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  • 1
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 3159-3159
    Abstract: Background Atypical HUS (aHUS) is a rare thrombotic microangiopathy (TMA) caused by complement dysregulation. Eculizumab is a humanized monoclonal antibody targeting against complement factor C5. Ravulizumab, a longer acting C5 inhibitor developed through minimal, targeted modifications to eculizumab was recently approved for treatment of aHUS in 2019. Here we describe the clinical presentation, laboratory, genetic profile, treatment along with long-term sequelae of patients diagnosed with aHUS. The outcomes of restrictive use of eculizumab and the use of ravulizumab were also studied. Materials and Methods We conducted a single center retrospective cohort study, searching electronic medical records of patients diagnosed and treated for aHUS at University of Arkansas for Medical Sciences, from January 1, 2013 to January 31, 2021, after IRB approval. Inclusion criteria :1) Presence of microangiopathic hemolytic anemia (MAHA) with thrombocytopenia 2) ADAMTS13 activity & gt; 10 % 3) Age & gt; 18. Exclusion criteria: 1) Age & lt; 18 years 2) TMA associated with hemolytic uremic syndrome, scleroderma renal crises, anti-phospholipid syndrome. Results Seventeen patients meeting the inclusion criteria were enrolled in the study. The mean age at diagnosis was 47.4 ± 17.9 years. Most of the patients were Caucasians (n=10, 58%) and females (n= 14, 82%). All the patients except one had acute kidney injury (AKI) at presentation (n=16, 94.1%), the most frequent extra-renal presentation was CNS involvement -seizures, confusion and altered mental status (n= 7, 41.2 %) followed by Gastrointestinal- non-bloody diarrhea, nausea and vomiting (n=5, 29.4 %) [Figure 1]. Lab investigations are described in [Table 1] . Complement genetic testing was done in 100% of study population. Factor H related genes 1/3 (CFHR1/3) and complement factor H (CFH) were the most commonly found pathogenic mutations [Table 2]. In this study, pregnancy and infection (n= 4, 23.5% each) were identified as the most common triggers [Figure 2] . For two of the patients, it was the first pregnancy and for the other two, it was their second and third pregnancies. They presented at the second, sixth, and sixteenth week postpartum respectively. Eleven (64.70%) patients developed chronic kidney disease (CKD) with six (35.29%) patients progressing to end stage renal disease (ESRD). Two (11.76 %) pregnant patients developed cardiomyopathy, two (11.76%) patients developed pulmonary complications (pneumonia and pulmonary hypertension) and three (17.64%) patients developed epilepsy. All the postpartum females in our study were able to breastfeed while on eculizumab with no long-term complications in the neonates. One patient had two subsequent deliveries with no ante, intra, or post-partum consequences or repeated triggers of aHUS. Fourteen patients (82.3%) received therapeutic plasma exchange, four (23.5%) patients received iv methyl prednisone (1mg/kg) and two (11.7%) patients received IVIg prior to initiating eculizumab. Over time, five (29.41%) patients opted to completely stop drug therapy and four patients (23.52%) chose to shift to ravulizumab because of the ease of treatment duration (every 8 weeks rather than every 2 weeks for eculizumab). All these nine patients remained in remission with stable hematologic and renal parameters on subsequent follow-ups [Table 3]. Three patients (17.6 % mortality) died in our study due to causes unrelated to aHUS. Conclusions: The clinical diagnosis of atypical HUS can be challenging especially with extra-renal manifestations. Females were four times more affected than males. PCMs were present in 11 patients. Early diagnosis and treatment with C5 inhibitors improves morbidity and mortality. The decision to discontinue or switch eculizumab to ravulizumab will likely decrease healthcare costs and improve patient compliance but should be based on disease severity. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
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    ISSN: 0006-4971 , 1528-0020
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    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 2
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    American Society of Hematology ; 2022
    In:  Blood Vol. 140, No. Supplement 1 ( 2022-11-15), p. 3698-3699
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 3698-3699
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
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  • 3
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    American Society of Hematology ; 2021
    In:  Blood Vol. 138, No. Supplement 1 ( 2021-11-05), p. 1629-1629
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 1629-1629
    Abstract: BACKGROUND Heavy chain diseases (HCDs) are B-cell neoplasms characterised by production of monoclonal (M) protein consisting only of immunoglobulin heavy chain without a bound light chain. Three types have been recognized- IgA alpha HCD (most common, a form of extra nodal marginal zone lymphoma of mucosal associated lymphoid tissue aka immunoproliferative small intestinal disease [IPSID], Mediterranean lymphoma or Seligmann disease] , IgG gamma HCD (aka Franklin's disease, variant of lymphoplasmacytic lymphoma) and IgM mu HCD (rarest, resembles chronic lymphocytic leukemia). Limited data is available regarding the epidemiology, survival patterns, and incidence of second primary malignancies in patients with HCD in the Unites States. MATERIALS AND METHODS We performed a retrospective analysis using SEER* stat version 8.3.9 statistical software and November 2020 submission of SEER 18 registry which covers ~ 27.8 % of US population based on the 2010 census. We identified all cases & gt; 1 years old diagnosed with Heavy chain disease between 2000 and 2018 using International Classification of Diseases for Oncology edition 3 (ICD-O-3) code 9762/3. We analyzed survival using Kaplan- Meier method, and MP-SIR session was used to calculate the risk of second primary malignancy. RESULTS A total of 64 cases of HCD were identified. Most common primary sites of involvement were bone marrow (82.8%), lymph nodes (9.3%), GI tract (3.1%), others (4.6%)- spleen, blood and vertebral column. The crude, age-adjusted to 2000 US standard population and age-specific incidence rate of HCD in the United States is & lt; 1/100,000 respectively. The median age at diagnosis is 68 years with incidence in males being about 1.3 times that of females. Bimodal age distribution was observed, with peak incidence between ages 60-64 and 75-79 [Figure 1]. In our entire cohort, 82.8% (n=53) patients were Caucasians, 15.6 % (n=10) patients were African Americans, and 1.5% (n=1) patients were American Indian/Alaska Native. Among Caucasians, 56.6% (n=30) patients were males, and 43.3% (n=23) patients were females. Between 2000-2018, the maximum cases (n=7 each) were diagnosed in the year 2002 and 2008 [Figure 2] The median overall survival for the entire cohort was 48 months (95% CI: 35- 61). Overall survival rates of all ages, sex and race at 1 year, 2 year and 5 years were found to be 86.1%, 71.4%, 57.8% respectively. OS at 5 years declines after 70 years .Patients with HCD are at risk of developing subsequent solid and haematological malignancies within 5 years of diagnosis. 9 (14 %) cases developed SPMs: urinary bladder (n=1), lung and bronchus (n=2), Hodgkin-nodal (n=1), Non-Hodgkin Lymphoma -extra nodal (n=1), GI cancers [stomach (n=1), esophagus (n=1) and ascending colon (n=1)], miscellaneous (n=1). [Figure 4] . The mean follow-up duration for new SPM was 51 months. Overall, 39 patients died: 3 (4%) from miscellaneous malignant cancer and 11 (17%) patients from haematological malignancy; the most common being Non-Hodgkin lymphoma (n=8), followed by Hodgkin lymphoma (n=1), Multiple myeloma (n=1) and leukemia (n=1). CONCLUSIONS HCD is an extremely rare haematological malignancy. The incidence of HCD is proportionately higher among Caucasians as compared to other races, with no reported case among Asian or Pacific Islanders. Among Caucasians, males and females have approximately equal risk of acquiring HCD. Most patient die because of their primary haematological malignancy. We recommend close follow-up for at least the first 5 years after initial diagnosis. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 4
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    American Society of Hematology ; 2019
    In:  Blood Vol. 134, No. Supplement_1 ( 2019-11-13), p. 2404-2404
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 2404-2404
    Abstract: Introduction Disseminated Intravascular Coagulation (DIC) is a systemic coagulopathy which leads to widespread thrombosis and hemorrhage and ultimately results in multiorgan dysfunction. DIC usually occurs as a complication of illnesses like severe sepsis, malignancies, trauma, acute pancreatitis, burns, and obstetrical complications. The prognosis and mortality of DIC depend on the etiology, however, the mortality of DIC is known to be on the higher side. The aim of the study is to analyze if gender, race, regional differences have any association with the mortality of hospitalized patients with DIC. Method The National Inpatient Sample database from the Healthcare Cost and Utilization Project (HCUP) for the year 2016 was queried for data. We identified hospital admissions for DIC with the International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis code D65. The data was analyzed with STATA 16.0 version and univariate and multivariate analysis were performed. We studied the characteristics of all such hospitalizations for the year 2016 and the factors associated with the in-hospital mortality rate (MR) of DIC. We used length of stay, cost of stay as an outcome to determine if gender, race, and location play a role in the mortality. Results A total of 8704 admissions were identified with a diagnosis of DIC during the year 2016. The mean age for admission was found to be 56.48± 0.22. The percentage of admissions in females and males did not have a notable difference (50.57% vs 49.43%). The disease specific MR for DIC was 47.7%. Admission during weekend vs weekdays did not carry a statistically significant difference in terms of MR. Females with DIC were less likely to die in the hospital when compared to males with DIC (OR= 0.906, CI 0.82 - 0.99, p= 0.031). Interestingly, African Americans (AA) with DIC admissions were found to have 24% more risk of dying when compared to Caucasians admitted with DIC (OR= 1.24, CI 1.10 - 1.39, P= 0.00), Native Americans (NA) has 67% more risk of dying when compared to Caucasians (OR= 1.67, CI 1.03 - 2.69, p= 0.035). The mortality rate of NA, AA, Caucasians with DIC was found to be 57%, 52%, 47% respectively. The MR was found to be highest in hospitals of the northeast region (52%), then hospitals in the south (47%), followed by west and mid-west (46%), p= 0.000. Patients admitted to west and mid-west were 24% less likely to die when compared to patients admitted to northeast region hospitals (OR= 0.76, p= 0.001). The average length of stay and cost of stay were also less in west and mid-west regions when compared to north east. The difference in outcomes persisted after adjusting for age, gender, race, hospital division, co-morbid conditions. Conclusion Our study demonstrated that African Americans and Native Americans with DIC have high risk of dying in the hospital. Also, there exists a difference between the mortality rate, length and cost of stay among different regions in the United States. More research is needed to elucidate the factors that might be impacting the location-based variation in mortality. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 5
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    American Society of Hematology ; 2019
    In:  Blood Vol. 134, No. Supplement_1 ( 2019-11-13), p. 4857-4857
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 4857-4857
    Abstract: Introduction The overall impact of morbidity related to sickle cell disease (SCD) is enormous due to decreased quality of life, high health care utilization and immense financial strain on the patients and health care system. Patients with SCD have also been found have high hospital readmission rates compared to other medical conditions, further leading to increased health care burden. The objective of this study was to explore the common reasons, healthcare utilization and identify modifiable factors associated with 30-day readmission in patients with SCD using the most recently available national data in the United States. Methods Cohort selection. 2016 Nationwide Readmission Database (NRD) from the Healthcare Cost and Utilization Project (HCUP) by the Agency for Healthcare Research and Quality (AHRQ) was queried for analysis. NRD captures discharge data from 22 states, representing about 50% of all hospitalizations in the United States. National estimates can be produced by using sampling weights provided by the NRD. Patients with SCD were identified by using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis code D57. Patients younger than 18 years were excluded. Readmission was defined as any admission within 30 days of index hospitalization discharge. Statistical Analysis. Sampling weights were used throughout all calculations, facilitating appropriate national projections. Percentages in all figures reflect national estimates. Chi-square test and Student's t-test were used for univariate analysis. Multivariable logistic regression analysis was done to determine independent predictors of 30-day readmission in patients with SCD. Data analyses was performed using SAS v9.4 (SAS Institute, Cary, NC). Results In a total of 83,692 hospitalizations for SCD in 2016, 15,880 (18.9%) had at least one 30-day readmission and 40% of the readmissions occurred within the first two weeks of discharge. The most common reason for 30-day readmission was due to complications of SCD (29.8%) with sickle-cell pain crisis (18.4%) being the most frequent one. The other common causes for readmission were sepsis (10.3%), cardiac related (9.7%), respiratory failure (6.2%), renal failure (4.3%) and mood related (4.04%). Female sex (P 〈 0.001), younger age (p 〈 0.01) and patients with public insurance (P 〈 .001) were more likely to be readmitted. Multivariable logistic regression analysis showed age 31-45 years (OR 1.28, 95% CI 1.16 - 1.40, P 〈 0.01), alcohol abuse (OR 1.39, 95% CI 1.17 - 1.66, P 〈 0.001), opioid abuse (OR 2.66, 95% CI 2.34 - 3.02, P 〈 0.0001), depression (OR: 1.59, 95% CI 1.45 - 1.73, P 〈 0.01), substance abuse (OR: 1.35, 95% CI 1.21 -1.50, P 〈 0.001), tobacco use (OR: 1.35, 95% CI 1.24 - 1.46, P 〈 0.01), heart failure (OR: 1.81, 95% CI 1.66 - 1.97, P 〈 0.002), COPD (OR: 1.74, 95% CI 1.55 - 1.96, P 〈 0.03) were significantly associated with 30-day readmission while adjusting other co-morbidities. The mean cost of readmission was an additional $39,259 (±182). Conclusion This study showed that the 30-day readmission rate in patients with SCD in 2016 has decreased to less than 20% compared to previously published rates (31.9%, Elixhauser A, 2013). While this decrease in readmission rate is encouraging, further studies are needed to investigate the reasons for this trend. Several modifiable risk factors were identified in this study such as alcohol, tobacco, opioid, substance abuse and depression which can be addressed to potentially bring down the readmission rate further and improve patient care. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 6
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    Online Resource
    American Society of Hematology ; 2020
    In:  Blood Vol. 136, No. Supplement 1 ( 2020-11-5), p. 36-37
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 36-37
    Abstract: Introduction Peripheral T-cell lymphoma (PTCL) is diverse group of an uncommon and aggressive type of non-Hodgkin lymphoma (NHL). It generally affects people aged 60 years and above and is diagnosed slightly more often in men than in women. However, younger adults and children are also diagnosed with PTCL. Being a rare entity, the best treatment regimen has not been established for newly diagnosed patients or for relapsed/refractory patients with PTCL. In general, treatment outcomes have been poor with conventional chemotherapy regimens. Methods We performed a retrospective cohort study of patients with newly diagnosed and relapsed PTCL, and its subtypes, who are seen in the hematology-oncology clinic at the University of Arkansas for Medical Sciences from July 2014 to December 2019. The demographics of the study population, the frontline and second-line treatment strategies for all the subtypes and the response to the treatment were studied. Also, the role of high dose chemotherapy followed by autologous stem cell transplantation (HDT-ASCT) in the overall survival (OS) and progression-free survival (PFS) is analyzed. Results Out of the 48 patients, 45.8% (n=22) patients had PTCL not otherwise specified (PTCL NOS) type, 29% (n=14) had Anaplastic large cell lymphoma ALK-negative subtype, 4.2 % (n=2) had Anaplastic large cell lymphoma ALK-positive subtype, Angioimmunoblastic T-cell lymphoma, Extra nodal NK/T cell lymphoma, Enteropathy associated T- cell lymphoma each. The mean age of diagnosis was 58 ± 2. Males were affected more when compared to females (66.6% vs 33.3%). Also, Caucasians were more affected than African Americans (73% vs 25%). The mortality of PTCL was found to be 40%. After frontline treatment, complete response (CR) was observed in 43.7% (n= 21) patients, partial response (PR) was observed in 18.7% (n= 9) patients, stable disease (SD) was seen in 4% (n=2), progression of disease (PD) was observed in 12.5% (n= 6) patients. Stem cell transplant (HDT-ASCT) was done for 28% (n=13) of patients who achieved CR after frontline chemotherapy (CR1). Relapse was observed in 60% of patients. Patients with stage III and IV on the initial diagnosis had a higher chance of relapse or refractory disease. After the second-line treatment, out of 20 patients, 9 patients had CR, 5 had PR, 5 patients had PD, 1 patient had SD. CR was observed in 7 patients with either brentuximab vedotin alone or brentuximab vedotin with combination chemotherapy as second-line treatment. The OS and PFS were found to be higher in patients who received HDT-ASCT after CR1. Conclusion PTCL has a high risk of relapse and there are no uniform guidelines for the treatment of PTCL in relapsed or refractory setting. The currently available second line treatment options have shown modest response rates. Our study has shown that brentuximab vedotin, when used alone or in combination, showed better response rate in the relapsed setting. Also, stem cell transplant improved the overall survival and progression-free survival in patients with PTCL after frontline chemotherapy. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
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  • 7
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    American Society of Hematology ; 2019
    In:  Blood Vol. 134, No. Supplement_1 ( 2019-11-13), p. 4848-4848
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 4848-4848
    Abstract: Introduction Sickle cell disease (SCD) associated pain is a significant health care issue in the United States which prompts physicians to prescribe opioids to help treat and prevent the recurrent acute painful episodes. Despite nationwide efforts to reduce narcotic pain medication usage, opioids still remain as the mainstay of pain management in SCD. Many SCD patients are using marijuana to help with their pain, anxiety, appetite, mood and sleep as per recent studies. Cannabinoids in marijuana interact with the body's endocannabinoid system which has receptors in almost every major bodily system. The effect of cannabinoids on these receptors reduces the signaling of inflammatory responses and also reduce cytokine production. Very few states have approved SCD as a qualifying condition for medical marijuana. But we are still unsure about the medical benefits of marijuana in SCD patients as there are very limited studies done so far. In our study, we sought to examine the characteristics and complications of marijuana usage in sickle cell patients. Methods The National Inpatient Sample database for the year 2016 was used to identify admissions with a primary diagnosis of SCD and we grouped patients into those who have a diagnosis of cannabis related disorders (CRD) and those who do not have the diagnosis. ICD- 10 codes are used for identifying the SCD patients and also for CRD. Statistical analysis was performed using STATA and univariate and multivariate analysis were performed. The outcomes that are studied included mortality, length and cost of stay, hospital regions and the association of marijuana use with anxiety, mood disorders. We also studied the association of marijuana with the complications of SCD such as sickle cell pain crisis, vaso occlusive crisis, acute chest syndrome, splenic sequestration, avascular necrosis. Results A total of 37,307 admissions with a principal diagnosis of SCD were identified, out of which 4.09% (N= 1526) had cannabis use disorders. The median age of patients with CRD was found to be 31.21 ± 0.3 when compared to 30.67 ± 0.09 in patients without CRD. Even though SCD admissions were more commonly seen in females when compared to males (61.78% vs 38.22%), cannabis use was seen more associated with males (57.97% vs 42.03%). The in-hospital mortality of SCD was less (0.56%) as compared to the mortality rates of other hematological malignancies. The association of cannabis use with in-hospital mortality was found to be not statistically significant. Also, the median length of stay was less in patients with CRD when compared to patients without CRD (4.88 ± 0.2 vs 5.11 ± 0.03) and also likewise cost of stay. Based on the hospital regions in the US, Cannabis use in SCD was seen more prevalent in South region (44%), then Midwest or north-central (26%), northeast (19%), west (10%) and the result was statistically significant (p= 0.003). The association of cannabis use was not found to be statistically significant with acute chest syndrome and splenic sequestration. Cannabis use was, however, found to be associated with the vaso occlusive crisis and avascular necrosis (OR=1.02, p=0.003 and OR= 1.14, 0.022 respectively) even though we cannot say that cannabis use could be a risk factor as there are other confounding factors like coagulopathy, chronic debilitating conditions. Interestingly, SCD patients with CRD have more risk of developing anxiety (OR= 2.32, p=0.000) and also mood disorders (OR= 2.5, p= 0.001) when compared to SCD patients without CRD. The difference persisted after adjusting for age, gender, race, co-morbidities. Conclusion Marijuana use is more seen in the southern and north-central regions in patients with SCD. Marijuana use was not found to be associated with in-hospital mortality in sickle cell patients. SCD patients are using marijuana mainly for alleviating their pain and sometimes for its euphoria effect. Our study showed that it can cause anxiety and mood disorders. The main limitation of our study was the moderate sample size for SCD patients with CRD. The impact and interaction between CRD and SCD complications need to be evaluated separately in a larger study to get accurate values. Large randomized control trials have to be done to assess if SCD qualifies for prescription of medical marijuana as it possesses benefits as well as risks. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 8
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 5658-5659
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
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  • 9
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 13216-13217
    Type of Medium: Online Resource
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    Publisher: American Society of Hematology
    Publication Date: 2022
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  • 10
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 5172-5173
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Publisher: American Society of Hematology
    Publication Date: 2022
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