Non-AIDS-Defining Hematologic Malignancies in HIV-Infected Patients: A Nationwide Epidemiologic Study in Japan

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2183-2183
Author(s):  
Shotaro Hagiwara ◽  
Mihoko Yotsumoto ◽  
Seiji Okada
Keyword(s):  
Complete Remission ◽  
Hiv Infection ◽  
Highly Active Antiretroviral Therapy ◽  
Conflicts Of Interest ◽  
Hematologic Malignancy ◽  
Epidemiologic Study ◽  
Fold Increase ◽  
Hematologic Malignancies ◽  
The Mean ◽  
Hodgkin's Lymphomas

Abstract Abstract 2183 Background. The prevalence of HIV infection is estimated to be less than 0.1% in Japan; however, the number of newly reported HIV-infected persons has gradually increased, and the estimated number of HIV-infected patients now ranges from 6300 to 10000. Since the introduction of highly active antiretroviral therapy (HAART), the morbidity and incidence of AIDS-defining cancers has decreased. However, the incidence of non-AIDS-defining cancers has increased in Japan. To elucidate the incidence and clinical outcome of non-AIDS-defining hematologic malignancies, excluding non-Hodgkin's lymphomas, in HIV-infected patients, we conducted a nationwide epidemiologic study. Methods. We surveyed 429 regional AIDS centers and 497 educational hospitals certified by the Japanese Society of Hematology. Epidemiologic data for HIV was sourced from the Joint United Nations program on HIV/AIDS. Results. We obtained data from 511 institutes (55.4%). From 1991 to 2010, 47 cases of non-AIDS-defining hematologic malignancies were found—19 cases of Hodgkin's lymphoma (HD), 13 of AML, 7 of ALL, 4 of CML, 2 of multiple myeloma, 1 of CLL, and 1 of MDS-RAEB1. The mean age was 49.3 years (21–70 years), and 93.6% patients were male. The mean CD4-positive cell count was 303.7/μL (1–1371/μL). The mean duration from the diagnosis of HIV infection to hematologic malignancy was 45.0 months (0–204 months). Before diagnosis, 68.1% patients had been treated with HAART and 51.1% patients had AIDS. Sixteen of 19 HD patients were treated with ABVD or radiation therapy. Of these, 80% patients achieved complete remission, with a 2-year overall survival of 62.3%. Twelve of AML and 6 of ALL patients were treated with standard induction chemotherapy. Eight of twelve patients (66.7%) with AML and five of six patients (83.3%) achieved complete remission. The median survival for both AML and ALL patients was 16 months, with 42.8% ALL and 30.8% AML patients alive after 4 years. Comparison of the last 2 decades (1991–2000 and 2001–2010) showed a 4.7-fold increase in the incidence of hematologic malignancies (11.5 vs. 54.6/100000 person-years). Conclusion. A nationwide epidemiologic study revealed that HIV-infected patients are at high risk of hematologic malignancies, and that the incidence of hematologic malignancies has increased in the past decade. The prognosis was equivalent to that of HIV-negative patients, and standard chemotherapy may be a feasible treatment option for HIV-infected patients with hematologic malignancies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Hematological Profile of HIV-Infected Patients on First-Line Highly Active Antiretroviral Therapy and Its Correlation With CD4 Count

2021 ◽  
Author(s):  
John Jospeh Diamond Princy ◽  
Kshetrimayum Birendra Singh ◽  
Ningthoujam Biplab ◽  
Ningthoukhongjam Reema ◽  
Rajesh Boini ◽  
...  
Keyword(s):  
Platelet Count ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Highly Active Antiretroviral Therapy ◽  
Cd4 Count ◽  
Total Leukocyte Count ◽  
Hiv Patients ◽  
Positive Correlation ◽  
Highly Active ◽  
The Mean

Abstract Introduction Human immunodeficiency virus (HIV) infection is a state of profound immunodeficiency. Disorders of hematopoietic system are a common but often overlooked complication of HIV infection. This can manifest at any stage of the disease but more commonly in the advanced stage with low CD4 count. Anemia is the most common hematological abnormality in HIV patients and prevalence ranges from 1.3 to 95%. As HIV disease progresses, the prevalence and severity of anemia also increase. Hence, this study was undertaken to assess the hematological parameters of HIV-infected patients on highly active antiretroviral therapy (HAART) at different treatment durations with the hope to improve the HAART outcome in HIV patients and its correlation with CD4 count. Methods This prospective longitudinal study enrolled 134 HIV-infected patients admitted to or attending the OPD in the Department of Medicine or Antiretroviral Therapy (ART) Center (Center of Excellence), Regional Institute of Medical Sciences (RIMS), Imphal, Manipur, from 2018 to 2020. Complete hemogram, CD4 count, and other related-blood investigations were studied. Results The mean age of the study population was 39.9 ± 11.04 years. Of the 134 patients, 75 (56%) were males and 59 (44%) were females. Twelve (9%) patients had a history of injecting drug use (IDU). TLE (tenofovir, lamivudine, efavirenz) regimen was started on 112 (83.6%) patients and the majority of them (69/134 [51.5%]) had a CD4 count of 200 to 499 cells/mm3, which increased significantly 6 months after HAART to 99 to 1,149 cells/mm3, with a mean of 445 ± 217 cells/mm3. There were significant improvements in hemoglobin (Hb) levels, total leukocyte count (TLC), absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) after HAART indicating a positive correlation with CD4 count (p < 0.05). Thrombocytopenia was observed higher after HAART when compared to baseline. There was a positive correlation between platelet count and CD4 count. However, the mean corpuscular volume (MCV) and erythrocyte sedimentation rate (ESR) had a negative correlation with CD4 count. Conclusion The study inferred a strong positive correlation between CD4 and Hb levels, TLC, ANC, ALC, and platelet count after HAART with improvement in these values as CD4 count increases. Specific treatment intervention based on the changes in the immunohematological profile trends can help prevent most of the adverse effects on HIV patients in our community.

scholarly journals Pharmacokinetics and Safety of a 7-Day Administration of Intravenous Itraconazole followed by a 14-Day Administration of Itraconazole Oral Solution in Patients with Hematologic Malignancy

2001 ◽  
Vol 45 (3) ◽  
pp. 981-985 ◽  
Author(s):  
Marc A. Boogaerts ◽  
Johan Maertens ◽  
Ronald Van Der Geest ◽  
Andre Bosly ◽  
Jean-Louis Michaux ◽  
...  
Keyword(s):  
Steady State ◽  
Hematologic Malignancy ◽  
Oral Treatment ◽  
Hematologic Malignancies ◽  
Oral Solution ◽  
Once Daily ◽  
Intravenous Treatment ◽  
Good Safety Profile ◽  
The Mean ◽  
Trough Plasma

ABSTRACT The pharmacokinetics and safety of an intravenous hydroxypropyl-β-cyclodextrin solution of itraconazole administered for 7 days followed by itraconazole oral solution administered at 200 mg once or twice daily for 14 days were assessed in 17 patients with hematologic malignancies. Steady-state plasma itraconazole concentrations were reached by 48 h after the start of intravenous treatment. The mean trough plasma itraconazole concentration at the end of the intravenous treatment was 0.54 ± 0.20 μg/ml. This concentration was not maintained during once-daily oral treatment but increased further in the twice-daily treatment group, with a trough itraconazole concentration of 1.12 ± 0.73 μg/ml at the end of oral treatment. As expected in the patient population studied, all patients experienced some adverse events (mainly gastrointestinal). Biochemical and hematologic abnormalities were frequent, but no consistent changes occurred. In conclusion, 7 days of intravenous treatment followed by 14 days of twice-daily oral treatment with itraconazole solution enables plasma itraconazole concentrations of at least 0.5 μg/ml to be reached rapidly and to be maintained. The regimen is well tolerated and has a good safety profile.

scholarly journals Venous Thromboembolism Following L-Asparaginase Treatment in Hematologic Malignancies in Korea

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4679-4679
Author(s):  
Ji Hyun Lee ◽  
Ho-Young Yhim ◽  
Soo-Mee Bang
Keyword(s):  
Health Insurance ◽  
Venous Thromboembolism ◽  
Conflicts Of Interest ◽  
Splenic Vein ◽  
Epidemiologic Study ◽  
Hematologic Malignancies ◽  
Population Based ◽  
Assessment System ◽  
Insurance System ◽  
Asian Patients

Abstract Background: L-asparaginase (L-asp) is one of the important drugs to make the change of cure higher in acute lymphocytic leukemia (ALL) and some lymphomas. The risk of thrombosis in ALL patients after L-asp use is known to be 2.4-5.4% in pediatric and 5.9-34% in adult. Although the prevalence of venous thromboembolism (VTE) in Asian is generally lower compared with Western populations, there are few reports about the incidence of VTE in Asian patients with hematologic malignancies treated with L-asp. In this study we performed a nationwide population-based epidemiologic study to provide basic information regarding the incidence rate and risk factors of VTE in Korean patients with hematologic malignancies after L-asp treatment. Methods: Using the Korean Health Insurance Review and Assessment Service (HIRA) database, patients treated with L-asp from 2009 to 2013 were retrospectively identified by medication codes. The National Health Insurance (NHI) is the only public medical insurance system operated by the Ministry for Health, Welfare and Family Affairs in Korea. The NHI program of Korea covers the whole population as a compulsory social insurance system. Therefore, there are no exceptions for seasonal, part-time or unemployed workers. HIRA is a government-affiliated organization to build an accurate claims review and quality assessment system for the NHI. According to data from the Korean Statistical Information Service (http://kosis.kr/) the Korean population was 48 580 293 in 2010. Also, according to data from the NHI, the registered populations was 50 581 000 in 2010. There is a difference in population figures between data from the Korean National Statistical Office and the NHI because of overseas Koreans. A population-based study was possible for this study because the NHI basically covers all Korean residents and also the population itself is ethnically homogeneous. The HIRA database includes both hospitalization cases and outpatient clinic cases. All cases were included in the study when there was evidence of L-asp treatment. Among the cases with L-asp, VTE cases which has occurred after L-asp treatment were identified when the starting date of the VTE diagnostic codes was between the start date of L-asp and 3 months after the end of L-asp treatment. Results: During the year 2009 to 2013, a total of 3304 patients were prescribed with colaspase in any type of hematologic malignancies including ALL and lymphoma. Patients who were treated with pegarspase or crisantaspase were not included. Among the 3304 patients, 118 patients (3.57%) had occurred VTE. The most common site of thrombosis was upper extremities (44/118 = 37.29%) followed by deep vein (30/118 = 25.42%) and pulmonary artery (30/118 = 25.42%), inferior vena cava (6/118 = 5.08%), portal vein (3/118 = 2.54%), cerebral sinus (2/118 = 1.69%), renal vein (2/118 = 1.69%), and splenic vein (1/118 = 0.85%). Among the 1809 patients 18 years or younger, 37 patients (2.05%), and among the 1501 patients 19 years of older, 81 patients (5.39%) suffered from VTE (P < 0.0001). Other factors including gender, disease (ALL or lymphoma), type of steroids (prednisone or dexamethasone) and use of anthracyclines did not appear to be associated with VTE after L-asp treatment. Conclusions: This is the largest epidemiologic study in Asian patients with hematologic malignancies with L-asp treatment. The incidence of thrombosis after L-asp use was comparable with Western populations, and the risk was higher in adults compared with pediatrics. Concomitant use of prednisone and anthracyclines did not affect VTE occurrence. Disclosures No relevant conflicts of interest to declare.

Tolerability of Pegylated Liposomal Doxorubicin 20 mg/m2 Every 2 Weeks in the Management of Kaposi’s Sarcoma and Hematologic Malignancies.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3897-3897
Author(s):  
David H. Henry ◽  
Susan Kilcoyne ◽  
Jonathan N. Latham ◽  
Arthur P. Staddon
Keyword(s):  
Initial Dose ◽  
Highly Active Antiretroviral Therapy ◽  
Kaposi's Sarcoma ◽  
Liposomal Doxorubicin ◽  
Hematologic Malignancy ◽  
Pegylated Liposomal Doxorubicin ◽  
Dose Intensity ◽  
Kaposi’S Sarcoma ◽  
Hematologic Malignancies ◽  
Lymphocytic Leukemia

Abstract Pegylated liposomal doxorubicin (PLD, Doxil) was developed to decrease the risk of cumulative-dose cardiotoxicity associated with conventional doxorubicin. However, hand-foot syndrome (HFS) and stomatitis were associated with PLD in early clinical trials and were more common when patients with ovarian cancer received 50 mg/m2 q4w (HFS, 37.4%; stomatitis, 37.4%) than when patients with AIDS-related Kaposi’s sarcoma (KS) received 20 mg/m2 q3w (HFS, 3.4%; stomatitis, 6.8%). PLD is now commonly used with a dose intensity of 10 mg/m2 per week (20 mg/m2 q2w, 30 mg/m2 q3w, or 40 mg/m2 q4w). Recent reports with this reduced dose intensity have shown a marked decrease in the rate and grade of HFS and stomatitis. This retrospective chart review was performed to examine the tolerability and effectiveness of PLD 20 mg/m2 q2w in patients with KS and hematologic malignancies. Patient charts from a community oncology clinic from January 2000 through December 2004 were reviewed. Data abstracted included patient demographics, PLD dosing, treatment response, and tolerability for all PLD recipients. Data were censored for patients with solid tumors or an initial PLD dose other than 20 mg/m2 q2w. Of the 157 patients receiving PLD, 65 received 1206 cycles (range, 1–116; median, 17) of PLD at an initial dose of 20 mg/m2 every 2 weeks as a component of care for KS (n=55), multiple myeloma (n=4), non-Hodgkin’s lymphoma (NHL, n=4), Hodgkin’s disease (n=1), or chronic lymphocytic leukemia (n=1). Most patients with KS also received highly active antiretroviral therapy (HAART). No signs (eg, decreased ejection fraction) or treatment-related symptoms (eg, shortness of breath) of cardiotoxicity were reported in any patient. Four patients (6.2%) had documented mild HFS; 3 patients with KS and 1 patient with a hematologic malignancy One case of HFS (1.5%) led to discontinuation of PLD. Three patients (4.6%) had documented symptoms of mucositis; all 3 patients had KS (5.5%). PLD was effective in most patients at this dose intensity; clinical response (complete or partial response) was seen in 55 patients (84.6%), stable disease in 1 patient (1.5%), and progression in 3 patients (4.6%, all with NHL), and response could not be determined in 5 patients (7.7%). The results of this retrospective review suggest that PLD at an initial dose of 20 mg/m2 q2w is active and well tolerated, and that HFS and stomatitis occur in a low percentage of patients and rarely result in discontinuation. Moreover, the rates of HFS seen in patients with KS and hematologic malignancies seem similar. Prospective studies in larger populations are required to confirm the efficacy and safety of PLD 20 mg/m2 q2w as a component of care for hematologic malignancies. Incidences of Targeted Adverse Events During Treatment with PLD 20 mg/m2 KS (n = 55) Hematologic Malignancies (n = 10) Cardiotoxicity 0 (0.0%) 0 (0.0%) Mucositis 3 (5.5%) 0 (0.0%) HFS 3 (5.5%) 1 (10.0%)

Low Prevalence of Asymptomatic Neutropenia in Thailand.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1411-1411
Author(s):  
Panisinee Lawasut ◽  
Thanyaphong Na Nakorn ◽  
Ponlapat Rojnuckarin ◽  
Tanin Intragumtornchai
Keyword(s):  
Neutrophil Count ◽  
Urban Areas ◽  
Mexican American ◽  
Conflicts Of Interest ◽  
Smoking Status ◽  
Epidemiologic Study ◽  
Related Factors ◽  
Thai Population ◽  
The Mean ◽  
Low Prevalence

Abstract Abstract 1411 Poster Board I-434 Background: The prevalence and etiology of asymptomatic neutropenia in Asians are still unknown. Therefore, we conducted the epidemiologic study to survey the frequency and related factors of neutropenia in general Thai population. Method: Blood samples from healthy Thai citizens resided in Bangkok and 4 provinces from different areas were collected from October 2008-May 2009. Absolute neutrophil count (ANC) < 1.50 ×109/l was used as the cut-off point for neutropenia.[1] Results: Six thousand nine hundred and seventy one samples were analyzed. There were 2,422 male and 4,549 female. The median age was 49 years (range 15-93 years). The subjects from Bangkok (n=4,297) are younger and are more commonly male compared to those from non-urban areas (n=2,674) (p<0.01). The overall mean white blood cell count (WBC) and ANC were 7.57±4.07 ×109/l (mean ± 2SD) and 4.18 ±3.05 ×109/l (mean ± 2SD), respectively. The prevalence of neutropenic cases were 0.43% (30 cases, 95%CI 0.41-0.44). The mean percentage of the circulating neutrophil count was 54.58±17.25% (mean ± 2SD). It was notable that 1.87% of the participants had the circulating WBC ≥ 12.6 ×109/l. There was no influence of age, sex or survey sites on the prevalence of neutropenia. The neutropenia subjects defined as ANC lower than 2SD of the studied populations (1.13 ×109/l) were only 8 cases (0.11%). The prevalence of cases, which ANC < 1.0 and 0.5 ×109/l, were 0.03% and 0% respectively. Conclusion: The frequency of asymptomatic neutropenia in Thai was 0.43% defined by ANC < 1.50 ×109/l. Compared with the previous largest population report[1], the prevalence were lower than that of American white (0.79%, 95%CI 0.57-1.01), African American (4.47%95%CI 3.92-5.02) and similar to Mexican American (0.38%, 95%CI 0.24-0.52). The underlying cause of these racial discrepancies remains to be explored. [1] Hsieh MM, Everhart JE, Byrd-Holt DD, Tisdale JF, Rodgers GP. Prevalence of neutropenia in the U.S. population: age, sex, smoking status, and ethnic differences. Ann Intern Med. 2007 Apr 3;146(7):486-92. Disclosures: No relevant conflicts of interest to declare.

Management Of PICC-Associated Thrombosis In Patients Receiving Chemotherapy For Hematologic Malignancies

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5000-5000
Author(s):  
Meera Sridharan ◽  
Aref Al-Kali ◽  
Aneel A. Ashrani ◽  
Kebede Begna ◽  
Michelle Elliott ◽  
...  
Keyword(s):  
Platelet Count ◽  
Conflicts Of Interest ◽  
Hematologic Malignancy ◽  
Superior Vena ◽  
Vena Cava ◽  
Hematologic Malignancies ◽  
Limited Information ◽  
Jugular Veins ◽  
Increased Risk

Abstract Background Tunneled central venous catheters have traditionally been used for administration of chemotherapy (chemo) for acute leukemia treatment. Peripherally inserted central catheters (PICC) are increasingly being used, but there is an increased risk of PICC-associated thrombosis (PAT). There is limited information on management of PAT in this subgroup of patients (pt). Methods In this retrospective cohort study we investigated the primary management of PICC related upper extremity venous thrombosis (TB) in pt with hematologic malignancy undergoing chemo at Mayo Clinic Rochester.  Eligible pt were 18 years and older, had documentation of PICC placement at our institution, initiation of chemo within a week of PICC placement, and the TB was objectively documented by compression venous ultrasound (CVU).   Superficial venous TB (SVT) was defined as TB of subcutaneous veins (basilic and cephalic) and deep venous TB (DVT) defined as TB of brachial, axillary, subclavian, or innominate superior vena cava and internal jugular veins. We retrospectively stratified initial management (IM) into 1) PICC removal alone (PR), 2) PR and therapeutic anticoagulation (AC), 3) AC alone, and 4) conservative management (CM) consisting of symptomatic care and observation.  We also investigated factors influencing IM of PAT.  Long term outcomes including incidence of pulmonary embolism (PE), post phlebitic syndrome and recurrence of TB were noted. Results Between 2006 and 2012, 190 pt with AML (n=160), MDS or MDS/MF (n=10), or ALL (n=20) met our study criteria.  Overall, 40/190 (21.6%) developed PAT: AML n=38, ALL n=1, MDS/MF n=1. SVT occurred in 16/40 (40%) pt and DVT occurred in 24/40 (60%) pt. IM is shown in Table 1. One pt with SVT received AC for 6 weeks as well as PR.  In this pt, IM included AC because of proximity of TB to deep veins. 7 pt had a follow up (f/u) CVU within 3 months demonstrating: TB progression (prog, n=1, IM with PR alone but with prog AC was started); TB stability (stab, n=2, both IM with PR alone) and TB resolution/improvement (R/I, n= 4, 2 IM with PR and 2 IM with CM)  In the 5 pt with CM, 2 pt had f/u CVU demonstrating improvement, one pt had charted clinical improvement , and 2 pt had no charted clinical f/u. Of DVT pt on AC (n=14), 5 pt completed at least 2 months of AC.  Reasons for early cessation (n=9) of AC included thrombocytopenia (tcp, n=4), hematoma (n=1), hematuria (n=1), subarachnoid hemorrhage (n=1), and unknown (n=1).   One pt died 2 days after presence of DVT was noted. Two pt initially treated with PR alone developed a second TB with placement of a new PICC on contralateral arm and AC was subsequently initiated (duration: 3 months (n=1), and 8 days (n=1)). 14 pt with DVT had f/u CVU within 3 months which demonstrated prog (n=2), stab (n= 8), or R/I ( n=4) of TB (Table 2). The 2 pt with TB prog subsequently received longer term AC guided by platelet count.   In 5 pt with PICC not initially removed, 3 pt had PR after completion of chemo. (1-4 days), one pt had PR at discharge (27 days from TB), and one pt had PICC in place on discharge. One pt with DVT experienced a PE within one year f/u.  This pt had initially completed 3 days of AC which was stopped because of tcp. Conclusion In this cohort of patients with PAT, the most common IM consisted of PR, which appeared to result in a low recurrence rate among pt with SVT.  In pt with DVT, the role of AC remains to be defined given the abbreviated course of AC in most pt.  Though, the lack of CVU followup in all pt limits conclusions, there appeared to be a low rate of symptomatic prog.  Initiation of AC was largely guided by platelet count and degree of occlusive symptoms. Thrombocytopenia was also the most commonly cited reason for discontinuing AC.  Close clinical follow up aided by the use of CVU was integral to ensure that PAT did not lead to further adverse events. Disclosures: No relevant conflicts of interest to declare.

Effectiveness of Darbepoetin alfa Administered Every 3 Weeks on Clinical Outcomes in Patients with Hematologic Malignancies and Chemotherapy-Induced Anemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3767-3767 ◽  
Author(s):  
Ralph Vincent Boccia ◽  
Peter T. Silberstein ◽  
Simon Tchekmedyian ◽  
Dianne Tomita ◽  
Greg Rossi ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Darbepoetin Alfa ◽  
Hematologic Malignancy ◽  
Hematologic Malignancies ◽  
Target Range ◽  
Tumor Type ◽  
Open Label ◽  
Serious Adverse Events ◽  
The Mean ◽  
Tumor Types

Abstract Patients (pts) with cancer receiving chemotherapy commonly have chemotherapy-induced anemia (CIA), often resulting in reduced quality of life. The primary objective of this analysis was to summarize the effectiveness of darbepoetin alfa (DA) administered at 300mcg every 3 weeks (Q3W), in achieving and maintaining a hemoglobin (Hb) target range of 11–13g/dL in pts with hematologic malignancies and CIA, versus pts with solid tumors and CIA. Data for all 1493 pts enrolled in this multicenter, open-label, 16-week study who received at least one dose of DA are included in this exploratory analysis stratified by tumor type. Pts ≥18 years of age receiving multicycle chemotherapy and with Hb &lt;11g/dL were eligible for this study. Hb-based endpoints were adjusted for red blood cell transfusions and analyzed with and without imputing missing Hb values. Pt-reported outcomes were assessed using the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) scale. Most pts were white (79%), 61% were female, and the median age was 64 years (range, 19 to 97). At baseline (BL), 31% of pts had Hb &lt;10g/dL and 61% had Hb ≥10g/dL; the mean (SD) was 10.1 (0.7)g/dL. Hematologic malignancy (14%) was the third most common tumor type after breast (29%) and gastrointestinal (24%); 45% of the hematologic malignancies were non-Hodgkin’s lymphoma (NHL) pts. Hb, transfusion, and FACT-F endpoints are shown in the table. A slightly lower percent of NHL pts achieved the Hb target range recommended by current guidelines (11–13g/dL), compared to pts with other hematologic malignancies or with solid tumors. Similar proportions of pts with hematologic malignancies or solid tumors maintained Hb within the target range. The proportion of pts receiving RBC transfusions from week 5 to the end of study (EOS) was similar for pts with hematologic malignancies and for pts with solid tumors. Improvements in FACT-F scores were seen in all groups, although the mean change was lower in NHL pts compared with other tumor types. Serious adverse events were as expected for this patient population. DA Q3W appears to be effective in achieving and maintaining Hb between 11 to 13g/dL in pts with CIA and hematologic malignancies. Since chemotherapy is often administered Q3W, synchronizing DA treatment with pts’ chemotherapy schedules may simplify the treatment of CIA in these pts. Hematologic - NHL N=98 Hematologic - non-NHL N=118 Solid N=1277 All Tumor Types N=1493 *For pts who achieved target. **For pts available at day 29. K-M=Kaplan Meier. CL=confidence limits Mean (95%CL) BL Hb (g/dL) 10.1 (9.9, 10.2) 10.0 (9.8, 10.1) 10.1 (10.1, 10.2) 10.1 (10.1, 10.2) Pts who achieved ≥ Hb 11g/dL. Crude % (95% CL) 74 (66, 83) 82 (75, 89) 79 (77, 81) 79 (77, 81) Proportion of pts maintaining Hb between 11 and 13g/dL after achieving target - n (%)* 51 (70) 68 (70) 739 (73) 858 (73) Time to target Hb (weeks). K-M Median (95% CL) 7 (6, 8) 6 (4, 7) 4 (4, 5) 4 (4, 5) Transfusions from week 5 to EOS. Crude % (95% CL)** 21 (13, 30) 20 (13, 27) 18 (16, 20) 18 (16, 20) Mean change in FACT-F from BL to week 16 (95% CL) 2.8 (−0.9, 6.5) 5.2 (1.8, 8.6) 4.8 (3.9, 5.7) 4.7 (3.9, 5.6)

Vitamins, Minerals, and Specialty Supplements and Risk of Hematological Malignancies In the VITamins and Lifestyle (VITAL) Cohort Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4143-4143
Author(s):  
Filippo Milano ◽  
Roland B. Walter ◽  
Theodore M. Brasky ◽  
Emily White
Keyword(s):  
Folic Acid ◽  
Dietary Supplements ◽  
Hematological Malignancies ◽  
Conflicts Of Interest ◽  
Hematologic Malignancy ◽  
Hematologic Malignancies ◽  
Cox Proportional Hazards ◽  
Case Control Studies ◽  
History Of ◽  
Incident Cases

Abstract Abstract 4143 Introduction: The use of vitamins and dietary supplements is a common health practice in many parts of the world, in part because of the belief that they will prevent diseases, including cancer. However, results of epidemiologic studies regarding their efficacy in reducing the risk of any cancer, particularly hematologic malignancies, are inconsistent and are mostly limited to case-control studies. Materials: Participants were male and female members of the VITamins And Lifestyle (VITAL) cohort. Between 2000 and 2002, 64,839 men and women, aged 50 to 76 years, who lived in the region of Washington State covered by the Surveillance, Epidemiology, and End Results (SEER) registry, were recruited. Participants were excluded if they had any cancer prior to baseline other than non-melanoma skin cancer and were censored at the time of diagnosis of a non-hematologic malignancy during follow-up; after exclusions, there were 64,839 participants available for study. Incident cases of hematologic malignancies were identified through December 2008 by linkage to the SEER registry. Participants answered questions on the frequency (days/week), duration (years), and dose per day of their supplemental use of vitamins, including A, B3, B6, B12, C, D, E, multivitamin compounds, and folic acid; minerals, including calcium, selenium, iron, magnesium, chrome, and zinc during the 10 years before baseline. For the non-vitamin, non-mineral “specialty” supplements, garlic, ginseng, and fish oil, only frequency and duration were ascertained. Use of vitamin and mineral supplements was categorized into non-users and tertiles of use, such that the highest category was greater than could be achieved only by use of a common multivitamin (Centrum Silver). 10-year average use of specialty supplements was categorized into: non-user; low use, <4 days/week or <3 years; and high use, ≥4 days/week and ≥3 years. Multivariable-adjusted Cox proportional hazards models were used to estimate hazards ratios (HR) and 95% confidence intervals (95% CI) of the use of dietary supplements with the risk of total hematologic malignancies. Models were adjusted for age, sex, race/ethnicity (white/hispanic/other), education, smoking, self-rated health, physical activity, history of anemia in the year before baseline, and family history of leukemia or lymphoma. Results: A total of 577 case of hematological malignancies were identified including MDS [n=54], AML [n=36], myeloproliferative disorders [n=46], CLL/SLL [n=88] and other non-Hodgkin lymphomas [n=235], Hodgkin lymphomas [n=22], plasma cell disorders [n=66], mature NK/T cell neoplasms [n=17], and other entities [n=13]). None of the vitamin 10-year average intakes were associated with decreased risk of incident hematologic malignancies There was no evidence that high use of vitamins A (HR=0.79, 95% CI: 0.58–1.08; p-trend=0.28), B12 (HR=0.98, 95%CI: 0.73–1.31; p-trend=0.26), C (HR=0.97, 95% CI: 0.77–1.22; p-trend=0.99), D (HR=0.90, 95% CI: 0.62–1.31; p-trend=0.45), or folic acid (HR=1.00, 95% CI: 0.73–1.39; p-trend=0.19) was associated with the risk of blood cancer. Among specialty supplements, only high 10-year average use of garlic was significantly associated with a reduced risk of development of blood cancers (HR=0.64,95% CI: 0.42–0.98); however the association was not linear (p-trend=0.14). Conclusions: We observed no reduction in the risk of incident hematologic malignancies with dietary supplement and vitamin use with the exception of garlic when used at a high amount (≥4 days/week for ≥ 3 years). Disclosures: No relevant conflicts of interest to declare.

Nonmyeloablative conditioning followed by transplantation of genetically modified HLA-matched peripheral blood progenitor cells for hematologic malignancies in patients with acquired immunodeficiency syndrome

Blood ◽  
2002 ◽  
Vol 99 (2) ◽  
pp. 698-701 ◽  
Author(s):  
Elizabeth M. Kang ◽  
Moniek de Witte ◽  
Harry Malech ◽  
Richard A. Morgan ◽  
Sheila Phang ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Highly Active Antiretroviral Therapy ◽  
Genetically Modified ◽  
Allogeneic Transplantation ◽  
Hematologic Malignancies ◽  
Myelogenous Leukemia ◽  
Hodgkin Disease ◽  
Highly Active ◽  
Acute Myelogenous ◽  
Immunodeficiency Syndrome

Abstract To assess the safety and efficacy of nonmyeloablative allogeneic transplantation in patients with HIV infection, a clinical protocol was initiated in patients with refractory hematologic malignancies and concomitant HIV infection. The results from the first 2 patients are reported. The indications for transplantation were treatment-related acute myelogenous leukemia and primary refractory Hodgkin disease in patients 1 and 2, respectively. Only patient 1 received genetically modified cells. Both patients tolerated the procedure well with minimal toxicity, and complete remissions were achieved in both patients, but patient 2 died of relapsed Hodgkin disease 12 months after transplantation. Patient 1 continues in complete remission with undetectable HIV levels and rising CD4 counts, and with both the therapeutic and control gene transfer vectors remaining detectable at low levels more than 2 years after transplantation. These results suggest that nonmyeloablative allogeneic transplantation in the context of highly active antiretroviral therapy is feasible in patients with treatment-sensitive HIV infection.

scholarly journals Germline POT1 Variants Can Predispose to a Variety of Hematologic Neoplasms

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 2-4
Author(s):  
Tristan L. Lim ◽  
David B. Lieberman ◽  
Adam R. Davis ◽  
Ryan Hausler ◽  
Ashkan Bigdeli ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Hematologic Malignancy ◽  
Hematologic Malignancies ◽  
Molecular Testing ◽  
Hematologic Neoplasms ◽  
Lymphoid Malignancies ◽  
Myeloid Neoplasms ◽  
Common Diagnosis ◽  
Cancer Syndromes

Germline mutations in the shelterin component protection of telomeres 1 (POT1) were recently found to be associated with familial chronic lymphocytic leukemia (CLL), melanoma, glioma, and several other familial cancer syndromes. The role of POT1 mutations in myeloid neoplasms and other hematologic malignancies, however, remains unknown. To explore the role of POT1 variants in hematologic neoplasms, we analyzed POT1 variants in 3323 consecutive patients who underwent next-generation sequencing (NGS) of a panel of hematologic malignancy-associated genes at our institution and characterized the clinical and pathological characteristics of patients with germline and somatic POT1 mutations. Of 3323 consecutive patients who underwent NGS, 2770 patients had a hematologic malignancy (lymphoid n = 1299, myeloid n = 934, and both lymphoid and myeloid n = 537), while 553 patients were evaluated for non-malignant cytopenias. All 57 patients (2.06%) carrying either a POT1 disease-associated variant or variant of uncertain significance had a hematologic malignancy compared to no identified POT1 variants in 553 patients with benign cytopenias (OR = 23.5, p &lt; 0.001), suggesting that the presence of POT1 variants was predictive of a hematologic malignancy. Of 57 patients, 33 had lymphoid malignancies, 23 had myeloid neoplasms, and 2 had a lymphoid and myeloid neoplasm (Fig 1). Patient variants were classified as germline or somatic using constitutional DNA sequencing, POT1 emergence/disappearance over time, or POT1 maintenance in remission. In the absence of these data, likely germline or likely somatic designations were made by assessing variant allele frequencies against clinical/pathologic characteristics. 18 patients (33%) were found to have germline or likely germline POT1 variants (29% and 42% in the lymphoid and myeloid malignancy groups, respectively). Another 6 patients (11%) had variants whose germline status could not be determined. Of the 17 unique germline POT1 variants, 10 were missense and located within mapped functional protein domains, while 7 were classified as predicted loss-of-function (pLOF) due to a disruption of start, premature stop, frameshift, or spice site alteration. Patients with hematological malignancies had a ~5-8x increased odds of having a germline pLOF POT1 variant compared to cancer-free individuals in the Genome Aggregation Database (gnomAD, n = 113,108 exomes, OR = 7.5, p &lt; 0.001) or in the Penn Medicine BioBank (PMBB, n = 7877, OR = 5.0, p = 0.010), with a prevalence of 0.25% compared to 0.03% and 0.05%, respectively. Germline pLOF POT1 variants were significantly more enriched in patients with myeloid (gnomAD: OR = 6.1, p = 0.02) and lymphoid (gnomAD: OR = 9.8, p &lt; 0.001; PMBB: OR = 6.5, p = 0.004) malignancies. In 33 patients with lymphoid malignancies and POT1 variants, the most common diagnoses were CLL/SLL (n = 21, germline n = 6, somatic n = 12), CD5- CD10- indolent B cell neoplasms (n = 4, germline n = 1, somatic n = 3), and multiple myeloma (n = 3, all somatic) (Table 1). Lymphoid malignancies with a germline POT1 variant had a relative paucity of additional mutations; in contrast, somatic POT1 variants frequently co-occurred with other mutations, most commonly with TP53 (Fig 2, n = 5, 23%). Among 23 patients with myeloid malignancies, patients with germline POT1 variants developed malignancies at a significantly younger age compared to those whose POT1 variants were somatic (median age 59.5 vs 70.5 years, p = 0.04). The most common diagnosis in patients with myeloid neoplasms carrying germline POT1 variants was MPN (germline n = 5, somatic n = 1). AML, MDS/MPN, and MDS occurred in 4, 3, and 1 patients respectively. All patients with myeloid neoplasms had additional disease-associated mutations, with the most common co-occurring variants in TET2 (n = 7), JAK2 (n = 6, co-occurring with 50% of germline POT1 myeloid variants), and NRAS (n = 6). In conclusion, this is the first comprehensive analysis of POT1 variants in an unselected hospital-based population undergoing molecular testing for variants associated with hematologic malignancies. Our results show that the presence of POT1 variants is predictive of having a hematologic neoplasm and that over 30% of POT1 variants in hematologic malignancy patients are germline. Our study expands the spectrum of POT1-associated familial neoplasms and highlights the needs for better recognition of familial hematologic cancer syndromes. Disclosures No relevant conflicts of interest to declare.

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