A Clinical Review of the Co-Occurrence of Myeloproliferative and Lymphoproliferative Neoplasms

Abstract The co-occurrence of myeloproliferative (MPN) and lymphoproliferative neoplasms (LPN) is rare and many publications have been limited to small case reports. Others have involved a considerable number of patients, but the coexistence remains underreported and inadequately studied. A recent retrospective review reported that a MPN patients have a 2.8-fold higher relative risk of developing LPN. A database developed at Weill Cornell Medicine (WCM) was queried for patients with ≥3 visits between 1998-2018 with a diagnostic code for a MPN and lymphoma or myeloma subtype. Patients identified were verified to ensure that study inclusion criteria were satisfied. Observed co-occurrence was compared to nation-wide reported prevalence. Demographic and clinical details of 24 patients with a MPN and LPN were recorded (Table 1). The ratio of males to females was 1.7. Essential thrombocythemia and polycythemia vera, and chronic lymphocytic leukemia (CLL) were the leading MPN and LPN subtypes, respectively. Patients were assigned to risk or staging categories at diagnosis based on subtype-specific criteria (Table 2). Median values for diagnostic bone marrow biopsy findings in 14 patients were 2% [0-5] for myeloblasts and 80% [15-100] for cellularity. Additionally, 10 patients had evaluated reticulin fibrosis: 5 (50.0%) presented as MF-0, 4 (40.0%) as MF-1, and 1 (10.0%) as MF-2. Progression to myelofibrosis was confirmed by morphology in 1 (4.2%) patient 10.1 years after a polycythemia vera diagnosis and 5.4 years after a diffuse large B-cell lymphoma (DLBCL) diagnosis. Progression to acute myeloid leukemia was confirmed by morphology in 1 (4.2%) patient 2.4 years after a chronic myelomonocytic leukemia diagnosis and 1.2 years after a smoldering myeloma (SM) diagnosis. Interphase fluorescence in situ hybridization (iFISH) detected cytogenetic abnormalities in 5/8 (62.5%) CLL patients: 2/5 (40.0%) and 5/5 (100.0%) patients harbored deletions in trisomy 12 and 13q14, respectively. Immunoglobulin heavy chain variable region gene (IGVH) status was unmutated in 2 (25.0%) patients. One (12.5%) patient was CD38+ and 2/6 (33.0%) patients were ZAP-70+. At diagnosis, all 8 patients presented with early stage disease (Rai stage 0-II). Based on the CLL-specific international prognostic index (IPI), 3/8 (37.5%) and 5/8 (62.5%) presented as low-risk and intermediate-risk, respectively. Of the 6 lymphoma patients: 5 (83.0%) patients presented with Ann Arbor stage-IV disease at diagnosis. Four (66.7%) patients presented as low/intermediate-risk, and 2 (33.3%) presented as high-risk based on disease-specific IPIs. One patient presented with -17p by iFISH. All 4 patients that were evaluated for Ki-67 had moderate/high expression. Of the 7 multiple myeloma (MM) patients, 6 (85.7%) presented as stage 1 and 1 (14.3%) as stage 3. Of the 3 SM patients, all 3 presented as low risk [12]. In addition, these patients were categorized as IgG-K (4; 40.0%), IgG-L (2; 20.0%), IgA-K (1; 10.0%), IgA-L (1; 10.0%), IgM (1; 10.0%), and biclonal IgG-L/IgA-L (1; 10.0%) [13]. Mutation statuses were identified by commercially tested myeloid or lymphoid molecular panels. As expected in this MPN subtype distribution, 11 (45.8%) are JAK2+, 2 (8.3%) are MPL+, 1 (4.2%) is BCR-ABL+, and 1 (4.2%) is CALR+ (Table 3). The risk of a co-occurrent MPN and LPN is higher than expected if they are mutually exclusive (Table 4A-4B, 5). Of interest, 13 (54.2%) patients were diagnosed with a MPN 11.8±18.8 years prior to a LPN; conversely, 11 (45.9%) were diagnosed with a LPN 6.5±6.2 years prior to a MPN. In addition, MPN therapy was started 2.0±2.3 years after a MPN diagnosis, and LPN therapy was started 2.6±4.0 years after a LPN diagnosis. A review of survival analysis requires larger subtype populations since the degree of survival can vary greatly, but it has been reported that patients with a MPN or LPN have significantly reduced life expectancy when compared to the general population. Median follow-up for our patient is 8.2 years (1.5-28.0) with 17/24 (70.8%) patients still being actively followed at our institution, 6 (25.0%) are been lost to follow-up, and 1 (4.2%) is deceased. The significant prevalence of these hematologic malignancies in combination emphasizes the importance of performing a bone marrow biopsy, which we espouse at our institution, cytogenetic analysis, and myeloid and lymphoid molecular testing to identify mutations. Disclosures Furman: Loxo Oncology: Consultancy; Gilead: Consultancy; Verastem: Consultancy; Acerta: Consultancy, Research Funding; TG Therapeutics: Consultancy; Incyte: Consultancy, Other: DSMB; Pharmacyclics LLC, an AbbVie Company: Consultancy; Genentech: Consultancy; Sunesis: Consultancy; Janssen: Consultancy; AbbVie: Consultancy. Niesvizky:Amgen Inc.: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Ritchie:Bristol-Myers Squibb: Research Funding; Novartis: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; Astellas Pharma: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Other: Travel, Accommodations, Expenses, Speakers Bureau; Pfizer: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; ARIAD Pharmaceuticals: Speakers Bureau.

Download Full-text

90Y-Ibritumomab Tiuxetan Followed by Rituximab Is a Safe Treatment Option for Relapsed or Refractory Diffuse Large B-Cell Non-Hodgkin s Lymphoma

Blood ◽

10.1182/blood.v116.21.2866.2866 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2866-2866

Author(s):

Katarina Luptakova ◽

Michelle Kim ◽

Pamela Ely ◽

Barbara Grant ◽

John Anthony Parker ◽

...

Keyword(s):

Bone Marrow ◽

B Cell ◽

Research Funding ◽

Bone Marrow Involvement ◽

B Cell Lymphoma ◽

First Line ◽

Ibritumomab Tiuxetan ◽

Baseline Platelet Count ◽

Large B Cell

Abstract Abstract 2866 Introduction: Diffuse large B cell lymphoma (DLBCL) is the most common lymphoid malignancy and is generally responsive to anthracycline-containing chemotherapy. However, 60% of patients (pts) will relapse after their first line treatment. At the time of relapse the only curative approach includes the use of a stem cell transplant (SCT). The incidence of DLBCL increases with age which creates a subset of pts who are not candidates for first line anthracycline-based chemotherapy, and a large subset of pts who are not candidates for SCT due to advanced age and/or co-morbidities. Thus, there is a significant unmet need for therapies with a low toxicity profile in elderly or medically unfit pts with DLBCL. 90Y-ibritumomab tiuxetan (90Y-IT) is an anti-CD20 murine antibody linked with a beta-emitting isotope approved for use in indolent lymphoma. Maintenance rituximab (R) has been reported to increase response rates and prolong remission duration in some lymphomas. We performed a phase II multicenter clinical trial to examine the efficacy of 90Y-IT induction followed by maintenance R in pts with DLBCL. Patients and Methods: Eligible pts were either intolerant of anthracycline-based chemotherapy or had relapsed or refractory CD20+ DLBCL with measurable disease. Pts had to be ineligible for SCT for reasons other than failure to harvest stem cells. Bone marrow involvement by lymphoma of less than 25% based on bilateral bone marrow aspirate and biopsy was required. R 250 mg/m2 was administered IV immediately followed by 111In-ibritumomab tiuxetan. Nuclear scans were performed at 24 and 48 hours to insure there was no altered biodistribution. On day 8 a second infusion of R 250 mg/m2 followed by 0.4 mCi/kg (for pts with a baseline platelet count >150,000/mm3) or 0.3 mCi/kg 90Y-IT (for pts with a baseline platelet count 100,000-149,000/mm3) was given. Pts with multiple extranodal sites or prior bone marrow involvement received CNS prophylaxis with intrathecal methotrexate or cytarabine. Maintenance R 375 mg/m2 was given on weeks 3–6, then weekly × 4 every 6 months × 4 cycles or until progression. Results: Between 10/2003 and 9/2009, 25 pts have been treated. During the course of the study, the ownership of the therapeutic agent changed three times and therefore enrollment was interrupted on two occasions. The median age of pts was 79 (range 45–91), 36% pts had a sIPI score 3 or more. The median number of prior regimens is 2 [0-5]. The 90Y-IT treatment regimen produced an overall response rate of 36% [9 pts] with 28% CR [7 pts]. To date, the mean OS is 18 months (median 8.1 months) with a median follow-up of 11.2 months. Among responding pts, the median OS has not been reached with a median follow-up of over 26.2 [0.1-71.4] months. Thirteen pts died within the first year, 6 patients (24%) continue to be in remission greater than 18 months, and 4 patients (16%) remain in long-term remission [39.9-71.4 months]. The most frequently observed toxicity was hematologic. Eleven percent of pts had grade 4 neutropenia with only one patient experiencing febrile neutropenia, and 16% of pts experienced grade 4 thrombocytopenia. There were no unexpected non-hematologic toxicities except for 1 patient that experienced extravasation. One late-occurring case of MDS/AML was reported that is possibly related to the study regimen, and one case of adenocarcinoma of the GI tract that is likely unrelated. Of note, none of the pts that progressed on the chemotherapy preceding this study achieved a response to the study regimen. Conclusions: The 90Y-IT treatment regimen has an acceptable toxicity profile in elderly or heavily pretreated pts with DLBCL. The two week outpatient 90Y-IT infusion produces response rates and durations similar to that of more prolonged cytotoxic chemotherapy regimens. Progression on previous chemotherapy predicts for poor response to 90Y-IT. Treatment with 90Y-IT can provide durable remission to a select subset of pts who are not candidates for SCT, or intensive anthracycline based chemotherapy. Disclosures: Off Label Use: We are describing a phase II study of the use of 90Y-Ibritumomab Tiuxetan for treatment of diffuse large B-cell lymphoma. Current FDA approved use of 90Y-Ibritumomab Tiuxetan includes relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL) or previously untreated follicular NHL who achieve a partial or complete response to first-line chemotherapy. Joyce:Spectrum Pharmaceuticals, Inc.: Research Funding; Cell Therapeutics Inc: Research Funding; Biogen Idec: Research Funding.

Download Full-text

Application of a Validated Predictive Model for Venous Thromboembolism in Cancer to Patients with Multiple Myeloma

Blood ◽

10.1182/blood.v128.22.534.534 ◽

2016 ◽

Vol 128 (22) ◽

pp. 534-534

Author(s):

Natasha Catherine Edwin ◽

Jesse Keller ◽

Suhong Luo ◽

Kenneth R Carson ◽

Brian F. Gage ◽

...

Keyword(s):

High Risk ◽

Research Funding ◽

Risk Group ◽

High Risk Group ◽

Low Risk ◽

Intermediate Risk ◽

Discriminative Ability ◽

Blood Institute ◽

C Statistic

Abstract Background Patients with multiple myeloma (MM) have a 9-fold increased risk of developing venous thromboembolism (VTE). Current guidelines recommend pharmacologic thromboprophylaxis in patients with MM receiving an immunomodulatory agent in the presence of additional VTE risk factors (NCCN 2015, ASCO 2014, ACCP 2012). However, putative risk factors vary across guidelines and no validated VTE risk tool exists for MM. Khorana et al. developed a VTE risk score in patients with solid organ malignancies and lymphoma (Blood, 2008). We sought to apply the Khorana et al. score in a population with MM. Methods We identified patients diagnosed with MM within the Veterans Health Administration (VHA) between September 1, 1999 and December 31, 2009 using the International Classification of Diseases (ICD)-03 code 9732/3. We followed the cohort through October 2014. To eliminate patients with monoclonal gammopathy of undetermined significance and smoldering myeloma, we excluded patients who did not receive MM-directed therapy within 6 months of diagnosis. We also excluded patients who did not have data for hemoglobin (HGB), platelet (PLT) count, white blood count (WBC), height and weight, as these are all variables included in the Khorana et al. risk model. Height and weight were assessed within one month of diagnosis and used to calculate body mass index (BMI). We measured HGB, PLT count, and WBC count prior to treatment initiation: within two months of MM diagnosis. A previously validated algorithm, using a combination of ICD-9 code for VTE plus pharmacologic treatment for VTE or IVC filter placement, identified patients with incident VTE after MM diagnosis (Thromb Res, 2015). The study was approved by the Saint Louis VHA Medical Center and Washington University School of Medicine institutional review boards. We calculated VTE risk using the Khorana et al. score: We assigned 1 point each for: PLT ≥ 350,000/μl, HGB < 10 g/dl, WBC > 11,000/μl, and BMI ≥ 35 kg/m2. Patients with 0 points were at low-risk, 1-2 points were considered intermediate-risk and ≥3 points were termed high-risk for VTE. We assessed the relationship between risk-group and development of VTE using logistic regression at 3- and 6-months. We tested model discrimination using the area under the receiver operating characteristic curve (concordance statistic, c) with a c-statistic range of 0.5 (no discriminative ability) to 1.0 (perfect discriminative ability). Results We identified 1,520 patients with MM: 16 were high-risk, 802 intermediate-risk, and 702 low-risk for VTE using the scoring system in the Khorana et al. score. At 3-months of follow-up, a total of 76 patients developed VTE: 27 in the low-risk group, 48 in the intermediate-risk group, and 1 in the high-risk group. At 6-months of follow-up there were 103 incident VTEs: 41 in the low-risk group, 61 in the intermediate-risk group, and 1 in the high-risk group. There was no significant difference between risk of VTE in the high- or intermediate-risk groups versus the low-risk group (Table 1). The c-statistic was 0.56 at 3-months and 0.53 at 6-months (Figure 1). Conclusion Previously, the Khorana score was developed and validated to predict VTE in patients with solid tumors. It was not a strong predictor of VTE risk in MM. There is a need for development of a risk prediction model in patients with MM. Figure 1. Figure 1. Disclosures Carson: American Cancer Society: Research Funding. Gage:National Heart, Lung and Blood Institute: Research Funding. Kuderer:Janssen Scientific Affairs, LLC: Consultancy, Honoraria. Sanfilippo:National Heart, Lung and Blood Institute: Research Funding.

Download Full-text

A Retrospective Multicenter Case Study Evaluating the Characteristics, Management and Outcome of Acquired Amegakaryocytic Thrombocytopenia

Blood ◽

10.1182/blood-2021-153388 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3167-3167

Author(s):

Anais Roeser ◽

Guillaume Moulis ◽

Mikael Ebbo ◽

Louis Terriou ◽

Elsa Poullot ◽

...

Keyword(s):

Bone Marrow ◽

Platelet Count ◽

Aplastic Anemia ◽

Board Of Directors ◽

Bone Marrow Biopsy ◽

Research Funding ◽

Advisory Committees ◽

Overall Response ◽

Acquired Amegakaryocytic Thrombocytopenia

Abstract Introduction Acquired amegakaryocytic thrombocytopenia (AAT) is an extremely rare disease characterized by acquired megakaryocytic aplasia or hypoplasia with no other lineage abnormalities. Given limited evidence, the first aim of this study was to describe the characteristics, management and outcome of patients with AAT, the second aim was to examine the therapeutic response through a systematic review of published case reports. Patients and Methods We carried out a retrospective multicenter study through the French Reference Network for Adult Autoimmune Cytopenias, including patients aged > 18 years with acquired thrombocytopenia with a platelet count < 50 x 10 9/L, associated with a megakaryocytes / granulocytes ratio < 50 % on bone marrow, diagnosed from July 2007 to February 2020. Exclusion criteria were: abnormal granular lineage, evidence of dysplasia, bone marrow infiltration by tumor cells or hematologic malignancy, significant karyotype abnormality, and significant paroxysmal nocturnal hemoglobinuria clone. Bone marrow biopsy were centrally reviewed. Patients' medical charts were collected using the standardized form of the referral center for adult immune thrombocytopenia (ITP). Response to treatment was defined according to standardized international criteria for ITP: response (R) and complete response (CR) were respectively defined as platelet count of > 30 × 10 9/L with at least a doubling of the baseline value, and platelet count of > 100 × 10 9/L ; overall response as either R or CR. We performed a systematic review conducted through Medline and Scopus databases from 1970 to April 2021. Cases were included in the analysis if initial platelet count was < 50 x 10 9/L and bone marrow examination was available, demonstrating a megakaryocyte hypoplasia or aplasia with no alternate diagnosis. Results We screened 23 patients reported as thrombocytopenia with absence or decreased megakaryocytes. Eleven patients were excluded because of: presence of megakaryocytes on bone marrow biopsy despite megakaryocytic aplasia on bone marrow aspirate (n=2), absence of bone marrow biopsy (n=4), aplastic or hypoplastic bone marrow (n=3), moderate thrombocytopenia > 50 x 10 9/L (n=1), lack of data (n=1). Twelve patients were included in the analysis. AAT patients had a median age of 52.5 years, 5/12 (41.7%) were female, 6/12 (50%) had a preexisting autoimmune disease (Table 1). All bone marrow biopsies reviewed to date contained CD8+ T-cell infiltrates. Eight patients received a first line treatment with corticosteroids and/or intravenous immunoglobulins (IVIg), a single response was observed. Ten patients received cyclosporine in monotherapy resulting in 4CR, and 1R or in combination with diverse agents with heterogenous responses. Six had received a single therapy with thrombopoietin receptor agonists (TPO-RAs) inducing 4 CR. Eventually, 9 patients (75%) achieved a CR under therapy, obtained with ciclosporin alone in 3 cases, ciclosporin in association with TPO-RA or ATG in 2 cases, cyclophosphamide followed-up by mycophenolate mofetil in 1 case, and TPO-RAs alone in 4 patients (of whom 3 had previously received at least on immunosuppressive therapy). After a median follow up time of 4.0 years (range 1.2 - 11.9), 2 (16%) patients eventually developed an aplastic anemia, 7 and 41.5 months respectively after initial AAT diagnosis. The literature search yielded 108 articles, of which 75 articles reporting 85 cases were included in the final analysis. The pooled analysis of newly reported and historic cases included 97 cases. Overall response rates to corticosteroids and IVIg were respectively 22.4 % and 5.3 % (Table 2). Ciclosporin was used as single agent in 37.1 % of patients, with an overall response rate of 66.7 %. TPO-RAs were used in 9 cases, with a CR in 7 patients (77.8%). Overall, 9/97 patients (9.3 %) experienced an aplastic anemia during the follow-up. The presence of a thymoma was associated with a higher risk of aplastic anemia (OR 6.83 (95%CI 1.22-34.00, p=0.020)). Conclusion Distinguishing AAT from ITP is of significance as the outcome and response to therapy strongly differ. Aplastic anemia may occur in the follow-up but remain rare. Corticosteroids and IVIg are inefficient in most cases, ciclosporin appear to be very effective, TPO-RA could also be an option, as single therapy or in associations. Further data will be needed to define the respective place of these treatments. Figure 1 Figure 1. Disclosures Moulis: Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Argenix: Membership on an entity's Board of Directors or advisory committees; Grifols: 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; Sobi: Membership on an entity's Board of Directors or advisory committees. Ebbo: Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees; Octapharma: Other: Attendance Grant; Amgen: Honoraria; Sobi: Other: Attendance Grant; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Terriou: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Haioun: Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; Servier: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Miltenyi: Honoraria, Research Funding. Michel: Amgen,Novartis,UCB,Argenx,Rigel: Honoraria. Godeau: Amgen: Consultancy; Novartis: Consultancy; Grifols: Consultancy; Sobi: Consultancy. Mahevas: GSK: Research Funding; Amgen: Honoraria.

Download Full-text

Low Von Willebrand Factor: Cut-Off Value for Diagnosis and Risk Score to Predict Bleeding Incidence

Blood ◽

10.1182/blood-2020-142375 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 18-19

Author(s):

Ferdows Atiq ◽

Esmee Wuijster ◽

Moniek P.M. de Maat ◽

Marieke J.H.A. Kruip ◽

Marjon H. Cnossen ◽

...

Keyword(s):

High Risk ◽

Risk Score ◽

Research Funding ◽

Low Risk ◽

Intermediate Risk ◽

Spontaneous Bleeding ◽

High Risk Patients ◽

Risk Patients ◽

Surgical Bleeding

Introduction Although large studies have recently provided valuable insights on the diagnosis, bleeding phenotype, and treatment outcomes of VWD patients, these aspects remain poorly understood in individuals with low VWF. Firstly, there is no clear evidence which cut-off value should be used to diagnose low VWF. Although 0.50 IU/mL is the most recommended cut-off value, some centers use the lower limit of normal (0.60 IU/mL). Secondly, the incidence of post-surgical bleeding, postpartum hemorrhage (PPH) and traumatic- or spontaneous bleeding after diagnosis of low VWF are still unknown. Lastly, it is hard to predict which individuals with low VWF have an increased bleeding risk. Therefore, we investigated the bleeding phenotype of individuals with historically lowest VWF levels of 0.31-0.50 IU/mL and 0.51-0.60 IU/mL, and the incidence of post-surgical bleeding, PPH and traumatic- and spontaneous bleeding after their initial diagnosis of "low VWF". Methods We performed a retrospective cohort study from January 2007 to November 2019 at the Erasmus MC, University Medical Center Rotterdam. All patients evaluated for the presence of a bleeding disorder with VWF antigen (VWF:Ag) and/or VWF activity (VWF:Act) and/or VWF collagen binding (VWF:CB) levels between 0.31-0.60 IU/mL, were included. Patients with VWF:Ag and/or VWF:Act and/or VWF:CB ≤0.30 IU/mL, acquired VWD and those with a concomitant bleeding disorder were excluded. For each individual we collected data from electronic patient files on baseline characteristics, reason for referral, family history of bleeding disorders, ISTH-BAT and laboratory measurements at diagnosis. Retrospective follow-up started from initial date of low VWF diagnosis through November 2019, during which we collected data on surgical procedures, pregnancies, and incidence of spontaneous- and traumatic bleeding. Results We included 439 patients; 269 patients with historically lowest VWF levels 0.31-0.50 IU/mL and 170 patients 0.51-0.60 IU/mL. Mean age at diagnosis was 28.8 ±17.7 years. Most patients were female (74.3%) and had blood group O (76.4%, Table 1). The bleeding score (BS) was similar in patients with historically lowest VWF levels of 0.31-0.50 IU/mL (3.7 ±3.0) and 0.51-0.60 IU/mL (4.0 ±2.9, p=0.209, Table 1). During the mean follow-up period of 6.3 ±3.7 years, 259 surgical procedures were performed in 146 patients, 81 deliveries in 56 women, and 109 spontaneous- or traumatic bleedings in 71 patients. The incidence of post-surgical bleeding was 7 (2.7%) during follow-up, whereas 8 deliveries (10%) were complicated by PPH. Overall, 65 out of 439 patients (14.8%) had a bleeding episode requiring treatment during follow-up, resulting in an incidence of bleeding requiring treatment of 0.5 ±1.9 per patient per decade. No difference was found in the incidence of bleeding requiring treatment between patients with historically lowest VWF levels of 0.31-0.50 IU/mL and 0.51-0.60 IU/mL (Figure 2A, p=0.154). We found that referral for a personal bleeding diathesis, a younger age at diagnosis and an abnormal BS at diagnosis were strong and independent risk factors for bleeding requiring treatment during follow-up, respectively HR=2.32 (95%CI: 1.16-4.63), HR=1.18 (95%CI: 1.01-1.38) and HR=1.77 (95%CI: 1.04-3.01). These risk factors were combined to develop a risk score to identify low VWF patients with an increased risk for bleeding requiring treatment (Figure 2B). The risk score performed excellent to differentiate in bleeding requiring treatment between low risk, intermediate risk and high risk patients (p<0.001, Figure 2C). The number of patients with bleeding requiring treatment was 8/126 (6.3%) in patients with low risk, 18/143 (12.6%) in intermediate risk and 39/170 (22.9%) in high risk patients (p<0.001). Likewise, the incidence of bleeding requiring treatment per patient per decade was 0.22 ±1.08 in low risk, 0.28 ±1.25 in intermediate risk and 0.87 ±2.61 in high risk patients (p=0.004, Figure 2D). Conclusion To conclude, there is no difference in the bleeding phenotype of individuals with historically lowest VWF levels of 0.31-0.50 IU/mL and 0.51-0.60 IU/mL. Therefore, the cut-off value to diagnose low VWF should be set at 0.60 IU/mL. Furthermore, the risk score developed in the current study may assist to identify low VWF patients with low, intermediate and high risk for future bleeding. Disclosures Atiq: SOBI: Other: travel grant; CSL Behring: Research Funding. Kruip:Boehringer Ingelheim: Research Funding; Pfizer: Research Funding; Bayer: Research Funding; Daiichi Sankyo: Research Funding; SOBI: Research Funding; Bayer: Speakers Bureau. Cnossen:Takeda: Research Funding; Shire: Research Funding; Baxter: Research Funding; Bayer: Research Funding; Sobi: Research Funding; CSL behring: Research Funding; Nordic Pharma: Research Funding; Novo Nordisk: Research Funding; Pfizer: Research Funding. Leebeek:CSL Behring: Research Funding; Shire/Takeda: Research Funding; Uniqure: Consultancy; Shire/Takeda: Consultancy; Novo Nordisk: Consultancy; SOBI: Other: Travel grant; Roche: Other: DSMB member for a study.

Download Full-text

P53 and CD34 Immunohistochemical Expression on Bone Marrow Biopsy As Predictive Marker of Response to Erythropoietin in Low Risk Myelodysplastic Syndrome

Blood ◽

10.1182/blood-2018-99-118811 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5511-5511

Author(s):

Gianluigi Reda ◽

Francesca Boggio ◽

Ramona Cassin ◽

Marta Riva ◽

Marco Barella ◽

...

Keyword(s):

Bone Marrow ◽

Myelodysplastic Syndrome ◽

Treatment Response ◽

Bone Marrow Biopsy ◽

Univariate Analysis ◽

Low Risk ◽

P Value ◽

P53 Expression ◽

Loss Of Response

Abstract Introduction: Erythropoietin stimulating agents (ESAs) are first-line therapy for International Prognostic Scoring System (IPSS)-low risk myelodysplastic syndrome (MDS) when symptomatic anaemia (Hb <10 g/dl) is associated with serum erythropoietin (EPO) <500 mU/mL. Treatment response rate, according to international working group (IWG) response criteria (1- 5), ranges from 40 to 60%. Attempts have been made to build prognostic scores (integrating transfusion need, erythropoietin level, R-IPSS and ferritin) able to predict response to ESAs (6-7). No data concerning the predictive value of morphological and immunohistochemical analysis on bone marrow biopsy in low risk MDS patients are emerged till now. Methods: We retrospectively examined 96 IPSS low/int-1 MDS patients treated with ESAs in order to evaluate the morphological and immunohistochemical features of the bone marrow biopsies performed at baseline. All the patients had hemoglobin (Hb) ≤10 g/dL and serum EPO <500 mU/mL and received EPO alfa or β 40 000-80 000 IU/week for at least 12 weeks. Response to ESAs treatment was evaluated according to IWG 2006 criteria. A detailed analysis of the morphological features (including quantitative and qualitative changes in the erythroid, myeloid and megakariopoyetic lineages) was performed, together with an immunohistochemical evaluation of p53 expression and CD34-positive blasts percentage. Results: Sixty-eight percent of the patients were classified as responder while 32% as non-responder. The morphologic profiles of the responder and non-responder did not differ significantly. A significant correlation was found between the response to the therapy and a percentage of CD34-positive blasts > 3% (univariate analysis: p= .0211). Moreover p53 expression in less than 1% of the nucleated cells correlated with the treatment response (univariate analysis: p = .0086). These results were also confirmed on multivariate analysis (p= .002). Fifty-eight percent of patients maintained response to ESAs for the entire duration of the follow up while 42% lost the response (median follow up: 35 months). More than 3% CD34-positive blasts was associated with a higher probability to lose the response to ESAs (p = .00003). Kaplan-Meier method was than applied to estimate the response duration. Patients with more than 3% CD34-positive blasts showed earlier loss of response in comparison with those with a lower percentage of blasts (p value= .0003; HR=3.9, IC 95% 1.8154-8.6238). Finally, the expression of p53 in more than ≥ 1% of the nucleated cells correlated with the loss of response before 24 mounts (p value= 0.029). Conclusions: Our study identifies 2 well-known parameters that could be useful to better predict outcome of ESAs therapy in low risk MDS patients. Therefore role of bone marrow biopsy together with its diagnostic contribution in the clinical evaluation of MDS patients (cellularity, morphologic dysplasia, percentage of CD34-positive blasts, grading of bone marrow fibrosis) could be helpful as a predictive tool in ESAs candidate patients. Further studies based on larger series of patients are needed to confirm these preliminary results. Disclosures Reda: Gilead: Consultancy; ABBVIE: Consultancy; Janssen and Cilag: Consultancy; Celgene: Consultancy. Riva:Jannsen and Cilag: Consultancy; Novartis: Consultancy; Celgene: Consultancy. Molteni:Janssen and Cilag: Consultancy; Novartis: Consultancy; Italfarmaco: Consultancy; Celgene: Consultancy; AMGEN: Consultancy. Cortelezzi:abbvie: Consultancy; novartis: Consultancy; roche: Consultancy; janssen: Consultancy.

Download Full-text

Low-Risk Polycythemia Vera Treated with Phlebotomies: Clinical Characteristics, Hematologic Control and Complications in 358 Patients from the Spanish Registry of Polycythemia Vera

Blood ◽

10.1182/blood-2021-145012 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3621-3621

Author(s):

Ana Triguero ◽

Alexandra Pedraza ◽

Manuel Pérez ◽

María Isabel Mata ◽

Beatriz Bellosillo ◽

...

Keyword(s):

Polycythemia Vera ◽

Research Funding ◽

Clinical Characteristics ◽

Treatment Strategies ◽

Myeloproliferative Disorders ◽

Primary Prophylaxis ◽

Low Risk ◽

Major Hemorrhage ◽

Risk Patients

Abstract Introduction: Current recommendations for patients with low-risk polycythemia vera (PV) include hematocrit (Htc) control with phlebotomies and primary prophylaxis of thrombosis with low-dose aspirin. There is scarce information regarding the hematological control, the incidence of complications and the need for cytoreduction in PV patients treated with phlebotomies only. Methods: A total of 358 patients with low-risk PV (<60 years old and without history of thrombosis) from the Spanish Registry of Polycythemia Vera were included in the present study. PV-related symptoms and blood counts were collected at 6, 12, 18, 24, 36, 48 and 60 months from diagnosis while the patients were treated with phlebotomies only. The duration of the treatment with phlebotomies, the indication of starting cytoreduction and the incidence of thromboembolic and hemorrhagic events during the cytoreduction-free period was also analyzed. Results: Baseline characteristics at the time of diagnosis are described in Table 1. Table 2 summarizes the main hematological and clinical characteristics under treatment with phlebotomies. Inadequate control of the Htc (> 45%) was reported in 61-70% of the patients, leukocytosis >15x10 9/l in 10% and thrombocytosis >1000x10 9/l in 5%. In addition, about 20% of the patients had pruritus and 10% had microvascular symptoms. Of the 358 patients included, 275 (77%) required cytoreduction, 261 (73%) with hydroxyurea and 14 (4%) with IFN. The main indication of cytoreduction was thrombocytosis (20%), followed by age >60 years old (15%) and microvascular symptoms (13%). Median duration of cytoreduction abstention was 4.7 (0.1-30.4) years being significantly longer in patients younger than 50 years (6 and 2 years for patients younger and older than 50 years, respectively, p<0.0001). With a follow-up of 1659 person-years under phlebotomy only treatment, 14 thrombosis were observed (arterial n=9, venous n= 5), 12 hemorrhages (major n=4, minor n=8) and 4 solid tumors (1 melanoma and 3 non-cutaneous carcinomas). The incidence of complications during the cytoreduction-free period by person-years was: 0.8% for thrombosis, 0.2% for major hemorrhage and 0.2% for second neoplasia. The median follow-up until last visit including the time after starting cytoreductive therapy was 8.4 (0.2-39) years. Of 14 deaths observed, none occurred during the phlebotomy period. Half of the patients died from PV related reasons but the other 50% were not related. The median survival estimation by K-M was 36.5 years. Disease progression was documented in 27 (7.5%) patients, 26 of them to myelofibrosis, 1 to myelodysplastic syndrome and none to acute leukemia. Progression to myelofibrosis occurred during the cytoreduction-free period in 5 patients (1.4%) after a median of 5.8 years (Range: 4.9-8.9). Conclusions The incidence of thrombotic and hemorrhagic complications was very low in this series of low-risk patients treated with phlebotomies, even though only 30-40% of patients maintained the Htc <45%. The data from the present study show that low-risk patients have different therapeutic needs than other PV patients and support the development of new treatment strategies. Representing the Spanish Group of Myeloproliferative Disorders. GEMFIN Figure 1 Figure 1. Disclosures Bellosillo: Qiagen: Consultancy, Speakers Bureau; Roche: Consultancy, Research Funding; Thermofisher Scientific: Consultancy, Speakers Bureau. Ferrer Marin: Cty: Research Funding; Incyte: Consultancy, Research Funding; Novartis: Speakers Bureau. Garcia Gutierrez: Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding.

Download Full-text

Incidence of PNH Clones by Diagnostic Code Utilizing High Sensitivity Flow Cytometry

Blood ◽

10.1182/blood.v118.21.1033.1033 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1033-1033 ◽

Cited By ~ 6

Author(s):

Mayur K Movalia ◽

Ilene c Weitz ◽

Seah H Lim ◽

Andrea Illingworth

Keyword(s):

Bone Marrow ◽

Hemolytic Anemia ◽

Research Funding ◽

Bone Marrow Failure ◽

High Sensitivity ◽

Diagnostic Code ◽

Follow Up Study ◽

Follow Up Studies ◽

Pnh Clone

Abstract Abstract 1033 Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic and life-threatening hematopoietic stem cell disorder characterized by deficiency of the GPI-anchored complement inhibitory proteins CD55/59. Chronic hemolysis from this deficiency leads to serious clinical morbidities including thromboembolism, chronic kidney disease, and increased mortality. The International Clinical Cytometry Society (ICCS) recommends multiparameter high sensitivity flow cytometry (HSFC) as the method of choice for diagnosing PNH. The ICCS also provides guidance on the clinical indications for testing for PNH, including patients (pts) with bone marrow failure (BMF), unexplained cytopenias, unexplained thrombosis, hemoglobinuria and hemolysis. The aim of this study is to use HSFC with sensitivity up to 0.01% to analyze 6,897 pts who were screened for PNH clones utilizing CD235a/CD59 for RBCs, FLAER/CD24/CD15/CD45 for neutrophils and FLAER/CD14/CD64/CD45 for monocytes. We evaluated the clinical indications for PNH testing with the provided ICD-9 diagnostic (DX) codes and examined the change in PNH clone sizes among pts who had follow-up studies in 3–12 months. Based on a sensitivity of at least 0.01%, 6.1% of all pts (421/6897) were found to be PNH positive. Of those pts, 5,545 pts (80.1%) had ICD-9 DX codes provided. The distribution of PNH clone sizes in these PNH+ pts is shown in Figure 1. Aplastic anemia (AA) and hemolytic anemia comprised the most common reasons for testing. In bone marrow failure syndromes, AA pts had the highest incidence of PNH+ clones, 26.3%, followed by pts with unexplained cytopenia, 5.7%, myelodysplastic syndrome (MDS), 5.5%, and anemia (unspecified or in chronic illness), 3.6% (Table 1). The incidence of PNH+ clones for symptoms such as hemolytic anemia was 22.7%, followed by hemoglobinuria 18.9%, and unspecified hemolysis, 7.9%, unspecified iron deficiency, 2.5%, and thrombosis, 1.4%. Of the 421 PNH positive pts, 89 pts (22%) were identified as having follow-up studies in 3–12 months. These pts were categorized into PNH clone sizes of 0.01% – 0.1% (27 pts, 30%), 0.11% – 1% (7 pts, 8%), 1.1% – 10% (18 pts, 20%) and 10.1% – 100% (37 pts, 42%). Of the 64 pts who had PNH clone sizes of 0.01% – 0.1% or 10.1 – 100%, one patient (0.02%) had a follow-up study that resulted in a change of category. Of the 25 pts with PNH clones sizes between 0.11% – 1% and 1.1% – 10%, 10 pts (40%) had a follow-up study resulting in an increase in category, 6 pts (24%) had a follow-up study resulting in a decrease in category and 9 pts (36%) had a follow-up study resulting in no change in category.Figure 1.Distribution of PNH Clone Sizes based on 421 PNH+ PatientsFigure 1. Distribution of PNH Clone Sizes based on 421 PNH+ PatientsTable 1:Incidence of PNH Clones in Patients with ICD-9 Diagnostic Code at Dahl-Chase Diagnostic ServicesICD-9 Diagnostic CodeGeneral DescriptionIncidence of PNH Clone284, 284.01, 284.8, 284.81, 284.89, 284.9Aplastic Anemia26.3% (94/357)238.7, 238.72, 238.73, 238.74, 238.75, 238.76Myelodysplastic Syndrome (MDS)5.5% (32/585)287.5Unexplained Cytopenia5.7% (13/230)284.1Pancytopenia6.0% (63/1058)285.2, 285.21, 285.29, 285.9Anemia Unspecified3.6% (40/1122)283, 283.1, 283.10, 283.11, 283.19, 283.2, 283.9Hemolytic Anemia22.7% (147/647)791, 791.2Hemoglobinuria18.9% (14/74)790.6, 790.99, 790.4Hemolysis7.9% (18/227)325, 415.1, 415.11, 434, 434.01, 444.22, 451.11, 451.19, 452, 453, 453.0, 453.2, 453.4, 453.41, 453.89, 453.9, 557, 557.1Thrombosis1.4% (14/967)280.9Unspecified Iron Deficiency2.5% (7/278)Other ICD-9 diagnostic codes2.1% (26/1232)Not Provided4.8% (51/1065)Note: Table reflects patients who had more than one ICD9 code associated with their laboratory tests. In this single-laboratory experience, we evaluated the incidence of PNH in these high risk groups. In this study, 26.3% of pts with the diagnosis of BMF had PNH+ clones detected, underscoring the need to test this group of pts. The study confirmed the utility of testing pts with unexplained hemolytic anemia, hemolysis and hemoglobinuria where the combined rate of positivity was 48%. In addition, this study highlights the need to monitor pts with small PNH clones by HSFC analysis as these pts may show significant variation over time. This examination of ICD-9 DX code association with presence of PNH+ clones confirms the need to actively test high risk populations for PNH based on the ICCS recommendations to ensure accurate diagnosis and early intervention. Disclosures: Weitz: Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Illingworth:Dahl-Chase: Employment; Alexion: Consultancy, Honoraria, Research Funding.

Download Full-text

Hemophagocytic Lymphohistiocytosis in Adults (aHLH): Results from the German HLH Registry

Blood ◽

10.1182/blood.v128.22.2523.2523 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2523-2523 ◽

Cited By ~ 4

Author(s):

Sebastian Birndt ◽

Thomas Schenk ◽

Frank M. Brunkhorst ◽

Georg Maschmeyer ◽

Frank Rothmann ◽

...

Keyword(s):

Diagnostic Criteria ◽

Hemophagocytic Lymphohistiocytosis ◽

Research Funding ◽

Cell Lymphoma ◽

Case Series ◽

B Cell Lymphoma ◽

Compound Heterozygous ◽

Cytokine Release ◽

Laboratory Findings

Abstract Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome caused by excessive immune activation leading to a life-threatening pro-inflammatory cytokine storm. HLH is not an entity of its own, but a clinical syndrome triggered by various conditions like infections, malignancy or autoimmune disorders. HLH pathogenesis is complex and still not fully understood. Contributing factors include immunosuppression (chemotherapy, long-term immunosuppressive therapy), cytokine release from tumor cells, imbalance between infected and immune effector cells as well as genetic predisposition. Despite improved HLH-specific therapy (adapted components from the pediatric HLH-1994 protocol), prognosis is still poor among adult HLH patients. Due to the lack of data on adult HLH in Germany, a national multicenter registry (http://www.hlh-registry.org/) was initiated. Methods: Patients (pts) with proven or suspected HLH were registered by 35 institutions across Germany from August 2010 to July 2016. Both HLH-2004 diagnostic criteria and the HScore (www.saintantoine.aphp.fr/score/) were used to confirm HLH diagnosis. To characterize adult HLH patients, data referring to underlying disease, treatment, outcome, clinical manifestations and laboratory findings were recorded. Where available, patient samples were tested for mutations of the perforin gene PRF1 by standard Sanger sequencing. Results: A total of 125 pts (48 female) were enrolled in our registry, of whom 105 pts either fulfilled diagnostic criteria according to HLH-2004 diagnostic guidelines (n=96) or met at least 4 out of 8 criteria and reached HLH-probability of over 90 % in the HScore (n=9). Among these 105 pts, n=38 (36 %) were female and n=67 (64 %) male. Median age at diagnosis was 49 years (range 17 - 81). Trigger diseases were in line with the literature, with infections (n=34) and malignancy (n=40) being most frequent (Table 1). Patients show a wide spectrum of underlying conditions, i.e. allogeneic stem cell transplantation (alloSCT) or HLH-mimicking diseases due to cytokine release in response to blinatumomab therapy. Late onset hereditary HLH was found in 3 pts (XLP-1 and -2 respectively in EBV-coinfected pts, one pt with perforin mutation - see below). 22 of 105 patients (21 %) were tested for PRF1 mutations. A compound heterozygous PRF1 A91V/Q405X mutation was identified in one pt presenting with NK/T-cell lymphoma. Heterozygous PRF1 A91V mutations were found in 2 pts with B-cell lymphoma and HLH following alloSCT respectively, in one case with available buccal swab DNA to prove germline origin of the mutation. Table 2 summarizes clinical and laboratory findings in the cohort. A median ferritin value of 32,000 µg/L underlines the importance to evaluate pts with highly elevated ferritin with respect to potential HLH diagnosis. Apart from fever and splenomegaly, clinical presentation frequently comprised hepatomegaly, liver failure, hyperbilirubinemia, renal failure, lung involvement like ARDS, or bleeding. Treatment included steroids in the vast majority of pts (n=89), often combined with i.v. immunoglobulins (n=47) and etoposide (n=49). After a median follow up time of 164 days, 48/97 pts (49.5 %) were alive, 8 pts were lost to follow up. Survival analysis revealed median overall survival of 454 days (Figure 1a). Comparing malignancy-associated HLH and HLH after alloSCT with infection- and autoimmune-associated HLH or HLH due to unknown triggers, survival was significantly poorer in the malignancy/alloSCT group (Figure 1b). Conclusions: HLH trigger conditions in adult patients in Germany are in accordance with published case series. Outcome in adult HLH is still poor, with malignancy-associated and HLH after alloSCT showing the worst prognosis. Diagnostic vigilance and early treatment is a prerequisite for improving outcome of adult HLH. In particular, high ferritin values should raise suspicion of HLH. Disclosures Hochhaus: Pfizer: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding; ARIAD: Honoraria, Research Funding.

Download Full-text

Clinical and Biological Characteristics and Outcomes of Richter Transformation : A French Multicenter Study from the Filo Group

Blood ◽

10.1182/blood-2019-128053 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4112-4112

Author(s):

Charline Moulin ◽

Romain Morizot ◽

Thomas Remen ◽

Hélène Augé ◽

Florian Bouclet ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Intermediate Risk ◽

Line Treatment ◽

First Line ◽

Advisory Committees ◽

Long Term Survivors ◽

First Line Treatment

Introduction: About 2 to 10% of patients (pts) diagnosed with Chronic Lymphocytic Leukemia (CLL) develop diffuse large B-cell lymphoma (DLBCL, so-called Richter transformation (RT)) over long-term follow-up. The outcomes of pts with RT are variable and poorly understood and there is no consensus on the best therapeutic approach. The aim of this study was to analyze the clinical characteristics, outcomes and factors predictive of survival in a large series of RT from the French Innovative Leukemia Organization (FILO). Methods: Biopsy-confirmed RT (limited to DLBCL and excluding Hodgkin lymphoma) diagnosed from 2001 to 2018 were identified from eight FILO centers. Clinical and biological characteristics of CLL and RT at diagnosis, including cytogenetics, clonal relation with the pre-existing CLL, Epstein-Barr virus (EBV) status, cell of origin (COO) analyzed by immunohistochemistry and RT score (Tsimberidou AM et al, J Clin Oncol, 2006) were analyzed as well as treatment and outcomes. Overall survivals (OS) were defined as time from CLL and RT diagnosis to death from any cause and analyzed using the Kaplan-Meier method. Statistical analyses were performed with SAS version 9.4. Results: A total of 70 CLL pts who developed RT were identified. The median age at CLL diagnosis was 62 years old (range 35-82), and 50 (71.4 %) were male. The median time to transformation was 5.5 years (range 0 to 22 years), with 12 simultaneous diagnosis of CLL and RT. Prior to RT, 20 (29%) pts had not been treated for CLL, 50 received one (n=21) or more (n= 29) line of treatment ; 6 pts had received a novel agent (ibrutinib, idelalisib or venetoclax). The median age at RT diagnosis was 68 years old (range 42-88). All biopsies were centrally reviewed; 38/58 pts (66%) had elevated LDH (>1.5N) ; 35/65 pts (54 %) had bulky disease (≥ 5 cm); 10/54 (18.5%) pts had del(17p) or TP53 mutation ; 9/42 pts (21%) had a complex karyotype (at least 3 abnormalities). The CLL and RT were clonally related in 27/27 (100%) tested pts. COO by Hans algorithm was non germinal center B cell-like (GCB) in 26/28 pts (93%). EBV was positive or detected in 5/40 (12.5%) pts. The median of Ki67 positivity was 70% (range 30% to 100%). The RT score (based at RT diagnosis on ECOG performance status 2-4, LDH >1.5 x normal, platelets<100 x 109/L, tumor size >5 cm and >1 prior therapy for CLL) was : low risk in 17 pts (31%), low-intermediate risk in 10 pts (19%), high-intermediate risk in 14 pts (25%) and high risk in 14 pts (25%). The most common first-line treatment of RT was immunochemotherapy (n=57, 87%) including R-CHOP-like regimen (n=48, 73%). Autologous or allogeneic transplantation was performed for 7 pts (11%). Response to first-line treatment was complete or partial response in 26 pts (40%), and stable disease or progression in 39 pts (60%). After a median follow-up of 8 years, 51/64 pts (80%) have died. The main causes of death were progressive DLBCL (n=36, 71%), infection (n=8, 16%) or progressive CLL (n=2, 4%). The median OS of the cohort from CLL and RT diagnosis (Figure 1) were 7.8 years and 9.5 months, respectively. In univariate analysis, patients with TP53 disruption at CLL stage, low platelets count, elevated LDH, elevated beta2-microglobulin, high ECOG score, high RT score, EBV positivity and absence of response to first-line RT treatment had worse OS. The ECOG score, platelets count and TP53 disruption remain significant in multivariate Cox-regression. Last, we compared the clinical and biological parameters of two Richter groups defined as: (i) short-term survivors (<12 months, n = 34) and (ii) long-term survivors (>48 months, n = 18). Long survival was significantly associated with elevated platelets count, low LDH, low ECOG, low RT score and response to RT first-line treatment. Discussion: The clinical outcomes of RT patients is poor and novel treatment options are needed. However, a group of long-term survivors was identified, characterized by elevated platelets count, low LDH, low ECOG, low RT score and response to immunochemotherapy. Disclosures Leblond: Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Thieblemont:Roche: Honoraria, Research Funding; Gilead: Honoraria; Novartis: Honoraria; Kyte: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Cellectis: Membership on an entity's Board of Directors or advisory committees. Cymbalista:Janssen: Honoraria; Gilead: Honoraria; AstraZeneca: Honoraria; Sunesis: Research Funding; Roche: Research Funding; Abbvie: Honoraria. Guièze:Abbvie: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Roche: Honoraria. Broseus:Janssen: Honoraria; Gilead: Honoraria; Novartis: Research Funding. Feugier:gilead: Honoraria, Research Funding, Speakers Bureau; janssen: Honoraria, Research Funding, Speakers Bureau; abbvie: Honoraria, Research Funding, Speakers Bureau; roche: Honoraria, Research Funding, Speakers Bureau.

Download Full-text