cell Mobilization In Hiv Positive Patients with Lymphoma Candidates to Autologous Transplantation: Predictive Factors Analysis for Failure or Suboptimal Stem Cell Collection

Abstract Abstract 2250 Background: Autologous stem cell (SC) transplantation (ASCT) is a potentially curative treatment for several hematologic malignancies and has been demostrated feasible and effective in HIV-related lymphoma (ARL). Peripheral blood SC collection could represent a major issue in the use of ASCT in HIV infected patients (pts). Aim: To evaluate the feasibility and efficacy of SC mobilization in HIV positive (pos) pts with lymphoma and identify factors influencing harvest results. Potential “ongoing” predictors of collection were also assessed. Patients and Methods: We retrospectively analysed 98 consecutive pts with ARL, candidates to ASCT, who underwent SC mobilization at 3 Italian and 2 Spanish centers from 2000 to 2010. A collection less than 2×106 CD34+ cells/kg was defined as “mobilization failure”, between 2–5 as “suboptimal collection” and more than 5 as “good collection”. Several parameters were evaluated for correlation with outcome: age, sex, lymphoma histopathology, disease status, WBC and Plt count at start of mobilization, type of mobilizing therapy, marrow disease, previous mobilization failure, n° of previous chemotherapy (CT) lines, months from first detection of HIV positivity, CD4 count and HIV-viremia. Moreover, circulating CD34+ and WBC count on the first day of CD34+ monitoring and their ratio (SC ratio = CD34/WBC) were assessed as “ongoing” outcome predictors. Results: A total of 127 attempts of SC harvest in 98 pts were analysed. Median age was 41.5 ys (28-65). Lymphoma diagnosis was DLBCL in 42% of cases, Burkitt 10%, plasmablastic 10%, HL 31%, anaplastic 5%, follicular lymphoma 1% and PEL 1%. Disease status was complete remission in 36%, chemosensitive disease in 53% and refractory disease in 10% of cases. In 3 cases bone marrow was involved and mobilizations failed. In 18% of cases pts received mobilizing therapy after 1 previous CT line, in 67% after 2 and in 16% after 3 or more. All pts but 2 were on antiretroviral therapy. Median CD4 count was 231/mcl (50-1146) and HIV-viremia was detectable in 22%. Median time from first HIV detection was 79.5 ms (3-295). In 24% of cases G-CSF alone (10-20 mcg/Kg) was used as mobilizing treatment, while CT + G-CSF (5-10 mcg/Kg) in 76%, including single-agent Cyclophosphamide (CTX) 1.5 gr/ms (13%), CTX >3 gr/ms (27%), platinum containing regimens (20%), ifosfamide containing regimens (11%) and others (5%). Mobilization failure occurred in 40% of procedures, a collection between 2–5 × 10^6 CD34/Kg in 24% and > 5 in 35%. Finally, of 98 pts who underwent SC mobilization, 22% failed to collect enough cell to perform ASCT, 12 pts even after repeated attempts, 33% had a suboptimal and 45% a good collection (4 and 5 pts respectively after repeated mobilizations). At univariate analysis failure was significantly associated with refractory disease, Plt < 150.000/cmm, CTX 1.5 gr/ms as mobilizing treatment, previous mobilization failure and circulating CD34+ cell < 7.4/mcl on the first day of monitoring; whereas CTX > 3 gr/ms, CD4 count and SC ratio > 0.002 were associated with a reduced risk of failure. In multivariate analysis refractory disease (p<0.0001) and CTX 1.5 gr/ms (p=0.003) were indipendent predictors for failure and SC ratio > 0.002 (p<0.0001) a protective factor. A good collection was predicted at univariate analysis by Plt and CD4 count, age, months from first HIV detection, CT + G-CSF as mobilizing therapy, CTX > 3 gr/ms, WBC count and circulating CD34+ cells >29,7/mcl at the first day of monitoring and SC ratio > 0,002, whereas G-CSF alone and previous mobilization failure were negative predictive factors. Multivariate analysis confirmed CTX > 3 (p<0.0001), CD34+ cells > 29,7 (p=0.0003) and SC ratio > 0,002 (0.0036) as indipendent factors for good collection. Conclusions: In this series of 98 ARL and 127 SC mobilization attempts, a substantial number of pts failed SC harvest (22%) whereas 33% had a suboptimal and 45% a good collection. Lymphoma status and mobilizing treatment seems the strongest predictors for outcome, with refractory disease and low CTX dose (1.5 gr/ms) significantly associated with failure and CTX > 3 gr/ms predictor for good collection. A high ratio between circulating CD34+ cells and WBC on the planned day of first apheresis might represent a useful “ongoing” parameter to predict the outcome. These data might help to decide the mobilizing strategy in ARL and could provide the framework to rationally explore the use of new mobilizing agents Disclosures: No relevant conflicts of interest to declare.

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Peripheral Stem Cell Mobilization with Chemotherapy + G-CSF Priming in a Large Series of Patients with Lymphoma Candidates to Autologous Transplantation. An Analysis of Baseline and Ongoing Predictors of Failure or Suboptimal Stem Cell Collection.

Blood ◽

10.1182/blood.v114.22.2149.2149 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2149-2149

Author(s):

Enrico Morello ◽

Camillo Almici ◽

Luca Arcaini ◽

Liliana Baushi ◽

Barbara Botto ◽

...

Keyword(s):

Multivariate Analysis ◽

Stem Cell ◽

Predictive Factors ◽

Alkylating Agents ◽

Univariate Analysis ◽

Single Agent ◽

Disease Status ◽

Large Series ◽

Increased Risk ◽

Cd34 Cells

Abstract Abstract 2149 Poster Board II-126 Background Autologous stem cell transplantation (ASCT) is a potentially curative treatment for lymphoma. Adequate stem cell (SC) collection is possible in the majority of cases but poor mobilization remains a major issue in some patients (pts). New agents were recently developed which may improve the rate of SC mobilization. Aims A retrospective analysis was conducted on a large series of lymphoma pts candidates to ASCT in order to identify factors influencing SC mobilization outcome. Potential early markers of poor mobilization were also evaluated. Patients and methods A total of 415 attempts of PBSC collection consecutively performed at 7 Italian centres in 388 pts affected by lymphoma were analyzed. Their median age was 52. A collection of less than 2×106 CD34+ cells/kg was defined as “mobilization failure” and of more than 5×106 CD34+ cells/kg as “good mobilization”. The following parameters were analysed for correlation with mobilization outcome: lymphoma diagnosis, disease status at mobilization, type of mobilizing chemotherapy, bone marrow infiltration at collection, n° of previous lines of therapy, prior use of fludarabine, alkylating agents or radiotherapy. The ratio between circulating CD34+cells/nL and total WBC/μL on the first day of CD34+ count (SCratio) was also analysed, trying to predict mobilization failure. Both univariate and multivariate statistical analyses were performed with SPSS package 13.0. Results Lymphoma diagnosis was diffuse large B cell/Burkitt in 38%, follicular in 10%, mantle in 13%, Hodgkin in 26%, T or NK/T in 6%, and other in 7% of cases. Disease status at apheresis was CR in 25%, chemosensitive in 49% and refractory in 26%. Mobilization was attempted during first-line therapy in 14%, in 37% during second-line and in 26% at third- or subsequent lines of therapy. Fludarabine, alkylating agents and extended-fields radiotherapy had been used prior to mobilization in 5%, 73% and 13% of cases respectively. Marrow infiltration by lymphoma was present in 17,7% and 7,7% of patients had failed a prior mobilization attempt. In 99% of cases (411/415) mobilizing therapy included chemotherapy and G-CSF. Two pts received AMD3100 and 2 G-CSF. Several chemotherapy programs were used for mobilization. For analysis purposes they were grouped as follows: single-agent cyclophosphamide (CTX) in 62 (15,1%); high-dose cytarabine, either single agent or in combination (HD-ARAC) in 143 (34,8%), etoposide-containing regimens in 119 (30,0%), and platinum containing regimens in 108 cases (26,3%). Mobilization failure occurred in 14% (59/415) whereas a good mobilization was obtained in 72% of cases. At univariate analysis mobilization failure was significantly associated with the use of single-agent CTX as mobilizer (p=0.000), with the n° of prior lines of treatment (p=0.006) and with failure of a previous mobilization attempt (p=0.000) whereas a diagnosis of follicular lymphoma (FL) was associated with a reduced risk of mobilization failure (p=0.007). Multivariate analysis confirmed FL as protective factor for mobilization failure (p=0.008) and single agent CTX and a higher n° of prior treatment lines as negative predictive factors (p=0.000 and 0.033 respectively). A “good mobilization” was significantly predicted at univariate analysis by HD-ARAC use as mobilizer (p=0,004) whereas single-agent CTX (p=0.000), n° of prior lines of therapy (p=0.005), prior fludarabine (p=0.035) or alkylating agents (p=0.003) were adverse predictors. Multivariate analysis confirmed HD-ARAC as independent predictive factor for good mobilization (p=0.031) and single-agent CTX and n° of prior lines of therapy as independent negative predictive factors (p=0.000 and 0.003 respectively). A SCratio of less than 10 on the first day of CD34+ count was associated with an increased risk of poor mobilization (p=0.000 risk estimate 0.638). Conclusions In this large series of pts with lymphoma the standard policy of SC mobilization was the use of chemotherapy + G-CSF. Nevertheless collection failed in a significant proportion of cases (14 %) and only 72% of cases reached an optimal SC collection. Predictive factors for mobilization outcome included disease and treatment history, type of lymphoma and type of mobilizing chemotherapy. These data provide the framework to rationally explore the use of new mobilizing agents in patients with lymphoma undergoing SC mobilization with chemotherapy and G-CSF. Disclosures: No relevant conflicts of interest to declare.

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Improved Outcome with Busulfan, Melphalan, and Thiotepa Conditioning (BuMelTt) in Autologous Hematopoietic Stem Cell Transplantation for Relapsed/Refractory Hodgkin Lymphoma

Blood ◽

10.1182/blood.v118.21.3110.3110 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3110-3110

Author(s):

Tarunpreet Bains ◽

Andy I Chen ◽

Andrew Lemieux ◽

Brandon Hayes-Lattin ◽

Jose F. Leis ◽

...

Keyword(s):

Multivariate Analysis ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Hodgkin Lymphoma ◽

Cell Transplantation ◽

Univariate Analysis ◽

Disease Status ◽

Significant Difference ◽

Conditioning Regimens ◽

Refractory Hodgkin Lymphoma

Abstract Abstract 3110 High-dose therapy followed by autologous stem cell transplantation (ASCT) is standard therapy for patients with relapsed or refractory Hodgkin Lymphoma (HL), although the optimal conditioning regimen remains uncertain. The three drug alkylating agent regimen, BuMelTt, has been established as our institutional regimen. We performed a retrospective review of outcomes obtained with BuMelTt compared to those achieved with other standard conditioning regimens. 133 patients with relapsed/refractory HL who underwent ASCT between January 1990 and December 2009 were analyzed. 62 patients received BuMelTt and 71 patients received other standard preparative regimens (Standard) consisting of CBV (44), CyVp16TBI (20), BEAM (4), CyTBI (2), and Mel (1). The median follow-up (range) was 4.3 years (0.01–14.24) in BuMelTt and 3.9 years (0.07–20.21) in Standard. The two groups (BuMelTt vs Standard) were balanced for gender (65% male vs 65% male), median age (29 vs 33), median number of prior regimens (2 vs 2), and pre-transplant disease status. Disease status was categorized as PR2/CR2 (48% vs 42%), primary induction failure sensitive (16% vs 17%), and Other which included PIF-refractory, 1st relapse refractory, and greater than 1st relapse (35% vs 41%). The 5 year overall survival (OS) was superior for patient who received BuMelTt conditioning (74% vs 54%, p = 0.03). There was also a trend for improved 5 year event free survival (EFS) for BuMelTt at 56% vs 39% for Standard (p=0.07). Other risk factors for outcome after ASCT were also analyzed and included disease status, more than 2 chemotherapy regimens before ASCT, Karnofsky score < 90% at ASCT, time from diagnosis to ASCT < 12 months, prior extranodal involvement, and age > 40 years. By univariate analysis, >2 chemotherapy regimens before ASCT (HR 1.7, p=0.05) and disease status of Other (HR 2.8, p<0.01) were predictive for lower OS. There was a trend for influence on OS for BuMelTt (HR 0.6, p=0.07) and PIF-sensitive (HR 1.9, p=0.09). By multivariate analysis, disease status of PIF-sensitive or Other predicted worse outcomes for OS (HR 2.4 & 2.9, p 0.03 & <0.01, respectively), and there was still a trend for benefit with BuMelTt (HR 0.6, p=0.09), although >2 chemotherapy regimens lost significance (p=0.22). For EFS, disease status of PIF-sensitive or Other were prognostic in univariate analysis (HR 2.1 or 2.3, p=0.02 or <0.01, respectively), and there was a trend for improved EFS with BuMelTt (HR 0.66, p=0.08). In multivariate analysis, disease status of PIF-sensitive or Other remained prognostic (p=0.03 & 0.004, respectively), while BuMelTt was not significant (p=0.27). There was no significant difference in 100 day non-relapse related mortality for BuMelTt vs Standard conditioning (5% vs 3%, p=0.88). More patients developed NCI CTCAE grade 3/4 mucositis with BuMelTt than Standard (89% vs 61%, p<0.01), but fewer patients had bacteremia with BuMelTt than Standard (7% vs 23%, p=0.02). There was no difference in duration of hospitalization, episodes of febrile neutropenia, incidence of veno-occlusive disease, time to neutrophil engraftment, or time to platelet engraftment. Our results suggest that BuMelTt may improve OS and EFS compared to standard conditioning regimens with increased but manageable toxicity. A case matched control study is planned. Disclosures: No relevant conflicts of interest to declare.

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Poor Stem Cell Mobilization: incidence and Risk Factors

Blood ◽

10.1182/blood.v122.21.5439.5439 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5439-5439

Author(s):

Rui Bergantim ◽

Eliana Aguiar ◽

Teresa Garrido ◽

Rita Damas ◽

Abel Carreira ◽

...

Keyword(s):

Multivariate Analysis ◽

Stem Cell ◽

Predictive Factors ◽

Univariate Analysis ◽

Stem Cell Mobilization ◽

Cell Yield ◽

Hodgkin's Lymphoma ◽

Prior Use ◽

Cell Mobilization ◽

Number Of Cycles

Abstract Background and Aims High dose chemotherapy followed by autologous stem cell transplant (ASCT) is an effective treatment for many patients with haematological malignancies. Adequate stem cell mobilization (SCM) and collection are essential for a successful ASCT. Unfortunately, a small group of patients fail to mobilize sufficient stem cell for transplant. In order to explore factors influencing SCM we conducted a retrospective analysis on a large series of candidates for ASCT in a Portuguese transplantation center. Patients and Methods We analyzed 233 patients who underwent consecutively SCM from 2007 to 2012. Patients with CD34+ <10/μL in peripheral blood at maximum stimulation were considered non-mobilizers (NM) and patients that didn’t harvest the minimal count of 2×10^6 CD34+/kg at maximum number of aphaeresis cycles were considered poor mobilizers (PM). Patient diagnosis, sex, age, body weight, previous radiotherapy, number of cycles of previous chemotherapy, status disease at mobilization and premobilization platelet count, prior use of fludarabine or alkylating agents were analyzed for correlation with mobilization. Results Two patients received granulocyte colony-stimulating factor (G-CSF), all others received G-CSF plus chemotherapy (G+C) for the initial mobilization. 68 patients had non-Hodgkin’s lymphoma (NHL), 23 Hodgkin’s lymphoma (HL), 94 multiple myeloma (MM), 46 acute myeloid leukemia (AML) and 2 non-hematological malignancies (NHM). The median age was 54 years (min-max: 18-69) and 108 were females. A successful SCM was achieved in 217 patients (93.1%) and the NM ratio differed with respect to diagnosis (NHL: 11.7%, AML: 9.5%, HL: 9%, MM: 2.1%, NHM: 0%). At univariate analysis NM was significantly associated with the number of cycles of previous chemotherapy (p=0.003), status disease at mobilization (p=0.000) and prior use of fludarabine (p=0.013). Multivariate analysis confirmed the higher number of cycles of previous chemotherapy (p=0.002) and prior use of fludarabine (p=0.000) as negative predictive factors for SCM. For the 217 patients who underwent stem cell collection, 504aphaeresis were performed. Median number of aphaeresis necessary to harvest 2×10^6 CD34+/kg was 2 (min-max:1-6). Median CD34+/kg harvested was 4.6x10^6 (min-max:1.82-52.7), with 43.3% patients collecting 2x10^6 CD34+/kg in one aphaeresis. MM patients had the highest total CD34 cell yield (median 6.9x10^6 CD34+/kg, min-max: 2-52.7) and required less aphaeresis to collect 2×10^6 CD34+/kg. At univariate analysis diagnosis of MM (p=0.000), status disease at mobilization (p=0.007) and the number of cycles of previous chemotherapy (p=0.002) were significantly associated with PM. Multivariate analysis confirmed the diagnosis of MM (p=0.000) and the lower number of cycles of previous chemotherapy (p=0.002) as favorable predictive factors for the total CD34+ cell yield. Grade III or IV hematopoietic toxicity of chemotherapy had no significant effect on the SCM. Incidence of febrile neutropenia was similar in all patients without morbidity. There was no mortality associated with SCM. Conclusions G+C SCM appears to be safe in all patients without major toxicity or morbidity. Our results enhances the need for effective first-line mobilization agents in patients with higher number cycles of chemotherapy and use of fludarabine prior SCM; these patients probably would benefit for a early SCM in order to achieve a higher CD34+ cell yield. Disclosures: No relevant conflicts of interest to declare.

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The Influence of PET/Gallium (PET/Gal) Status and High-Dose Rituximab (HDR) in Patients with Aggressive, Large, B-Cell Lymphoma (LBCL) Receiving Autologous Stem Cell Transplants (ASCT).

Blood ◽

10.1182/blood.v108.11.3058.3058 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3058-3058 ◽

Cited By ~ 1

Author(s):

Amin M. Alousi ◽

Rima M. Saliba ◽

Grace-Julia Okoroji ◽

Chitra Hosing ◽

Barry I. Samuels ◽

...

Keyword(s):

Multivariate Analysis ◽

Stem Cell ◽

De Novo ◽

Univariate Analysis ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Disease Status ◽

High Dose ◽

Free Survival ◽

The Impact

Abstract Background: PET/Gal status has been reported to be an important predictor of outcome in patients with LBCL who receive an ASCT. Newer conditioning regimens which include high-dose rituximab (HDR) have been shown to improve results (Khouri, JCO, 2005). The impact of HDR on the outcome of patients based on PET/Gal status has not been determined. Methods: A retrospective review of patients with chemo-sensitive, LBCL who received an ASCT on a research protocol at MD Anderson between 1995 and 2005 was performed. Factors that were considered for outcome included: Age, IPI, # of prior chemotherapies, B2-microglobulin, disease status at transplant, HDR and PET/Gal status. In patients who received HDR, it was given with stem cell mobilization and then again on days +1 and +8 following transplant. Results: A total of 188 patients were identified. Median age was 49 years with 108 (57%) male patients. 147 patients (78%) had de novo LBCL and 41 (22%) had a LBCL of follicular origin (LBCL-F). 83 (39%) patients received HDR. At transplantation, 95 patients (50%) were in PR, 71 (38%) in CRU and 22 (12%) in CR. 142 (76%) patients were PET/Gal negative, 37 (20%) PET/Gal positive and 9 (4%) were unknown. Median follow-up was 47 months. On multivariate analysis, for patients with de novo LBCL, PET/Gal status and HDR were the only predictors for progression and progression free survival (PFS). Patients who were PET/Gal negative and those that received HDR had a hazard ratio (HR) of 0.3 (p<0.001) and 0.5 (p=0.02) for progression, respectively (see the table below for the cumulative incidence (CI) for progression and PFS at 54 months according to HDR and PET/Gal status for de novo LBCL undergoing ASCT). PET/Gal Status and HDR were also found to be predictive for patients with LBCL- F on univariate analysis, however due to the small numbers in this subset; multivariate analysis could not be performed. PFS at 54 months for patients with LBCL-F who were PET/Gal negative was 40% versus 17% in the PET/Gal positive group, (p=0.006). PFS for those LBCL-F patients who received HDR was 81% as compared to 23% for those who did not receive HDR, (p=0.007). Conclusions: The two most important predictors of outcome following ASCT are PET/Gal status and whether HDR was given with the transplant regimen. The addition of HDR to the transplant regimen decreases the risk for progression irrespective of PET/Gal status; however the improvement is more significant in patients with a negative PET/Gal scan. C.I. for progression and PFS at 54 months for de novo DLBCL PET/Gal Status HDR CI of Progression (%) Progression Free Survival Positive No 83 17 Positive Yes 54 45 Negative No 35 55 Negative Yes 22 75

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Allogeneic Stem Cell Transplantation in Hodgkin Lymphoma: The Timing of Relapse after Autologous Transplant and Primary Refractory Disease Do Not Impact the Survival Outcomes

Blood ◽

10.1182/blood.v126.23.2016.2016 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2016-2016

Author(s):

Francesco Spina ◽

Serena Camilla Dalto ◽

Simonetta Viviani ◽

Chiara De Philippis ◽

Anna Dodero ◽

...

Keyword(s):

Multivariate Analysis ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Disease Status ◽

Complete Response ◽

Salvage Treatment ◽

Refractory Disease ◽

Resistant Disease

Abstract The present study retrospectively analyzed a cohort of consecutive relapsed/refractory Hodgkin lymphoma (RR-HL) patients receiving allogeneic stem cell transplantation (alloSCT) in a single center with a thiotepa-based conditioning to understand whether the timing of relapse after autologous stem cell transplant (ASCT) or the primary refractory disease would change the survival. Of 247 patients with HL referred to our division from 2001 to 2014, 109 had RR-HL (64 primary refractory). After receiving salvage treatment, 62 patients (57%) underwent alloSCT with a thiotepa-based conditioning; 4 patients (4%) received fludarabine-melphalan conditioning in a phase II study, 43 patients (39%) did not receive alloSCT for progressive disease (31), advanced age (>65 years, 3 patients) or for achieving a complete response after a third-line chemotherapy consolidated by ASCT (9). This study analyzes the outcomes of the 62 consecutive patients allografted with thiotepa-based conditioning, which consisted of thiotepa, fludarabine, and cyclophosphamide (TFC) for patients with an HLA identical sibling donor, TFC plus anti-thymocyte globulin for matched unrelated (MUD) donors, TFC plus alemtuzumab and 2-Gray (Gy) total body irradiation (TBI) for T-deplete haploidentical alloSCT, or TFC plus 2-Gy TBI and post-transplant cyclophosphamide for T-replete haploidentical alloSCT. Multivariate analysis of alloSCT outcomes included as covariates the pre-transplant disease status (CR vs PR vs resistant), donor (HLA identical, MUD, or T-deplete or T-replete haploidentical), primary refractory disease (yes vs no) and timing of relapse after ASCT (<12 mos after ASCT vs >12 mos vs no ASCT). Patients had a median of 33 years at alloSCT, 76% of them had a primary refractory disease at diagnosis. 74% of patients relapsed <12 months after ASCT, 15% relapsed >12 months after ASCT, 11% underwent alloSCT without previous ASCT. At alloSCT, 25% had resistant disease whereas 75% were in partial (31%) or complete response (44%) after the last salvage treatment. Donors were HLA identical siblings (42%), MUD (29%), or haploidentical (21% T-deplete, 8% T-replete). Median follow-up was 5.4 years. Three- and 5-years OS was 61 and 59%, PFS and relapse incidence were 46% and 38% at both 3 and 5 years. Non-relapse mortality (NRM) was 10% at 100 days, 17% at 1 year and for the entire follow-up. In multivariate analysis, the timing of relapse after ASCT and primary refractory disease did not impact the transplant outcomes. OS was reduced by resistant disease at alloSCT (HR=4.01, CI95% 1.34-11.97, p=0.012) and by T-depleted haploidentical transplant (HR=3.81, CI 95% 1.36-10.66, p=0.010). PFS and relapse incidence were impacted only by resistant disease (HR=5.54, CI 95% 2.13-14.37, p<0.001, and HR=6.75, CI 95% 2.07-21.96, p=0.001, respectively). NRM was significantly impacted only by the use of T-depleted haploidentical grafts (HR=7.63, CI95% 1.07-54.31, p=0.042). In conclusion, the pre-transplant disease status and not the timing of relapse after ASCT or primary refractory disease, impacts OS, PFS and relapse of RR-HL patients allografted with thiotepa-based conditioning. An optimal response before alloSCT is critical to maximize the long-term benefit of alloSCT. In the era of novel agents this can be a realistic goal for the majority of patients. Disclosures Viviani: Takeda Italia SpA: Consultancy; Teva Italia SpA: Consultancy; Italfarmaco SpA: Consultancy; Takeda International: Consultancy.

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An Alternative Donor Is a Valid Option Compared to a Matched-Unrelated in Allogeneic Stem Cell Transplantation for Acute Lymphoblastic Leukemia in CR2: A Report of 841 Patients from the EBMT Acute Leukemia Working Party

Blood ◽

10.1182/blood.v128.22.3497.3497 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3497-3497

Author(s):

Eolia Brissot ◽

Myriam Labopin ◽

Domenico Russo ◽

Sonja Martin ◽

Christoph Schmid ◽

...

Keyword(s):

Multivariate Analysis ◽

Stem Cell ◽

Acute Lymphoblastic Leukemia ◽

Stem Cell Transplantation ◽

Predictive Factors ◽

Lymphoblastic Leukemia ◽

Univariate Analysis ◽

Unrelated Donor ◽

Free Survival ◽

Matched Sibling

Abstract Background: In acute lymphoblastic leukemia (ALL) in CR1, the indications of allogeneic stem cell transplantation (allo-SCT) remain under debate, given the recent availability of new therapeutic tools including novel chemotherapy agents, monoclonal antibodies and T cell cellular therapies as well as sensitive molecular techniques to assess minimal residual disease (MRD). In contrast, allo-SCT for ALL in CR2 is a well-established procedure. At the same time, unmanipulated grafts are increasingly used in the haplo-setting, and innovative regimens for GvHD prophylaxis have been adopted with encouraging results. Aims : The current study aimed to compare the outcomes of ALL patients (pts) who do not have a matched sibling and received allo-SCT in CR2 from a matched-unrelated donor 10/10 (MUD) versus alternative donors: unrelated donor 9/10 (UD), cord blood unit (CBU) and haplo-identical T replete donor (HD). Methods: Patients with ALL in CR2 who underwent a first allo-SCT with a MUD or an UD, a CBU or HD, reported between 2005 and 2015 to the registry of the EBMT ALWP, were included. The major endpoints were to assess overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), non-relapse mortality (NRM), and graft-versus-host disease-free, relapse-free survival (GRFS) Results: Four hundred twenty eight pts received a MUD 10/10, 171 pts an UD 9/10, 148 pts a CBU and 94 a T replete HD. Median age was lower in the CBU group compared to the other groups (26.1 yrs (18-76) vs 31.6 (18-74) , p<10-4). There was a higher proportion of patients who underwent allo-SCT within 18 months following diagnosis in the HD group :42.5% vs 32.5%, p=0.05 (36.9% in MUD 10/10, 28% in UD 9/10, and 24% in CBU groups, respectively). The median time to relapse to transplant was similar in the 4 groups (p=0.68). The number of Philadelphia chromosome positive ALL pts and of positive MRD at transplant were comparable in the 4 groups (p=0.60 and p=0.74, respectively). At 2 years, for the overall population, LFS was 36.9% (95% CI: 33.2-40.6), OS 42.6% (95% CI: 38.8-46.5), RI 32.4% (95% CI: 28.9-35.9), NRM 30.7% (95%CI: 27.4 -34.1), and GRFS 30% (95%CI: 26-33). As to the outcomes, in univariate analysis, no differences were found between the 4 groups. In multivariate analysis, 3 predictive factors were associated with an improved LFS: the time from diagnosis to transplant >18months (DxTx>18 m)(HR=0.66, 95%CI, 0.54-0.81, p<10-4), a Karnofsky score at transplant ≥90% (KS) (HR=0.77, 95%CI, 0.62-0.97, p=0.02),and the year of transplant (HR=0.95, 95%CI: 0.91-0.99, p=0.02), whereas age was associated with a lower LFS (HR=1.103 per 10 years, 95%CI:1.023-1.19, p=0.01).For OS, HD compared to MUD 10/10, patient age, and CMV positivity were associated with lower OS (HR=1.42, 95%CI 1.02-1.99, p=0.04; HR=1.10, 95%CI 1.02-1.19, p=0.018; and HR=1.27, 95%CI 1.02-1.58, p=0.03; respectively), whereas 3 predictive factors were associated with better OS: DxTx>18m, KS ≥90% and the year of transplant. In multivariate analysis for RI, only DxTx>18m was a protective factor (HR=0.49, 95%CI, 0.38-0.65, p<10-4). In multivariate analysis for GVHD II-IV, a HD was associated with a higher risk compared to MUD 10/10 (HR=0.028, 95%CI: 1.05-2.30, p=0.03). At 2 years, in univariate analysis, the cumulative incidence of chronic GVHD was not statistically different between the 4 groups and no risk factors were identified in multivariate analysis. In multivariate analysis for NRM, patient age and CMV positivity were factors associated with a higher NRM (HR=1.14, 95%CI, 1.03-1.27, p=0.015; HR=1.50, 95%CI, 1.09-2.05, p=0.011), while year of transplant was the only factor associated with lower NRM (HR=0.94, 95%CI, 0.88-0.99, p=0.027). Finally, considering GRFS at 2 years, DxTx>18m and the year of transplant were associated with better GRFS (HR=0.69, 95%CI, 0.57-0.84, p<10-3 and HR=0.96, 95%CI, 0.92-0.99, p=0.04). Conclusion Allo-SCT may rescue more than one third of pts with ALL in CR2. Importantly, once a matched sibling donor is not available the donor type being unrelated or alternative did not have any impact on patients' LFS, RI, NRM and GRFS. When compared to a MUD 10/10, an T replete HD was associated with lower OS and higher aGVHD II-IV. Interestingly, DxTx>18m was a major prognostic factor for both LFS and RI. Therefore, as compared to a MUD 10/10, a UD 9/10, a CBU, but also a T replete HD could be considered as valid options in adult pts with ALL in CR2. Disclosures Apperley: Bristol Myers Squibb: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Incyte: Speakers Bureau; Ariad: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau.

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Risk Factor of Hepatic Veno-Occlusive Disease: Analysis of Clinical Data of 5024 Patients Extracted from the Database of the Japan Marrow Donor Program.

Blood ◽

10.1182/blood.v108.11.2970.2970 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2970-2970

Author(s):

Miwa Sakai ◽

Kazuteru Ohashi ◽

Takuya Yamashita ◽

Hideki Akiyama ◽

Hisashi Sakamaki

Keyword(s):

Risk Factors ◽

Multivariate Analysis ◽

Stem Cell ◽

Clinical Data ◽

Univariate Analysis ◽

Disease Status ◽

Occlusive Disease ◽

Blood Type ◽

Hematopoietic Stem ◽

Increased Risk

Abstract Hepatic veno-occlusive disease (VOD) is one of the most serious complication of hematopoietic stem cell transplantation (HSCT). Various factors have been identified as increasing the risk of hepatic VOD, but few of them have been associated with a significantly increased risk. We retrospectively analyzed the clinical data of 5024 transplant recipients (median age28, range 0–68) which extracted from the Japan Marrow Donar Program. The diagnosis of VOD was made according to the McDonald’s criteria, and 324 out of 4833 patients (6.7%) were eventually diagnosed with VOD. The possible risk factors based on the previous studies were counted on an initial univariate analysis, and cumulated significant factors were further analyzed for their potential value for VOD development in multivariate analysis. Variables correlated with an increased risk of VOD were: time of transplant >2 times (relative risk (RR) 2.7; p=0.006), pretransplant disease status (RR 2.3; p=0.000), prior liver disease (RR 2.1; p=0.017), ABO blood type mismatch (RR1.7; p=0.000). In patients receiving either busulfan or melphalan for conditioning increased VOD risk (RR 1.5 and 1.8; p=0.007 and 0.002, respectively). In our multivariate analysis, stem cell source, and prophylactic use of heparin and Ursodiol had no significant effect on VOD development. This analysis might contribute to revise the previously reported risk factors for VOD and the data could be used to know which patients might be suitable subjects for new trials for VOD prevention.

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Impact of Infused Peripheral Blood Stem Cell Parameters (Total Nucleated Cells, CD34+ Cells, CD3+ Cells and CFU-GM) on Transplant Outcome after Reduced Intensity Allogeneic HSCT.

Blood ◽

10.1182/blood.v110.11.3048.3048 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3048-3048

Author(s):

Mauricette Michallet ◽

Quoc-Hung Le ◽

Anne Thiebaut ◽

Sophie Ducastelle ◽

Nicole Raus ◽

...

Keyword(s):

Multivariate Analysis ◽

Stem Cell ◽

Disease Status ◽

Low Risk ◽

Transplant Outcome ◽

Cd34 Cells ◽

Recipient Age ◽

The Impact ◽

Cmv Status ◽

Reduced Intensity

Abstract This study concerns the impact of infused PBSC parameters [total nucleated cells (TNC), CD34+ cells, CFU-GM and CD3+ cells] associated with the other pre-transplant variables on the transplant outcome after allogeneic reduced intensity conditioning hematopoietic stem cell transplantation (HSCT). There were 95 patients, 58 males and 37 females with a median age of 53 years (27–66.5). The diagnosis pre-transplant were 21 AML, 1 ALL, 8 CML or MPS, 10 CLL, 16 MDS, 9 NHL, 3 HD, 27 MM. The disease status pre-transplant were 29 CR, 38 PR, 10 stable disease (SD) and 18 progressive disease (PD) and we defined a low risk subgroup of 38 patients (40%) including all diseases in CR1 and MM in CR, PR1 or PR2. For conditioning, 31 patients received an association of Fludarabine and TBI, 54 Fludarabine, Busulfan and ATG (FBA) (ATG 2.5mg/kg:15, ATG 5mg/kg: 27, ATG 7.5–12.5mg/kg:12) and 10 received other associations. All patients received PBSC from 93 HLA identical sibling donors and 2 from 1 antigen HLA mismatched related donors with donor median age of 52 years (29–73). Fifty-eight patients were sex mismatched (F/M:36, M/F:22), for CMV status: 26 pairs were negative, 38 positive and 31 mismatched and 28 patients presented an incompatibility ABO Rhesus with their donors. The patients received a median number of TNC 9.41× 108/Kg (2.6–25), CD34+ cells 6×106/Kg (1.2–64), CD3+ cells 262 ×106/Kg (32.8–761) and CFU-GM of 127×104/Kg (12–470). After transplant, 41 patients developed an acute GVHD ≥ grade II (II: 16, III: 10 and IV: 15) and 39 patients a chronic GVHD (15 limited, 24 extensive). With a median follow-up of 24.5 months, 43 patients have relapsed and 37 are alive. The probability of OS and EFS at 3 years was 35.4% [26–48] and 23% [15–35] respectively and the TRM at 1 year 24%. The results of the multivariate analysis using a Cox proportional hazard model and a logistic regression stepwise procedure are shown in the table 1. In conclusion, this study shows a significant impact of recipient age, low risk disease, sex mismatching, FBA 2.5mg/kg, CMV status and TNC and demonstrates among the infused PBSC parameters the very important role of the CFU-GM number on transplant outcome after RICT. Table 1: Multivariate analysis OS EFS TRM AGVHD cGVHD Disease status pre-transplant, type of donor, type of conditioning, HLA matching, ABO matching: NS Recipient Age HR:1.09 (1.01–1.16) HR:1.19 (1.03–1.38) HR:0.91 (0.84–0.99) HR:0.91 (0.84–0.99) p=0.01 p=0.02 p=0.04 p=0.04 Sex Matching HR:0.16 (0.03–0.89) p=0.04 CMV Status HR:0.11 (0.01–0.9) HR:0.11 (0.01–0.9) p=0.04 p=0.04 Low risk Disease HR:0.13 (0.02–0.77) HR:0.02 (0.001–0.04) HR:0.02 (0.001–0.04) p=0.02 p=0.01 p=0.01 FBA 2.5mg/kg HR:6.46 (1.50–27.71) p=0.01 TNC HR:1.19 (1.06–1.35) p=0.03 CFU-GM HR:1 (0.98–1.14) HR:1.006 (1.002–1.01) HR:1.01 (1.001–1.02) HR:0.99 (0.98–1) p=0.03 p=0.004 p=0.02 p=0.05

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Determinants of Higher Pre-Apheresis CD34+ Count in Patients Undergoing Autologous Hematopoietic Stem Cell Mobilization

Blood ◽

10.1182/blood.v118.21.4387.4387 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4387-4387

Author(s):

Alexandre Chiattone ◽

Rima M Saliba ◽

Viviane C. Chiattone ◽

XiaoWen Tang ◽

Nelson Hamerschlak ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Univariate Analysis ◽

Disease Status ◽

Stem Cell Mobilization ◽

Cancer Center ◽

Hematopoietic Stem ◽

Study Population ◽

Cell Mobilization ◽

Wbc Count

Abstract Abstract 4387 Absolute peripheral blood (PB) pre-apheresis CD34+ count has been shown to predict the CD34+ yield/Kg in patients undergoing autologous stem cell mobilization and apheresis. Determining correlates of PB pre-apheresis CD34+ counts would facilitate identifying patients that may be at high risk of mobilization failure. Methods. A total of 851 consecutive autologous apheresis procedures were performed at M.D. Anderson Cancer Center between January 2005 and December 2009. We randomly selected half (N=413) of this study population to serve as a study sample (described in table), and preserved the remaining for validation studies. In this study population, we observed that 96% of patients with PB pre-apheresis CD34+ counts of >40/μL collected >2×106 CD34+cells/Kg on the first day of apheresis. We sought to determine patient and disease characteristics that are associated with higher PB pre-apheresis CD34+ counts (>40/μL). These factors included patient age (quartiles), gender, weight (quartiles), diagnosis (Multiple Myeloma vs. Hodgkin's and Non-Hodgkin's Lymphoma), disease status at transplant (remission vs. active disease), number of prior chemotherapy regimens (< 2 vs. ≥2), blood count on day of collection: hemoglobin level (≤10 vs. >10 g/dL), WBC (<4 vs. ≥ 4 ×109/L), absolute neutrophil count [ANC] (< vs.≥ median), and platelet count (≤150 vs. <150 ×109/L); and number days (≤ vs. > median) from the beginning of mobilization to the first apheresis procedure. Results. On univariate analysis, shorter duration from beginning of mobilization therapy to first day of apheresis (odds ratio [OR] =4.7, p <0.001), and weight >95 Kg (OR=1.8, p=0.01), were significantly associated with a PB CD34+count >40/μL; whereas a diagnosis of Multiple Myeloma (OR=0.5, p=0.002), age >60 years (OR=0.6, p=0.009), pre-apheresis WBC <4 × 109/L (OR=0.5, p=0.004) and ANC (< median p=0.003) were significantly associated with PB CD34+ counts of ≤ 40/μL. These factors, with the exception of age, remained significant on multivariate analysis. Shorter duration of mobilization (OR=8.1, p<0.001) had the strongest association with PB CD34+ count >40/μL. A diagnosis of Multiple Myeloma was associated with lower PB CD34+ count in patients who had a shorter mobilization course (OR=0.3, p<0.001), but not in those who took longer to mobilize. Lower WBC and ANC counts were associated with lower PB CD34+ count, and this effect was more pronounced for patients who had both low WBC and ANC (OR=0.4, p=0.001) than for those who had low ANC but high WBC count (OR=0.5, p=0.025). Weight >95 Kg was still associated with higher PB CD34+ count, (OR=1.9, p 0.01). There was no association between PB CD34+ count and any of the remaining factors evaluated. Conclusion: Our data suggest that patients who take longer to mobilize, have low WBC and [ANC] pre-apheresis might benefit from early intervention with novel mobilization strategies. Totals may vary because of missing data. Disclosures: Popat: Otsuka: Research Funding.

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Comparison of Matched-Sibling Donors Versus Unrelated Donors in Allogeneic Stem Cell Transplantation (allo-SCT) for Primary Refractory Acute Myeloid Leukemia (PRF AML): A Report of 1041 Patients from the Acute Leukemia Working Party of the EBMT

Blood ◽

10.1182/blood.v126.23.196.196 ◽

2015 ◽

Vol 126 (23) ◽

pp. 196-196

Author(s):

Eolia Brissot ◽

Myriam Labopin ◽

Matthias Stelljes ◽

Gerhard Ehninger ◽

Gernot Stuhler ◽

...

Keyword(s):

Multivariate Analysis ◽

Stem Cell ◽

Predictive Factors ◽

Research Funding ◽

Univariate Analysis ◽

Conditioning Regimen ◽

Factors Associated ◽

Donor Type ◽

Unrelated Donors ◽

Matched Sibling

Abstract Background: PRF-AML is associated with a dismal prognosis. Approximately one third of patients younger than 60 years, and 50 % of older patients, with newly diagnosed AML, fail to achieve complete remission (CR) with standard induction chemotherapy. Allo-SCT in the setting of active disease is an alternative strategy. The increased availability of unrelated donors (UD) together with the use of reduced-intensity conditioning (RIC) regimens have opened the possibility for transplantation to a larger number of patients in comparison to standard myeloablative regimens (MAC). Because of the high risk of allo-SCT in this setting, there are still questions on the patient outcome depending on the donor type. Aims: The current study aimed to compare the outcomes of allo-SCT from matched sibling donors (MSD) (n=660) vs UDs (n=381), for patients with PRF AML. Methods: The major endpoints were to assess overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and non relapse mortality (NRM). Results: 660 patients received a MSD, 296 patients a matched UD (10/10) and 85 a mismatched UD (9/10), respectively. Median age was higher in the UD group (50.5 yrs (18-74) vs 47.7 yrs (18-74), p=0.006). The median time from diagnosis to allo-SCT was similar (110 days [60-180] in the MSD group vs 111days [60-178] in the UD group; p=0.33). In the MSD allo-SCT, 57 % received a MAC regimen, 29% a RIC regimen, and 14% a sequential conditioning regimen; while, in the UD transplants, 44.4 % received a MAC regimen, 24.4% a RIC regimen, and 31.2% a sequential conditioning regimen (p<10-4). Peripheral blood stem cell (PBSC) was the main stem cell source (92% in the MSD allo-SCT vs 94.8% in the UD allo-SCT, p=0.09). Median follow-up was statistically longer in the UD group than in the MSD group (19 months [range, 1.5-143] vs 16 months [2-153], respectively, p=0.04). In univariate analysis, LFS at 2 years was 25.3% in MSD group vs 28.3% in UD group (p=0.56) (Fig.1). In multivariate analysis, 2 predictive factors were associated with lower LFS: cytogenetics (poor vs intermediary; HR=1.61, 95%CI,1.24-2.09, p=0.0004) and time from diagnosis to transplant (above the median 110 days) (HR=1.21, 95%CI,1.02-1.44, p=0.03), whereas Karnofsky status at transplant ≥90% (KS) was associated with better LFS (HR=0.67, 95%CI,0.56-0.80, p=0.0001). In univariate analysis, OS at 2 years was comparable in both groups (30.9% in MSD group vs 34.3% in UD group (p=0.57)) (Fig2). In multivariate analysis, 4 predictive factors were associated with lower OS: age>50 yrs, cytogenetics, time from diagnosis to transplant and CMV positive status whereas Karnofsky status at transplant ≥90% (KS) was associated with better OS. 71% patients with a MSD and 68.6% patents with an UD reached CR after allo-SCT (p=0.73). In univariate analysis, RI at 2 years was 53.7% in MSD group and 56.4% in UD group, respectively (p=0.038). In multivariate analysis for RI, cytogenetics and time from diagnosis to transplant were the only risk factors associated with increased relapse [(HR=1.74, 95%CI,1.30-2.33, p=0.0002) (HR=1.29, 95%CI,1.06-1.58, p=0.01), respectively] whereas KS was a protective factor (HR=0.77, 95%CI,0.62-0.95, p=0.01). The incidence of aGVHD≥2 was higher in UD group (35.5% vs 27.9%, p=0.012). At 2 years, the cumulative incidence of chronic GVHD (cGVHD) was not statistically different between MSD and UD (28.9% and 25.8%, respectively, p=0.56) (univariate analysis). As for, NRM at 2 years, there was not statistical difference between MSD and UD groups (21% vs 25.1%, p=0.112). In multivariate analysis, patient age (>50 yrs) and CMV positive status were factors associated with higher NRM (HR=1.77, 95%CI, 1.27-2.47, p=0.001; HR=1.68, 95%CI, 1.14-2.47, p=0.008), while RIC regimen compared to MAC regimen was the only factor associated with lower NRM (HR=0.59, 95%CI, 0.41-0.85, p=0.005). Conclusion Allo-SCT may rescue one third of patients with primary refractory AML. Importantly, the donor type did not have any impact on PRF patients' outcomes. In contrast, time to transplant was a major prognostic factor for LFS and OS. For patients with PRF AML, that do not have a matched sibling donor, allo-HST from UD is a suitable option and thus initiation of an early search and allocating of a suitable donor is therefore indicated. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Finke: Riemser: Research Funding, Speakers Bureau; Neovii, Novartis: Consultancy, Research Funding, Speakers Bureau; Medac: Research Funding. Esteve:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Mohty:Janssen: Honoraria; Celgene: Honoraria.

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