Higher Incidence and Risk of Developing Second Solid Cancers (SSC) after Haematopoetic Stem Cell Transplantation (HSCT) As Compared to General Population

Abstract Introduction: As the number of long-term survivors following HSCT is increasing, the long-term risks and associated morbidity has become important component of survivorship program. The known risk factors for developing cancer include use of chemotherapy agents, radiation exposure, immune dysfunction, previous malignancy in addition to other factors and as HSCT process involves all these factors, this single centre retrospective analysis was undertaken to evaluate the risk of developing SSC in the patients receiving transplant. Methods: From February 1982 to February 2016, 2231 patients received 2495 transplants (median age: 46yr., range: 14-76 yr.; M: 1586, F: 909) for haematological malignancies (Leuk: 744, lymphoma:767, myeloma:848, solid tumours/other:136). Donor was allogeneic (n=744) or autologous (n=1751) and conditioning was with (n=614) or without TBI (n=1881). Donor was sibling (n=375), matched unrelated (n=355), haploidentical relative (n=3) or umbilical cord blood (n=11). Source of stem cell was marrow (n=367), PBSC (n=2086), both (n=31) or cord blood (n=11). GVH prophylaxis included Campath or ATG in 369 cases. Of all the patients 1985 received single transplant, 231 had two, 13 had 3 and 2 had 4 HSCT procedures. Data was analysed as of 15/04/2016 using competing risk model with death as the competing event. Comparison of incidence to general population was performed by computing standardized incidence rates (SIR). Patients with second haematological malignancy were not included in this analysis. Results: Median follow-up was 5.3 years (range: 0-32 years). Patient follow-up was more than 10 years in 467 cases (19%), between 5 to 10 years in 430 (17%), 2 to 5 years in 607 (24%) and less than 1 year in 997 cases (40%). 36% patients were followed-up for more than 5 years. Second solid cancers developed in 116 patients with the incidence of 1% at 5yr (95% CI: 0.5-2.6), 3% at 10 yr (95% CI: 1.6-5.3), 6% at 15yr (95%CI: 3.6-8.8) and 10% (95% CI: 5.9-15.5) at 20 years. Median time to develop SSC from date of HSCT was 11 yr (range: 0.4-28.1 yr). Primary site for SSC included skin (n=37), breast (n=22), GI (n=15), GU (n=16), H&N (n=10), lung (n=6), CNS (n=4), Endocrine (n=4) & HPB (n=2). There was no difference with type of transplant i.e. auto or allograft. Autograft and allograft groups were analysed separately. In univariate analysis, allograft group showed higher cumulative incidence of SSC with use of PBSC (p<0.0001), campath/ATG (p=0.0002), donor other than sibling (P=0.0004), RIC (p<0.0001), non-TBI conditioning (p=0.007), older age at transplant (0.008), development of agvhd or cgvhd (p=0.023) and transplant year after 2000 (p=0.01). In multivariate analysis age above 50 (RR: 1.8, 95%CI: 1.2-1.8, p=0.046) and RIC (RR: 4.4, 95% CI: 1.2-8.3, p=0.03) were independently associated with higher risk of SSC. In autograft group, there were no independent risk factors in univariate or multivariate analysis. As compared to general population incidence was higher for all cancers (SIR=7.4) and also cancers at every primary site. Risk was highest for breast (SIR=14.3), Head/neck (SIR=25.6), brain (SIR=17.4) and colon (SIR=6.2). Overall survival is significantly shorter in patients who develop SSC (median: 12 yr vs. not reached, p<0.0001). The median time to develop SSC from the date of HSCT has significantly shortened over last three decades (years 1982-1990: 21yr, 1991-2000: 11.1 yr, 2001-2010: 6.34 yr, 2011-2016: 2.2 yr; p=0.0001) Conclusion: This single centre analysis confirms that the risk of developing SSC increases with advancing age, use of RIC allograft, longer follow-up and leads to inferior survival. Since the year 2000, SSC are developing early after transplant and it needs to be evaluated if this is a trend seen at other centers and if so, is it related to increasing use of RIC, increasing number of elderly patients, severity of immune-suppression or higher incidence of GVHD. Disclosures Somervaille: Novartis: Consultancy, Honoraria; Imago Biosciences: Consultancy. Bloor:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; GSK: Consultancy, Speakers Bureau; Gilead: Honoraria; Abbvie: Membership on an entity's Board of Directors or advisory committees.

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Prognostic Factors for Developing Thrombosis in Polycytemia Vera: A Retrospective Analysis of 331 Patients with Long-Term Follow-up Highlights the Importance of White Blood Cells Levels

Blood ◽

10.1182/blood-2020-139431 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 48-49

Author(s):

Samantha Ferrari ◽

Chiara Pagani ◽

Mariella D'Adda ◽

Nicola Bianchetti ◽

Annamaria Pelizzari ◽

...

Keyword(s):

Risk Factors ◽

Multivariate Analysis ◽

High Risk ◽

Board Of Directors ◽

Advisory Board ◽

Advisory Committees ◽

Risk Status ◽

History Of ◽

Wbc Count

Polycythemia Vera (PV) is a chronic myeloproliferative neoplasm characterized by erythrocytosis, constitutively active mutations in JAK2 and an increased susceptibility to thrombotic events (TEs). There is still controversy about the role of increased hematocrit and of other variables including elevated white blood cell count as risk factors for the occurrence of TEs. A better definition of the relative prognostic importance of hematologic parameters would help us to better tailor the therapeutic approach to PV patients (pts), which is currently mainly based on the use of acetilsalycilic acid (ASA), venesection and hydroxyurea . The aim of our study was to analyze if any clinical or laboratory variables were significantly associated to the occurrence of TEs both at PV diagnosis and during the course of the disease in a large series of PV pts uniformly followed at a single Center over a period of 29.5 years from January 1986 to June 2019. Clinical and laboratory data were obtained from the time of diagnosis until death, progression to acute leukemia or last follow-up. Hematocrit (Hct), hemoglobin (Hb), white blood cell (WBC) and platelet (PLT) levels were recorded for each patient at least every 6 months. Among a total of 331 pts, the median age was 65 years (range 30-92 years), and 56% were male. "High risk" features (age ≥ 60 years and/or history of prior thrombosis) were present in 221 pts (66.7%). The incidence of cardiovascular risk factors was: hypertension 64%, diabetes 15%, hyperlipidemia 28%, history of active or remote smoking 41%. Patients on ASA were 279 (84%), 19 (6%) were on oral anticoagulation, while 27 (8%) were on ASA+oral anticoagulant. At PV diagnosis 54 pts (16%) presented with thrombosis, arterial in 32 (59%) and venous in 22 (41%). A previous TE was recorded in 57 pts (17%): in 43 (75%) arterial, in 12 (22%) venous and in 2 (3%) mixed (arterial+venous). Previous thrombosis was the only variable significantly associated with the presence of a TE at PV diagnosis (P=0.02). After PV diagnosis, with a median follow-up of 81 months (range 1-374 months), 63 pts (19%) experienced a TE and 11 of them a further episode, for a total of 74 TEs. The incidence rate (pts/year) of TEs was 2.7%. Forty-two events were arterial (57%), 31 were venous (42%) and 1 (1%) was mixed. It was the first TE for 37 pts. Cerebrovascular accidents and deep-venous thrombosis were the most frequent arterial and venous TEs both at PV diagnosis and throughout the disease course, with a relative incidence of 50% and 32% respectively. The table compares the characteristics of patients who did or did not develop a TE after PV diagnosis. At univariate analysis, PV high risk status, a previous TE and hyperlipidemia at PV diagnosis were significantly associated with a subsequent TE. Among hematologic variables an elevated WBC count at the time of thrombosis, but not Hct or PLT levels, was highly significantly associated with the development of a TE. At multivariate analysis, WBC count ≥10.4 x 10^9/L and hyperlipidemia maintained their independent prognostic value, while high risk status and a previous TE lost their prognostic significance. Both at univariate and multivariate analysis, hyperlipidemia at diagnosis (P=0.009 and P=0.002) and high WBC count at thrombosis (P=0.001 and P=<0.0001) predicted for arterial thromboses, while only a history of prior thrombosis (P=0.03) predicted for venous ones. In conclusion, our analysis confirms that elevated WBC count at the moment of the event more than increased hematocrit is associated to the development of thrombosis in PV pts. We also found that hyperlipidemia was an independent risk factor for arterial thrombosis, calling for an accurate management of increased lipid levels. Whether a reduction of the WBC count during the course of PV may reduce the frequency of TE remains to be demonstrated by prospective studies. Table Disclosures D'Adda: Novartis: Other: Advisory board; Incyte: Other: Advisory board; Pfizer: Other: Advisory board. Rossi:Daiichi Sankyo: Consultancy, Honoraria; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Advisory board; Alexion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.

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Stem Cell Transplantation Can Provide Durable Disease Control in Blastic Plasmacytoid Dendritic Cell Neoplasia (BPDC): A Retrospective Study From the European Group for Blood and Marrow Transplantation (EBMT)

Blood ◽

10.1182/blood.v118.21.3077.3077 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3077-3077

Author(s):

Sascha Dietrich ◽

Damien Roos-Weil ◽

Ariane Boumendil ◽

Emanuelle Polge ◽

Jian-Jian Luan ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Board Of Directors ◽

Cell Transplantation ◽

Research Funding ◽

Nk Cell ◽

Plasmacytoid Dendritic Cell ◽

Advisory Committees

Abstract Abstract 3077 Blastic plasmacytoid dendritic cell neoplasm (BPDC), formerly known as blastic NK cell lymphoma, is a rare hematopoietic malignancy preferentially involving the skin, bone marrow and lymph nodes. The overall prognosis of BPDC is dismal. Most patients show an initial response to acute leukemia-like chemotherapy, but relapses with subsequent drug resistance occur in virtually all patients resulting in a median overall survival of only 9–13 months. However, anecdotal long-term remissions have been reported in young patients who received early myeloablative allogeneic stem cell transplantation (alloSCT). We therefore performed a retrospective analysis of patients identified in the EBMT registry in order to evaluate the outcome of autologous stem cell transplantation (autoSCT) or alloSCT for BPDC. Eligible were all patients who had been registered with a diagnosis of BPDC or Blastic NK cell lymphoma and had received autologous stem cell transplantation (autoSCT) or alloSCT in 2000–2009. Centres were contacted to provide a written histopathology and immunophenotyping report and information about treatment and follow-up details. Patients who did not have a diagnostic score ≥ 2 as proposed by Garnache-Ottou et al. (BJH 2009) were excluded. RESULTS: Overall, 139 patients could be identified in the database who fulfilled the inclusion criteria (alloSCT 100, autoSCT 39). Of 74 patients for whom the requested additional information could be obtained, central review confirmed the diagnosis of BPDC in 39 patients (34 alloSCT, 5 autoSCT). The 34 patients who had undergone alloSCT had a median age of 41 years (range: 10–70 years), were transplanted from a related (n=11) or unrelated donor (n=23); received peripheral blood stem cells (n=9), bone marrow stem cells (n=19) or cord blood (n=6); and had been treated with a reduced intensity conditioning regimen (RIC, n=9) or myeloablative conditioning (MAC, n=25). Nineteen of 34 patients were transplanted in CR1. After a median follow up time of 28 months (range: 4–77+ months), 11 patients relapsed (median time to relapse: 8 months, range: 2–27 months) of whom 8 died due to disease progression. 9 patients died in the absence of relapse. No relapse occurred later than 27 months after transplant. Median disease free survival (DFS) was 15 months (range: 4–77+ months) and median overall survival (OS) was 22 months (range: 8–77+ months; Figure 1a). However, long-term remissions of up to 77 months after alloSCT could be observed. Patients allografted in CR1 tended to have a superior DFS (p=0.119) and OS (p=0.057; Figure 1b). MAC was associated with a better OS (p=0.001) which was attributable to the significantly higher non-relapse mortality (NRM) rate of patients after RIC (p=0.014), who had been significantly older (age RIC: 56 years, age MAC: 36 years, p=0.0014). The relapse rate was not different in patients after RIC and MAC, respectively. However, there was no survivor after RIC. Median age in the autoSCT group was 47 years (range: 14–62 years). Three of 5 patients were transplanted in CR1 of whom 1 patient relapsed after 8 months, 1 patient experienced treatment related mortality and 1 patient remained in CR for 28 months. The 2 remaining patients had more advanced disease at autoSCT and relapsed 4 and 8 months thereafter. CONCLUSION: AlloSCT is effective in BPDC and might provide curative potential in this otherwise incurable disease, especially when performed in CR1. However, it remains to be shown by prospective studies if the potential benefit of alloSCT in BPDC is largely due to conditioning intensity, or if there is a relevant contribution of graft-versus-leukemia activity. Disclosures: Tilly: Seattle Genetics, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau, Travel/accommodations/meeting expenses; Genentech: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Research Funding, Speakers Bureau; Pfizer: Speakers Bureau; Janssen Cilag: Speakers Bureau.

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Allogeneic Stem Cell Transplantation Is Associated with Prolonged Disease Control in Chemosensitive Aggressive Histology Lymphoma Patients When Done Early

Blood ◽

10.1182/blood.v118.21.4525.4525 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4525-4525

Author(s):

Auro Viswabandya ◽

Tony Panzarella ◽

Dennis Dong Hwan Kim ◽

Vikas Gupta ◽

Jeffrey H. Lipton ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Board Of Directors ◽

Allogeneic Stem Cell Transplantation ◽

Chronic Gvhd ◽

Advisory Committees ◽

Aggressive Histology ◽

Grade 3

Abstract Abstract 4525 Introduction Allogeneic stem cell transplantation (Allo-SCT) is a treatment option in aggressive histology lymphoma (AG-NHL) patients who have either failed or relapsed after autologous SCT (ASCT) or if the potential for long term disease control after ASCT is limited. There is limited data in literature regarding the long term outcome of allo-SCT in AG-NHL. Methods We did a retrospective analysis of all aggressive histology patients who underwent Allo-SCT between 1989 and 2009 at our centre. A total of 41 patients with AG-NHL [diffuse large B cell lymphoma (DLBCL) and variants, follicular lymphoma grade 3 (FL3), biopsy proven aggressive transformation of indolent lymphoma (TRIL)] underwent Allo-SCT. All patients were in a chemosensitive remission at time of transplantation. The conditioning regimen was BU-CY in the majority (36 or 88%) of patients and 3 patients had reduced intensity transplantation (RIC) with fludarabine-based regimens. GVHD prophylaxis was cyclosporine and methotrexate until 2009 and was cyclosporine and mycophenolate mofetil after that. Alemtuzumab was used in matched unrelated donor (MUD) transplants in 5 (12%) cases. Results There were 22 (54%) males and 19 (46%) females. The median age at BMT was 48 years (range: 20–65). Fifteen (37%) had DLBCL, 19 (46%) had TRIL and 7 (17%) had FL3. Fifteen (37%) patients had received 2 or less lines of chemotherapy and 26 (63%) had received more than 2 lines of therapy at time of transplantation. The median number of chemo regimens was 3 (range: 1–7). The chemotherapy regimens included prior anthracyclines in 40 (98%), prior platinum in 26 (63%) and prior mini BEAM in 19 (46%). Six (15%) patients had received Rituximab and 9 (22%) had received prior RT. Seven (17%) patients had prior ASCT. Thirty-five (85%) of patients received matched related donor transplant whereas 5 (12%) received MUD transplant. The graft source was bone marrow in 33 (80%) and peripheral blood stem cells in 8 (20%). Grade 1–2 acute GVHD was seen in 53% and grade 3–4 in 9%. Chronic GVHD was seen in 51% patients. With a median follow up of 49 months and 96 months in those who are alive, five (12%) patients have relapsed, 20 (49%) patients are alive and in remission. Non relapse mortality (NRM) was 16/41 (39%) and predominantly related to infection. The overall survival (OS) and progression free survival (PFS) of the entire cohort at 60 months was 55% (Fig-1). Patients, who had achieved CR pre-allo-SCT (compared to PR) had a statistically significantly improved PFS and OS (100% survival for those who were in CR). In multivariate analysis, number of chemotherapy regimens (≤2) was associated with improved OS (p=0.015) and presence of chronic GVHD showed a trend towards significant OS (p=0.052) Conclusions With a median follow up of 96 months in survivors, myeloablative allo-SCT is associated with durable remission in patients with chemosensitive AG-NHL. Results are less favourable in patients who have received multiple prior regimens. NRM remains a significant concern with myeloablative regimens. We believe there is a role for myeloablative regimens and research should focus on ways to reduce NRM in this setting. Disclosures: Gupta: Incyte: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees.

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Factors Influencing Long-Term Hematopoietic Function Following Autologous Stem Cell Transplantation

Blood ◽

10.1182/blood.v128.22.2186.2186 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2186-2186

Author(s):

Alissa Visram ◽

Natasha Kekre ◽

Christopher N. Bredeson ◽

Jason Tay ◽

Lothar B. Huebsch ◽

...

Keyword(s):

Stem Cell ◽

Board Of Directors ◽

Peripheral Blood ◽

Research Funding ◽

Infection Rates ◽

Advisory Committees ◽

Cd34 Cells ◽

Significant Difference

Abstract Background/Objective: Mobilized peripheral blood hematopoietic progenitor cells are the most common stem cell source for autologous hematopoietic stem cell transplantation (auto-HSCT). Successful short-term stem cell engraftment requires collection of at least 2x106 CD34+ cells/kg. The American Society of Bone Marrow Transplantation (ASBMT) recommends a stem cell infusion target of 3-5 x106 cells/kg (Giralt et al. 2014). However, the number of CD34+ cells to reinfuse to ensure long-term engraftment has not been established. Plerixafor, a reversible CXCR4 antagonist, increases CD34+ cell yield at collection even in patients who are predicted poor mobilizers (PPM). Although plerixafor could be used universally for all collections, this may not be the most cost-effective strategy (Veltri et al. 2012). This study sought to determine the minimum number of CD34+ cells/kg required for adequate long-term hematopoiesis, identify factors associated with poor long-term hematopoiesis, and determine if plerixafor mobilization improved long-term peripheral blood counts. Methods: A retrospective chart review was conducted on patients who underwent auto-HSCT between January 2004 and September 2013 at The Ottawa Hospital, for management of hematological malignancies. Peripheral blood cell counts were collected from 1 to 5 years after auto-HSCT, or until disease relapse. Poor long-term hematopoiesis was defined as an ANC <1 x109/L, hemoglobin <100 g/L, or platelets <100 x109/L. Patients were stratified into groups based on the infused CD34+ concentration (in cells/kg), and the proportion of patients with poor long-term hematopoiesis at 1, 2, 3, 4, and 5 years post auto-HSCT was compared with chi square tests. Long-term clinical outcomes (platelet and packed red blood cell transfusions, and post auto-HSCT infection rates) were compared between plerixafor-mobilized patients and PPM (defined as patients with pre-collection CD34+ <2 x 106 cells/kg) with standard mobilization regimens. Results: This study included 560 patients who underwent auto-HSCT, 210 with multiple myeloma and 350 with lymphoma. At 1 and 5 years post auto-HSCT 377 and 104 patients were included, respectively. A dose dependent improvement 1 year after auto-HSCT was seen in patients who received 0-2.99 x 106 CD34+ cells/kg (24.4%, n= 41) compared to patients who received 5-9.99 x 106 CD34+ cells/kg (11%, n=154, p=0.051) and ³10 x 106 CD34+ cells/kg (4.5%, n=66, p=0.006). Though there was a trend towards lower CD34+ infusions and poorer hematopoietic function (see table 1), there was no statistically significant difference in hematopoietic function based on CD34+ infusion concentrations after 1 year post auto-HSCT. 10 patients received <2 x106 CD34+ cells/kg, of whom the rate of inadequate hematopoiesis was 33% at 1 year (n=6) and 0% (n=1) at 5 years post auto-HSCT. Factors that increased the risk of poor hematopoiesis over the course of study follow up, based on a univariate analysis, included advanced age (OR 1.189, p=0.05), multiple prior collections (OR 2.978, p=0.035), and prior treatment with more than two chemotherapy lines (OR 2.571, p=0.02). Plerixafor-mobilized patients (n=25), compared to PPM (n=197), had a significantly higher median CD34+ cell collection (4.048 x109/L and 2.996 x109/L cells/kg, respectively, p=0.005). There was no significant difference in overall cytopenias, transfusion requirements, or infection rates between plerixafor-mobilized and PPM patients over the course of the study follow up. Conclusion: Low pre-collection CD34+ counts, advanced age, multiple prior collections, and more than two prior chemotherapy treatments adversely affected long-term hematopoiesis post auto-HSCT. We support the transfusion target of 3-5 x 106 cells/kg, as proposed by the ASBMT, given that at 5 years post auto-HSCT there was no statistical or clinically significant difference in hematopoietic function with higher CD34+ infusion targets. While mobilization with plerixafor significantly increased overall CD34+ cell collection when compared with PPM, long-term hematopoietic function and clinical outcomes were not different. This finding supports the practise of limiting plerixafor use only to patients who are PPM, thereby facilitating adequate stem cell collection and early engraftment, as opposed to universal plerixafor mobilization. Disclosures Sabloff: Lundbeck: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Canada: Membership on an entity's Board of Directors or advisory committees; Gilead: Research Funding; Alexion: Honoraria.

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Could Chronic Gvhd Overcome the Poor Prognosis of Patients with MDS and TP53 Undergoing Allogeneic HSCT?

Blood ◽

10.1182/blood.v126.23.2890.2890 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2890-2890

Author(s):

Juan Carlos Caballero ◽

Mercedes Sánchez-Barba ◽

Mónica Del Rey ◽

Kamila Janusz ◽

Eva Lumbreras ◽

...

Keyword(s):

Multivariate Analysis ◽

Stem Cell ◽

High Risk ◽

Board Of Directors ◽

Cumulative Incidence ◽

Research Funding ◽

Somatic Mutations ◽

Advisory Committees ◽

Poor Outcome

Abstract Background and Aim Although new agents have been approved for the treatment of MDS, the only curative approach for these patients is allogeneic hematopoietic stem cell transplantation (HSCT). Nevertheless, in these patients this approach has only obtained 40-60% of overall survival. Somatic mutations in MDS have recently been analyzed in order to confirm clonally and also prognostic impact in MDS patients. In this regard, TP 53 mutated gene is present in MDS in less than 10% of patients and is associated with advanced disease and high-risk features. Recent studies confirms poor outcomes in patients with TP 53 mutated receiving allogeneic stem cell transplantation1,2. The present study try to analyze if the development of chronic graft versus host disease (cGVHD) could modify, due to graft versus leukemia effect, the adverse prognosis of these high-risk patients (TP53 mutated patients). Design and Methods <>Results of HSCT in 92 MDS patients from 5 centers in Spain were retrospectively studied. Samples were collected 1 month prior to transplant. 280ng of the genomic DNA from BM cells was screened for somatic mutations in TP53 gene. The study was done by NGS on a GS Junior Instrument (Roche) according to an amplicon sequencing design. For each sample, eight exons (4-11) were amplified with preconfigured primer plates provided within the IRON II study network. Data analysis, were carried out using the Sequence Pilot software version 3.5.2 (JSI Medical Systems) and GS Amplicon Variant Analyzer software, versions 2.7 and 2.9 (Roche Applied Science). Minimum coverage of sequenced exons was 100 reads and the sensitivity of variant detection was set to a lower limit of >2% for bidirectional reads. Only those variants that resulted in amino acid change in the protein sequence were considered. OS and RFS were calculated using the Kaplan-Meier method. The log-rank test was used for comparisons. All calculations were done using SPSS 18.0. Cumulative incidence of relapse was also calculated by xlstat version 2014 program. <>Results Median age was 54 years (17-69), 71.7% were "de novo" MDS and regarding IPSS, 53% were in the int-2/high-risk category. Other characteristics were in Table 1. In the pre-transplant evaluation, 15 patients out of 92 (16,3%) were TP 53 mutated. The mutations were located in exons 5, 6, 7, 8 and 10. These variations were present in a variable percentageof the cell population (3 to 84%). All mutations were specific nucleotide changes except for two cases. At the time of the last update, 16 patients had relapsed (17.4%) and 40 had died (43.5%). After a median follow up of 15.5 months, OS was 56.5%. Median OS for patients with mutated TP53 trend a toward to be shorter than survival for patients without mutated TP53 (median of 7 mo vs median not reached, respectively, p=0.156). Multivariate analysis for OS confirmed complex karyotype (HR 5,588, 95CI 1,794-17,407, p=0.003) and no developement of cGVHD (HR 3,531, 95IC 1,634-7,632, p=0.001) as predictors for poor outcome. Cumulative incidence of relapse was 20.3% (+/-4.3%) at 1 years. Mutational status of TP53 significantly influenced on relapse (53.3% +/-12.9% vs 13.7% +/-4% at 1 year for patients with vs without TP 53 mutation (Gray test=0.001, Figure 2). Regarding Relapse Free Survival (RFS), after a median of follow up of 17 months, RFS was 67.9% and as previously suggested, the presence of TP 53 mutation had an impact on RFS (41.7% for mutated (median RFS of 6 months) and 75% for non mutated patients (median RFS not reached), p=0.009). Multivariate analysis for RFS confirmed age (HR 1.054, 95CI 1.005-1.106, p=0.032) and TP 53 mutated (HR 3.054, 95IC 1.145-8.149, p=0.026) as predictors for lower RFS. Regarding 15 patients with mutated TP 53, 7 did relapsed and 9 had died. Developement of cGVHD showed a trend toward to improve outcome among TP 53 mutated patients, with a better OS and RFS for those developing cGVHD as compared to those who did not (OS of 55% vs 17% for patients with and without cGVHD, p=0.039, Figure 2 and RFS of 71% vs 50%, respectively, p=0.3). <>Conclusions Mutated TP53 pre-allo patients presents poor outcome as compared to not mutated, as previously described Bejar1 and Kim2. Nevertheless, the developement of cGVHD could overcome the adverse impact of this factor due to the developement of graft versus tumor efect, improving survival curves (OS and RFS) as compared to previous published results. Study supported by GRS-1033/A/14 P53. 1.-BŽjar, JCO 2014, 32(25). 2.-Kim, BBMT 2015, Epub ahead of print. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures Sanz: JANSSEN CILAG: Honoraria, Research Funding, Speakers Bureau. Valcarcel:AMGEN: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; NOVARTIS: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CELGENE: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Díez-Campelo:CELGENE: Research Funding, Speakers Bureau; JANSSEN: Research Funding; NOVARTIS: Research Funding, Speakers Bureau.

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Incorporation of Thiotepa in a Reduced Intensity Conditioning Regimen Leads to Improved Engraftment after Stem Cell Transplant for Patients with Hemophagocytic Lymphohistiocytosis

Blood ◽

10.1182/blood-2019-132120 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3273-3273

Author(s):

Swati Naik ◽

Olive S. Eckstein ◽

Ghadir Sasa ◽

Robert A. Krance ◽

Carl E. Allen ◽

...

Keyword(s):

Stem Cell ◽

Board Of Directors ◽

Research Funding ◽

Graft Failure ◽

Unrelated Donor ◽

Advisory Committees ◽

Donor Chimerism ◽

Equity Ownership

Introduction: Hematopoietic stem cell transplantation (HSCT) for patients with hemophagocytic lymphohistiocytosis (HLH) following myeloablative conditioning regimens (MAC) is associated with high rates of non-relapse mortality. A previously reported prospective, phase 2 multi-center trial (RICHI) using using RIC strategy of fludarabine, melphalan and alemtuzumab (day -14) for HLH and primary immune deficiency syndromes (PIDS) demonstrated improved mortality rates but fewer than half the patients with HLH (41%) successfully engrafted without secondary graft failure, need for donor lymphocyte infusion (DLI) or second transplant. Incorporation of thiotepa during conditioning has been to shown to be safe and improve engraftment. We report the results of a retrospective analysis of nine consecutive patient treated with the inclusion of thiotepa into the RICHI backbone (RICHI+TT). Methods: Patients received a single additional dose of thiotepa 10mg/kg on day -3 added to the fludarabine/melphalan/alemtuzumab backbone (RICHI+TT) with the same graft-versus-host disease prophylaxis of methyprednisolone through day +28 and cyclosporine through day 180. To determine sustained engraftment, we used the same parameters the RICHI study defined as > 5 % donor chimerism without any intervention and alive at 1 year post-transplant. Results: Our cohort consisted of 8 males and 1 female with a median age of 7 years (range 1-18 years). Seven patients had HLH with proven pathogenic genetic mutations (biallelic PRF1 - 2, UNC13D - 2, STXBP1- 1, RAB27A-1, STAT3 gain of function-1), while the other 2 patients had HLH without identified pathogenic mutations (1- chronic active EBV, 1- juvenile idiopathic arthritis with refractory macrophage activation syndrome).The majority of patients received a bone marrow product (n = 8), one patient received a peripheral blood stem cell product; 6 patients received a graft from a matched related donor , two from a mismatched unrelated donor, and one from a matched unrelated donor. All patients engrafted at a median of 15 days post-transplant (8 patients at 100% donor chimera; 1 patient at 99% donor chimera at initial engraftment). Six of the 9 patients were evaluable to assess donor chimerism at 1 year as per study definitions with a median follow up of 875 days (range: 366 -1000 days). All 6 patients had > 5% donor chimerism and were alive at 1 year. Five of the 6 evaluable patients met criteria for sustained donor engraftment without need for intervention and all maintained 100% donor chimerism at last follow-up (Table 1). Only one of the six patients had evidence of falling donor chimerism; this stabilized at 40% donor chimerism after DLI. No patients had primary or secondary graft failure. Three patients were not evaluable for long-term assessment due to death prior to 1 year. Six of the 9 patients described here are alive and disease-free with stable long-term engraftment. The incorporation of Thiotepa to the RICHI backbone improved on previously reported sustained donor engraftment (Table 2). Conclusions: The RICHI+TT approach had better long-term donor engraftment with a decreased need for DLI or second transplant without increased rates of non-relapse mortality. Prospective studies are needed to determine the optimal treatment strategies for patients with HLH who require HSCT for cure. Disclosures Heslop: Cell Medica: Research Funding; Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Marker Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Kiadis: Membership on an entity's Board of Directors or advisory committees; Allovir: Equity Ownership; Gilead Biosciences: Membership on an entity's Board of Directors or advisory committees.

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High Rate of Long Term Complete Remission for Patients with Chronic Lymphocytic Leukemia (CLL) Who Relapse after Allogeneic Stem Cell Transplantation and Receive Salvage with Donor Lymphocyte Infusions (DLI)

Blood ◽

10.1182/blood.v128.22.5860.5860 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5860-5860

Author(s):

Alan P Skarbnik ◽

Mary E DiLorenzo ◽

Tracy Andrews ◽

Phyllis McKiernan ◽

Scott D. Rowley ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Board Of Directors ◽

Research Funding ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Disease Status ◽

Advisory Committees

Abstract Background: Allogeneic stem cell transplantation (SCT) remains the only curative option for CLL, in part due to allogeneic graft-vs-leukemia effect (GVL), which can lead to complete suppression of the CLL clone (Schetelig et al, JCO 2003). Management of post-SCT relapse remains challenging, and DLI has been successfully used as salvage, due to its potential to induce GVL (Delgado et al, Blood 2009). We evaluated outcomes of SCT for patients (pts) with a diagnosis of CLL transplanted at our center. Methods: 36 consecutive pts transplanted between 2004 and 2015 were reviewed. Kaplan Meier survival curves were produced to examine overall survival (OS), time to progression (TTP) and post-DLI survival. Univariate Cox Proportionate hazard models were also estimated to assess the impact of pt characteristics on the risk of survival and progression. Bivariate frequencies with Fisher exact tests, correlation analysis, and independent samples t-tests were performed to test associations across outcomes. Results: Sample was 72% male. Median age at time of SCT was 57 yo (range 42-74). Pts had a median time of 70 months (mos) between diagnosis (Dx) of CLL and SCT. Median follow-up post-SCT was 32 mos (range 1-118). Of the 30 pts with known disease status at the time of SCT, 16.7% were in complete remission (CR), 20% had stable disease (SD), 50% were in partial remission (PR) and 13.3% had progressive disease (PD). Median number of lines of therapy pre-SCT was 3 (range 1-8). Thirteen pts (36%) were refractory to their first line of therapy. 10 pts (27.8%) had del(17p), 11 pts (30.6%) had del(11q) and 8 pts (22.2%) had complex cytogenetics. Most patients (72%) received pre-SCT conditioning with FCR (Khouri et al, Exp Hematol 2004). 16 pts (44.4%) received rATG as part of their conditioning regimen. Graft-vs-host disease (GVHD) prophylaxis consisted of methotrexate and tacrolimus. 20 (55.6%) pts had acute GVHD and 19 (52.8%) had chronic GVHD. 5 (13.8%) pts had grade 3/4 acute GVHD and 1 (2.7%) had extensive chronic GVHD. When comparing pts who received SCT from unrelated donors (MUD, 24 pts) vs sibling donors (sib, 10 pts) there were no differences in rates of GVHD, disease progression or overall survival. Twenty-seven pts (75%) were in CR at first disease evaluation after SCT (CR conversion rate of 58.3%) and 2 pts (5.5%) had PD. On follow-up, another 15 pts (41.7%) presented PD. Median TTP was 14 months, with only 3 pts relapsing after 2 years from SCT. Eight pts who had PD and one patient who had a PR post-SCT received short-term anti-CLL therapy for disease debulking, followed by DLI. Six (66.6%) out of the 9 pts who received DLI achieved CR and are currently alive and in CR. Median follow-up post-DLI was 43 months and median duration of response to DLI was 47 mos (range 6-85 mos). Ultimately, 13 (36.1%) pts died, 8 (22.2%) were lost to follow-up, and 15 (41.7%) were alive at last contact. Disease progression was the most common cause of death (5 pts, 13.9%). Transplant-related mortality (TRM) was 13.9% (3 deaths due to infection, 2 deaths due to chronic GVHD). Only 2 deaths (5.5%) occurred during the first 100 days post-SCT, both due to infection. No deaths occurred due to acute GVHD. Median OS was 84 months. PFS (not accounting for pts who relapsed post-SCT but achieved CR with DLI) was 58% in the first year and 25% at five years. The median PFS was 19 months. Univariate and multivariate analysis of pre-SCT pt characteristics (age, time from Dx to SCT, number of therapies, stage, presence of adenopathy, MUD vs sib donor, cytogenetic abnormalities, ABO mismatch, disease status at SCT) did not show any statistically significant correlation with OS, PFS or GVHD rates. Conclusion: SCT remains the only curative option for CLL. Our experience shows that pts may achieve long-term survival with this approach. TRM was low (13.8%) and rates of acute and chronic GVHD were compatible with previous reports (Sorror et al, JCO 2005; Dreger et al, Blood 2010). Type of donor (MUD vs sib) did not impact outcomes, suggesting that patients without a matched sibling should not be denied transplantation if a MUD is available. Although 47% of the patients eventually progressed after transplantation, 66% of patients who received DLI for salvage were able to achieve CR and remain progression-free for a prolonged period of time, underlining the importance of the GVL effect. Most relapses occurred within the first 2 years post SCT and late relapses were rare. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures Skarbnik: Gilead Sciences: Speakers Bureau; Seattle Genetics: Speakers Bureau; Genentech: Speakers Bureau; Abbvie: Consultancy; Pharmacyclics: Consultancy. Vesole:Celgene: Speakers Bureau; Takeda: Speakers Bureau; Janssen: Speakers Bureau; Amgen: Speakers Bureau; Novartis: Speakers Bureau. Goy:Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Writing support, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Feldman:Pharmacyclics: Speakers Bureau; Celgene: Speakers Bureau; Seattle Genetics: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau. Leslie:Seattle Genetics: Speakers Bureau; Celgene: Speakers Bureau. Leslie:Seattle Genetics: Speakers Bureau; Celgene: Speakers Bureau.

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The Interaction between IPSS Score and JAK2 Mutation Identifies Patients at Different Vascular Risk in Primary Myelofibrosis

Blood ◽

10.1182/blood-2021-145116 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 236-236

Author(s):

Tiziano Barbui ◽

Arianna Ghirardi ◽

Alessandra Carobbio ◽

Arianna Masciulli ◽

Greta Carioli ◽

...

Keyword(s):

Risk Factors ◽

Multivariate Analysis ◽

Board Of Directors ◽

Research Funding ◽

Primary Myelofibrosis ◽

Vascular Risk ◽

Advisory Committees ◽

Jak2 Mutation ◽

Thrombosis Rate

Abstract BACKGROUND The rate of major arterial and venous thrombosis in primary myelofibrosis (PMF) and post-ET (PET) and post-PV (PPV) secondary myelofibrosis has been evaluated in a limited number of studies. In the present paper we describe the clinical epidemiology of thrombosis in a large series of patients with overt PMF and PPV/PET MF looking at the rate and risk factors. Moreover, we report findings on thrombosis rate in two cohorts of patients treated with Hydroxyurea (HU) or Ruxolitinib (Ruxo). METHODS Patients were registered in the European Registry for Myeloproliferative Neoplasms (ERNEST). This project, promoted by the European LeukemiaNet, is coordinated by FROM - Foundation for Research, Papa Giovanni XXIII Hospital, Bergamo (Italy) and supported by Novartis through a research collaboration . Patients were diagnosed in 6 Centers from Italy, Spain and Sweden, between Jan, 2001 and Dec, 2012, with the required follow-up information. Patients (n= 1010) with PMF (n=584, 59%), PET-MF (n=207, 20%) and PPV-MF (n=219, 21%) were evaluated for incident thrombosis as primary endpoint. Considering death as a competitive event, uni-and multivariate analyses were performed by applying Fine & Gray competing-risk regression models. RESULTS After a median follow-up of 3.8 years (IQR: 1.8-7.1) from diagnosis, 108 thromboses (10.7%) occurred, for an overall incidence rate of 2.0% pts-yr (95% CI: 1.7-2.5). Arterial thromboses were found in 50 patients (46.3%) including cerebral (n=21, 19.4%), myocardial infarction (n=13, 12.0%) and peripheral events (n=9, 8.3%). Venous thromboses were 58 (53.7%), of which 25 (23.0%) were DVT ± PE and 11 (10.2%) were splanchnic. Thrombosis rate was 1.91, 1.60 and 2.79% pts-yr in PMF, PET-MF and PPV-MF, respectively. In univariate analysis, factors significantly associated with an increased thrombotic risk in PMF were age (p=0.013) and the presence of the JAK2 mutation (p=0.003); in addition, a significant higher proportion of PMF patients at low and intermediate-1 vs intermediate-2 or high risk IPSS score, had thrombosis during the follow-up (p=0.008). In multivariate analysis, only JAK2 mutation retained statistical significance (SHR=3.12, 95% CI: 1.40-6.94, p=0.005). Conversely, neither in univariate nor in multivariable analysis, significant risk factors were not found.To investigate the possible interaction of IPSS score and JAK2 mutation we created a model whose results are presented in Fig. 1A: the cumulative incidence function (CIF) of thrombosis was significantly lower in patients with JAK2 wild-type and intermediate-2 or high IPSS score (CIF: 4% projected at 10 years; SHR=1 [reference category]), while patients at the highest risk for thrombosis harbored JAK2 mutation and were categorized at low or intermediate-1 by IPSS score (CIF: 20% projected at 10 years, SHR=7.13, p=0.008). Of note, thrombosis had a significant impact on mortality. After adjusting for sex, age, year of diagnosis, type of MF and IPPS, HR was 1.51, (95% CI. 1.15-1.98, p=0.003).The influence of drug exposure to incident thrombosis was investigated in two cohorts of 559 consecutive patients exposed to HU (n=470) or to Ruxo (n=89), median treatment 2.6 and 3.0 years, respectively. HU- compared to Ruxo-treated patients were older (median age 67 vs. 63 years, p=0.001), more frequently triple negatives (12% vs. 2%, p=0.036), less splenomegalic (spleen length >10 cm: 30% vs. 88%, p <.001) and less symptomatic (49% vs. 79%, p=0.031). Of note, median time from MF diagnosis to therapy start in Ruxo group was 4 years, whereas patients started HU at MF diagnosis. In 56 of 89 Ruxo-treated patients (62.9%), the drug was given after a prior HU therapy. The thrombosis rate from the time of initiation of therapy was 2.40% pts-yr (95% CI 1.78-3.24) under HU and 1.28% pts-yr (95% CI 0.48-3.41) under Ruxo (CIF curves in Fig. 1B). In multivariate analysis corrected for MF type, DIPPS at first drug administration, JAK2 mutation and time from MF diagnosis, exposure to Ruxo showed a non-significant trend towards a protection of approximately 70% compared to HU (SHR=0.33, 95% CI: 0.08-1.32, p=0.117). CONCLUSION IPSS score, in addition to the survival risk assessment, may be useful, if associated with the JAK2 mutation, to recognize patients at vascular risk and to suggest appropriate anti-thrombotic prophylaxis. The trend towards a benefit of Ruxo, compared to HU, warrants a study in larger case series. Figure 1 Figure 1. Disclosures Barbui: AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Passamonti: Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Speakers Bureau. Vannucchi: Incyte: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Lectures; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Lectures; AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: Lectures.

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Multidimensional Vascular Evaluation in Patients Treated with Tyrosine Kinase Inhibitors (TKIs): From Plaque Formation to Evolution and Follow up on 150 Patients

Blood ◽

10.1182/blood-2020-142732 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 54-54

Author(s):

Elisabetta Abruzzese ◽

Rossana Gloria ◽

Andrea Siani ◽

Carla Mazzone ◽

Matteo Molica ◽

...

Keyword(s):

Risk Factors ◽

Heart Disease ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Board Of Directors ◽

Surgical Intervention ◽

Control Group ◽

Advisory Committees

Background Among the unresolved issues concerning management of chronic myeloid leukemia (CML) patients, the most feared are long-term adverse events due to TKI treatment. Although TKIs have revolutionized CML outcomes, their use has also been associated with severe side effects including cardiovascular events, of which peripheral arterial occlusive disease (PAOD) is the most frequently reported. In 2010 we began a long-term collaboration with local angiologists and vascular surgeons to investigate, screen and follow patients on TKI therapy. Placque formation, evolution and follow up of 150 patients were studied and are presented here. Methods We analyzed 143 CML and 7 Ph+ Acute Lymphoid leukemia (ALL) patients, all of whom were treated with TKIs. Careful assessment of cardiovascular risk factors (i.e., age, smoking, obesity, diabetes, high blood pressure, high LDL or low HDL cholesterol levels, family history of heart disease or other cardiovascular disease) were done according to the European Society of Cardiology Systematic Coronary Risk Evaluation (SCORE) risk charts. A complete vascular screening, including physical examination, and a series of instrumental tests were performed for all patients. Tests included doppler echocardiography (US) of supra-aortic arteries with measurement of pre-bulbar IMT, abdominal arteries and inferior limbs arteries and veins (IL), ABI of the posterior tibial artery and digital photoplethysmography (FPG). Patients needing surgical intervention were referred to a surgeon. The team of hematologists, angiologists and surgeons met periodically to discuss results and intervention approaches. Results Patients included 76 males and 74 females with a median age of 53.7 yo (range 18-85). All patients were treated with a TKI at diagnosis, 87 (58%) with imatinib, 63 (42%) with other TKIs, including ponatinib (2 LLA), and all received TKI therapy for a minimum of 12 months since 2010. For analyses purposes, patients were divided in 7 different age groups at diagnosis (18-30, 31-40, 41-50, 51-60, 61-70, 71-80 and 81-85 years; patients incidence per group was 6%, 18%, 18.6%, 27.4%, 13.3%, 12.7% and 4%, respectively). Each patient in the study received yearly screening, and this increased to every 3-6 mo if abnormalities occurred. Of the 150 patients in the study, 10 (7%) developed severe PAOD (grade 3-4) requiring revascularization. Districts involved were: carotid (5), renal (2) and extremities (14 IL, 1 subclavian). Three patients were polyvascular requiring intervention in multiple regions. 18 patients with no malignancies requiring surgery were used as a control group and matched for sex, age, diabetes, smoking, district and intervention to compare patency rates, morbidity and mortality. At event, these 10 patients were taking imatinib (1), bosutinib (1), nilotinib (5) and ponatinib (3). None of them had a previous PAOD, but all had cardiovascular risk factors (100% were hypertensive). Median age was 66.8 yo (range 46-82) and the median number of PAOD risk factors (age >60, hypertension, diabetes, male gender, nicotine abuse and coronary heart disease) was 2 (range 1-5). Plaque was deemed significant when stenosis was >30%; at this point it developed very rapidly, with signs of arterial thrombosis within a year, requiring intervention. IMT scores (measuring thickness of carotid artery wall) and ABI followed by FPG and their variation over time proved predictive for plaque evolution. No patient died due to complications relating directly to surgical intervention or within 30 days post-surgery. One patient required a major limb amputation at 12 months. Patency rates were similar in the TKI and control group at 12 months (88.2% vs 80%), however the frequency of reintervention (endo or open) was 50% in TKI patients (n=5) and 11% in the control group (n=2; P<0.01). Discussion Multidisciplinary evaluation, comorbidity analysis and cardiovascular risk assessment in CML patients are highly recommended, at diagnosis if possible, to implement a tailored treatment strategy and to identify patients who require strict monitoring of risk factors during treatment. Extensive and detailed information on the 150 patients in this study will be presented with a focus on the onset and characteristics of thrombotic arterial events, medical/surgical interventions, analysis of instrumental parameters (ABI, IMT, FPG) and correlation with clinical data. Disclosures Abruzzese: Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bms: Honoraria.

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Allogeneic Stem Cell Transplantation Is Associated with Long Term Disease Control in Chemo Sensitive Follicular Lymphoma Patients

Blood ◽

10.1182/blood.v118.21.2024.2024 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2024-2024

Author(s):

Auro Viswabandya ◽

Tony Panzarella ◽

Dennis Dong Hwan Kim ◽

Vikas Gupta ◽

Jeffrey H. Lipton ◽

...

Keyword(s):

Stem Cell ◽

Follicular Lymphoma ◽

Disease Control ◽

Board Of Directors ◽

Acute Gvhd ◽

Unrelated Donor ◽

Matched Unrelated Donor ◽

Advisory Committees

Abstract Abstract 2024 Introduction: Follicular lymphoma (FL) remains an incurable disease despite the use of immunochemotherapy or autologous stem cell transplant (ASCT). Allogeneic stem cell transplantation (Allo-SCT) remains a viable treatment option in FL because of its associated graft versus lymphoma effect and potential to achieve long term disease control. There is limited data in literature regarding long term outcome of follicular lymphoma post allo-SCT. Patients and Methods: We identified a total of 52 patients with chemosensitive FL underwent allo-SCT at our centre between 1989 and 2009. 89% were in a chemosensitive remission at time of transplantation. The conditioning regimens included BUCY in 48 (92%) patients. GVHD prophylaxis was cyclosporine and methotrexate until 2009 and subsequently cyclosporine and mycophenolate mofetil. Patients undergoing matched unrelated donor (MUD) transplant received alemtuzumab. Results: There were 30 (58%) males and 22 (42%) females. The median age at BMT was 45 years (range:24–64) and the median number of prior chemotherapy regimens was 3 (range: 1–6). Fifteen (29%) of patients had only received <3 prior lines of chemotherapy while 36 (69%) had received more than 3 or more lines of therapy at time of transplantation. Prior chemotherapy regimens included anthracyclines in 46 (88%), platinum in 25 (48%), chlorambucil in 25 (46%) and purine analogues in 15 (29%). Twenty three (44%) patients had received prior rituximab and 11 (21%) had received prior radiation therapy (RT). Three (6%) patients had prior ASCT. The median time from diagnosis to transplant was 35 months (range 6–148). All transplants were myeloablative except for one reduced intensity conditioning (RIC) transplant. Forty-five (87%) of patients received matched related donor transplant whereas 2 (4%) received matched unrelated donor (MUD) transplant with the remainder being mismatched donor transplants. The graft source was bone marrow in 35 (67%) and peripheral blood stem cells in 16 (31%). Grade 1–2 acute GVHD was seen in 58% and grade 3–4 in 12%. Chronic GVHD was observed in 50% patients. There was a statistically significant higher incidence of acute GVHD in those who received BM versus PBSC as the graft source although the incidence of cGVHD was not different. Three (6%) patients had relapsed at a median follow up of 68 months. The median time to relapse post-BMT was 54 months (range: 13 – 94). At a median follow up of 68 months (all patients) and 94 months (those who are alive); 34 (65%) patients are alive and well. None relapse mortality was 30%. The overall survival (OS) of entire cohort at 60 months was 70% (Fig-1) and PFS was 68%. Patients, who had achieved chemosensitivity pre transplant, had statistically significant PFS (p=0.04) and OS (p=0.02). In multivariate analysis, number of chemotherapy regimens (</=2) was associated with improved OS (p=0.05). Conclusions: In summary, myeloablative allo-SCT in younger patients with chemosensitive FL has excellent potential for long-term disease control. With a median follow-up in survivors of 94 months, the NRM remains reasonable. Given inferior results in multiply treated patients, future strategies should identify high risk groups that should be considered for allo-SCT based strategies. Disclosures: Gupta: Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

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