Pure Red Blood Cell Aplasia and Chronic Lymphocytic Leukemia

Abstract Introduction/Objective Leukostasis/symptomatic hyperleukocytosis is commonly seen in acute leukemias and is characterized by high blast counts and symptoms of decreased tissue perfusion with a one-week mortality of 20-40%, if left untreated. It is a rare complication in chronic lymphocytic leukemia (CLL) and is seen in CLL patients with white blood cell (WBC) counts > 500x10^9/L. Studies have shown that transfusion of blood products prior to decreasing the WBC count may lead to increased blood viscosity and worsen leukostasis. We report a CLL patient with a lower WBC count presenting with symptoms of leukostasis, further worsened by a red blood cell (RBC) transfusion prior to leukapheresis. Methods/Case Report A 73-year-old male with history of CLL for 5 years, hypertension and chronic kidney disease presented with acute dyspnea for 1 day. The WBC count was 208x10^9/L, hemoglobin was 6.5 g/dL, troponin I was 1.554 ng/mL, creatinine was 1.68 mg/dL and chest x-ray showed bilateral interstitial lung edema. The patient was diagnosed with acute hypoxic respiratory failure, acute kidney injury and myocardial infarction due to leukostasis. He received RBC transfusion, shortly after which his dyspnea worsened. There were no other signs or symptoms that could suggest a transfusion reaction. A single leukapheresis was performed following which there was a significant improvement in symptoms with a drop in WBC count to 123.1x10^9/L and creatinine to 1.3 mg/dL. Results (if a Case Study enter NA) NA Conclusion CLL may present with symptomatic hyperleukocytosis at lower leukocyte counts than has been described in the literature. Symptoms due to leukostasis can be precipitated/worsened by transfusion of blood products due to increased blood viscosity. It is critical to identify the signs and symptoms of this medical emergency as prompt diagnosis and management with leukapheresis significantly reduces the leukocyte count and blood products should be transfused slowly during or after leukapheresis.

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Pseudohyperkalemia in Patients with Chronic Lymphocytic Leukemia

International Journal of Nephrology ◽

10.4061/2011/759749 ◽

2011 ◽

Vol 2011 ◽

pp. 1-3 ◽

Cited By ~ 9

Author(s):

Stephen I. Rifkin

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Blood Cell ◽

Mechanical Stress ◽

White Blood Cell ◽

Whole Blood ◽

Correct Diagnosis ◽

Plasma Potassium ◽

Lymphocytic Leukemia ◽

Blood Potassium

Pseudohyperkalemia occurs occasionally in patients with extreme leukocytosis. Increased white blood cell fragility coupled with mechanical stress is felt to be causal. Serum and plasma potassium levels have been both associated with pseudohyperkalemia. Whole blood potassium determination will usually verify the correct diagnosis. It is important to diagnose this condition early so that patients are not inappropriately treated. Two patients with chronic lymphocytic leukemia and extreme leukocytosis are presented, one with pseudohyperkalemia and one with probable pseudohyperkalemia, and diagnostic considerations are discussed

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Epoetin Alfa vs Standard of Care Decreases Number of Packed Red Blood Cell Transfusions in Patients Receiving Hyper-CVAD for Acute Lymphocytic Leukemia, Lymphoblastic Lymphoma, and Burkitt’s Lymphoma.

Blood ◽

10.1182/blood.v108.11.4477.4477 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4477-4477

Author(s):

Maria E. Cabanillas ◽

Deborah A. Thomas ◽

Hagop Kantarjian ◽

Gloria N. Mattiuzzi ◽

Benjamin N. Bekele ◽

...

Keyword(s):

Blood Cell ◽

Red Blood Cell ◽

Acute Lymphocytic Leukemia ◽

Standard Of Care ◽

Burkitt’S Lymphoma ◽

Lymphoblastic Lymphoma ◽

Lymphocytic Leukemia ◽

Burkitt's Lymphoma ◽

Epoetin Alfa ◽

Red Blood Cell Transfusions

Abstract Background: Anemia is common in patients with acute lymphocytic leukemia (ALL), lymphoblastic lymphoma (LL), and Burkitt’s lymphoma (BL) treated with chemotherapy and is associated with poor cancer control. Studies have shown that even mild correction of anemia has been associated with a significant improvement in quality of life. Although there are studies that show a survival benefit in patients receiving epoetin alfa (EPO), there are at least two randomized trials which reported negative outcomes with respect to progression-free survival in patients with solid tumors treated with EPO. The current standard of care for treatment of anemia in ALL, LL, and BL is packed red blood cell transfusions (PRBC). However, transfusions are time consuming and carry risks of infection and transfusion reaction. Objectives: To evaluate if EPO 1) decreases number and frequency of transfusions, and 2) adversely influences the complete remission (CR) rate to chemotherapy. Methods: Patients with newly diagnosed ALL, LL, or BL receiving hyper-CVAD were randomized to EPO vs standard of care within 14 days of starting chemotherapy. EPO dose was 40,000 units SQ weekly and escalated to 60,000 units after four weeks if indicated. Both arms received blood transfusions as per uniform guidelines. Patients were considered evaluable if they had been on the study for at least five weeks. Results: Forty-six of 70 patients were evaluable and included in this first interim analysis; 23 were treated with EPO. There were 16 ALL, 4 BL, and 3 LL on EPO and 20 ALL, 1 BL, and 2 LL in the standard of care arm. The two groups were comparable in baseline hemoglobin and number of courses of chemotherapy completed. Median age was lower in the EPO arm (32, range 20–71) when compared to the standard of care arm (42, range 16–68; p=0.37). There were more male patients in the EPO arm than standard of care arm (14 vs. 9; p= 0.144). Median baseline erythropoietin level was 299 (range 12–10532) in the EPO arm vs. 104 (range 7–491; p=0.02) in the standard of care arm. The median total number of PRBC units in the EPO group was 12 (range 4–23) compared with 16 (range 9–31) in the standard of care group (p= 0.01). The median number of transfusion events (frequency) was 7 (range 2–13) in the EPO arm compared with 9 (range 4–18) in the standard of care arm (p= 0.03). Time to neutrophil and platelet recovery was comparable in both arms. All patients with ALL had a CR in both arms. On the EPO arm, 1 patient with BL and 1 patient with LL had a partial remission. One patient with LL on the EPO arm had no response to chemotherapy. All patients with BL and LL on the standard of care arm had a CR (p=0.073). Conclusions: In patients with ALL, LL, and BL on hyper-CVAD, EPO decreased the frequency and number of packed red blood cell transfusions. EPO does not affect recovery of other cell lines. Use of EPO in this patient population does not appear to have an adverse impact on CR rates in patients with ALL. The numbers of BL and LL are too small to draw conclusions regarding effect of EPO on response rates.

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Epoetin-alpha compared to standard of care decreases number of packed red blood cell transfusions in patients receiving hyper-CVAD for acute lymphocytic leukemia, lymphoblastic lymphoma, and Burkitt’s lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.7075 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 7075-7075

Author(s):

M. E. Cabanillas ◽

D. A. Thomas ◽

H. Kantarjian ◽

G. N. Mattiuzzi ◽

B. N. Bekele ◽

...

Keyword(s):

Blood Cell ◽

Red Blood Cell ◽

Acute Lymphocytic Leukemia ◽

Standard Of Care ◽

Burkitt’S Lymphoma ◽

Lymphoblastic Lymphoma ◽

Lymphocytic Leukemia ◽

Burkitt's Lymphoma ◽

Platelet Recovery ◽

Response To Chemotherapy

7075 Background: Anemia is common in patients with acute lymphocytic leukemia (ALL), lymphoblastic lymphoma (LL), and Burkitt’s lymphoma (BL) treated with chemotherapy and is associated with poor cancer control. Studies have shown that mild correction of anemia is associated with a significant improvement in quality of life. The current standard of care (SOC) for treatment of anemia in ALL, LL, BL is packed red blood cell (PRBC) transfusions. Objectives: To evaluate if EPO 1)decreases number/frequency of transfusions, and 2) adversely influences the complete remission (CR) rate. Methods: Patients with newly diagnosed ALL, LL, or BL receiving hyper-CVAD were randomized to EPO vs SOC within 14 days of starting chemotherapy. EPO dose was 40,000 units SQ weekly and escalated to 60,000 units after 4 weeks if indicated. Both arms received PRBC transfusions as per guidelines. Patients were considered evaluable if they had been on the study for at least 5 weeks. Results: 46 of 70 patients were evaluable: 16 ALL, 4 BL, and 3 LL on EPO (total 23) and 20 ALL, 1 BL, 2 LL in the SOC arm (total 23). The 2 groups were comparable in baseline hemoglobin and number of courses of chemotherapy completed. Median baseline erythroepoietin level was 299 (r 12–10,532) in the EPO arm vs. 104 (r 7–491; p=0.02) in the SOC arm. Time to neutrophil and platelet recovery was comparable in both arms. All patients with ALL (both arms) achieved a CR. One patient with LL on the EPO arm had no response to chemotherapy while all patients with BL and LL on the SOC arm achieved a CR. Conclusions: 1) EPO significantly decreased the frequency and number of PRBC transfusions in patients with ALL, LL, and BL on hyper-CVAD. 2) EPO does not affect recovery of other cell lines. 3) Use of EPO does not appear to have an adverse impact on CR rates in patients with ALL. No significant financial relationships to disclose. [Table: see text]

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The Development of Marked Elevation in White Blood Cell Count Does Not Predict Inferior Outcome in Chronic Lymphocytic Leukemia

Leukemia & Lymphoma ◽

10.1080/10428190290026295 ◽

2002 ◽

Vol 43 (6) ◽

pp. 1245-1251 ◽

Cited By ~ 1

Author(s):

J.A. Silverman ◽

E. Franssen ◽

R. Buckstein ◽

K.R. Imrie

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Blood Cell ◽

Cell Count ◽

White Blood Cell Count ◽

White Blood Cell ◽

Lymphocytic Leukemia ◽

Blood Cell Count ◽

Marked Elevation

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A progressziómentes túlélést befolyásoló tényezők vizsgálata ibrutinibbel kezelt krónikus lymphoid leukémiás betegekben

Hematológia−Transzfuziológia ◽

10.1556/2068.2021.54.1.3 ◽

2021 ◽

Vol 54 (1) ◽

pp. 13-20

Author(s):

László Szerafin ◽

Péter Takács ◽

Gabriella Varjasi ◽

László Rejtő ◽

Péter Ilonczai ◽

...

Keyword(s):

Blood Cell ◽

Red Blood Cell ◽

Progression Free Survival ◽

Lymphocytic Leukemia ◽

Cell Distribution ◽

Lymphoid Leukemia ◽

Distribution Width ◽

Free Survival ◽

Factors Influencing ◽

Red Blood Cell Distribution

Összefoglaló. Bevezetés: A krónikus lymphoid leukémia kezelésében jelentős előrelépést eredményezett az ibrutinibterápia bevezetése. A gyógyszer első vonalbeli és többed vonalbeli kezelése is magas remissziós arányt eredményezett, bár a terápia korai bevezetése és a kedvező genetikai eltérések esetén az eredmények jobbak. A progressziómentes túlélést befolyásoló egyéb tényezőkről azonban még kevés adat áll rendelkezésre. Célkitűzés: Krónikus lymphoid leukémiás betegek ibrutinibkezelése során a teljes hematológiai remisszió elérését és a progressziómentes túlélés időtartamát befolyásoló tényezők vizsgálata. Betegek és módszer: 47 krónikus lymphoid leukémiás beteg (életkor: 39–84 év, férfi 27, nő 20, követési idő 5–58 hónap, medián 15 hónap) klinikai és laboratóriumi adatainak retrospektív elemzése. Eredmények: A teljes hematológiai remisszió elérése független volt a betegek nemétől, életkorától, a betegség stádiumától, az immunglobulin gén nehézlánc-variábilis régió státuszától, a genetikai aberrációktól, az abszolút neutrophilszámtól, az abszolút monocytaszámtól és a vörösvértestnagyság-eloszlási görbe szélességétől. A progressziómentes túlélést a komplett remisszió elérése (p = 0,00073) és a magasabb abszolút neutrophilszám (<4 G/l vs. ≥4 G/l, p = 0,022) befolyásolta szignifikánsan, a vörösvértestnagyság-eloszlási görbe szélességértékével való összefüggés pedig statisztikailag határértéken volt (p = 0,065). A Cox-féle regressziós elemzésbe bevont változók közül csak a teljes hematológiai remisszió elérése mutatott szignifikáns hatást a progressziómentes túlélésre (p = 0,0147). Következtetések: A teljes hematológiai remisszió elérése az egyéb vizsgált tényezőktől független, szignifikáns hatással bír a betegek progressziómentes túlélésére. Az abszolút neutrophilszám és a vörösvértestnagyság-eloszlási görbe szélessége szintén hasznos kiegészítő prognosztikus marker lehet. Az elemzett esetek száma még alacsony a komolyabb következtetések levonására, azonban így is elmondható, hogy az eredmények egy része már a szakirodalom korábbi eredményeit tükrözi. Summary. Introduction: The introduction of ibrutinib therapy has led to significant advances in the treatment of chronic lymphocytic leukemia. Both first-line and multiple-lines treatments of the drug resulted in high remission rates, although results were better with early initiation of therapy and favorable genetic abnormalities. However, little data are available on other factors influencing progression-free survival. Objective: To investigate factors influencing the achievement of complete hematological remission and progression-free survival with ibrutinib treatment in patients with chronic lymphocytic leukemia. Patients and metods: Retrospective analysis of clinical and laboratory data from 47 chronic lymphoid leukemia patients (age: 39–84 years, male 27, female 20, follow-up 5–58 months, median 15 months). Results: Achieving complete hematologic remission was independent of patient gender, age, disease stage, immunoglobulin heavy chain variable region status, genetic aberrations, absolute neutrophil count, absolute monocyte count, and red blood cell distribution width. Progression-free survival was significantly affected by complete remission (p = 0.00073), and higher absolute neutrophil counts (<4 G/l vs. ≥ 4 G/l, p = 0.022), the red blood cell distribution width was statistically less significant (p = 0.065). Of the variables included in the Cox regression analysis, only the achievement of complete hematologic remission had a significant effect on progression-free survival (p = 0.0147). Conclusions: Achieving complete hematologic remission, independent of the other factors studied, has a significant effect on patients’ progression-free survival. Absolute neutrophil count and red blood cell distribution width can also be a useful additional prognostic marker. The number of analyzed cases is still low to draw more serious conclusions, but it can still be said that some of the results already reflect previous results in the literature.

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High Aurora Kinase and Low Dido Levels Characterizes a Sub-Group of Chronic Lymphocytic Leukemia with Chromosomal Gains and High White Blood Cell Counts: Potential Inter-Regulatory Role of E2F1 and Mir-17-92 Cluster

Blood ◽

10.1182/blood.v128.22.2029.2029 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2029-2029

Author(s):

Felipe C Souza ◽

Josiane L Schiavinato ◽

Antonio R. Lucena-Araujo ◽

Fabio M Oliveira ◽

Amelia G Araújo ◽

...

Keyword(s):

Cell Cycle ◽

Chronic Lymphocytic Leukemia ◽

Blood Cell ◽

White Blood Cell ◽

Chromosomal Instability ◽

Regulatory Mechanism ◽

Lymphocytic Leukemia ◽

Transcript Levels ◽

Expression Levels

Abstract During cell cycle division Aurora kinases (AURKA and AURKB) participate in the formation and control of mitotic spindle fibers, while, protein isoforms (DIDO1, DIDO2 and DIDO3), derived by alternative splicing of the DIDO gene, assist at the junction of microtubules to kinetochores. Thus, both are relevant to cell cycle maintenance. Interestingly, overexpression (or gain of function) of AURKs or low expression (or loss of function of DIDO) are both associated with centrosomal amplification and chromosomal instability (CIN), leading to aneuploidy. Among hematological diseases with CIN records, chronic lymphocytic leukemia (CLL) can display centrosome amplification and changes in AURKs expression levels leading to aneuploidy. The Despite this, there are no studies evaluating the potential association of these genes with CIN in CLL. By evaluating their gene expression levels in CLL samples from patients with or without chromosomal aberrations, we show that increased levels of AURKA and AURKB and, conversely, reduced levels of DIDO variants, are both significantly associated with chromosomal gains and with increased white blood cell (WBC) counts. Clearly, CLL samples without any cytogenetic abnormality had expression levels similar to samples mostly harboring non-numerical aberrations. The finding that the expression levels of AURKs and DIDO variants are completely opposed, showing a discrete inter-related pattern, led us to investigate the potential regulatory mechanism behind this. Given that other have previously shown that the oncogenic miR-17-92 cluster is significantly upregulated in purified CLL patient cells expressing unmutated IGHV genes (as compared to mutated patient cells), and that miR-17 is expressed at significantly higher levels in unmutated or ZAP-70 high cases (bad prognostic cases generally associated with chromosomal instability), we investigated the potential negative regulation of DIDO variants by microRNAs from this cluster. In addition, based on the already described regulatory mechanism by which AURKA overexpression induces the E2F1-mediated transcription upregulation of the miR-17-92 cluster (with an observed expression correlation of both proteins in cancer specimens); we decided to investigate this regulatory axis in CLL. Notably, we found that all DIDO variants are predicted to be heavily targeted by several miRs of this oncogenic cluster. We show that CLL samples with low DIDO expression, in addition to the already mentioned AURK high levels, displayed significant higher levels of the transcription factor E2F1 and of its transcriptional target, the miR-17-92 primary transcript (MIR17HG). Moreover, by using the NTERA-2 cell line as a model, we show that siRNA knockdown of AURKA (at the transcript and protein level, as confirmed by qPCR and western blot) is accompanied by a striking significant reduction of E2F1 and also of MIR17HG. Furthermore, transfection of NTERA-2 cells with synthetic mimics of the miR-17~92 cluster (namely, miR-19a, miR-20a and miR-92a) results in a clear and significant reduction in the transcript levels of all DIDO variants. Finally, specific siRNA inhibition of the DIDO3 variant (but not the others) led to a significant reduction in the transcript levels of all DIDO variants, indicating an additional mechanism contributing to the downregulation of DIDO transcripts. Altogether, our results demonstrate the existence of a potential interconnected regulatory mechanism between AURK and DIDO, associated with CIN and higher WBC counts in CLL. More importantly, the high expression levels of AURKs and the associated low levels of DIDO variants are specifically associated with cytogenetic abnormalities presenting chromosomal gains, highlighting the specific cellular mechanism underlying the CIN observed in this distinct CLL group. Given the central role of CIN in cancer genesis and progression, these findings will likely have an important impact on prognosis or treatment of CLL. Funded by: FAPESP, CNPq and CAPES. Disclosures No relevant conflicts of interest to declare.

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Risk Factors of White Blood Cell Progression Among Patients With Chronic Lymphocytic Leukemia at Felege Hiwot Referral Hospital, Bahir Dar, Ethiopia

Cancer Informatics ◽

10.1177/11769351211069902 ◽

2022 ◽

Vol 21 ◽

pp. 117693512110699

Author(s):

Gedam Derbew Addisia ◽

Awoke Seyoum Tegegne ◽

Denekew Bitew Belay ◽

Mitiku Wale Muluneh ◽

Mahider Abere Kassaw

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Blood Cell ◽

White Blood Cell ◽

Blood Cells ◽

White Blood Cells ◽

Lymphocytic Leukemia ◽

Bahir Dar ◽

Felege Hiwot Referral Hospital ◽

Wbc Count

Background: Leukemia is a type of cancers that start in the bone marrow and produce a serious number of abnormal white blood cells. Bleeding and bruising problems, fatigue, fever, and an increased risk of infection are among symptoms of the disease. The main objective of this study is to identify the determinant of the progression rate of white blood cells among patients with chronic lymphocytic leukemia at Felege Hiwot Referral Hospital (FHRH), Bahir Dar, Ethiopia. Methods: A retrospective study design was conducted on 312 patients with chronic lymphocytic leukemia at FHRH, Bahir Dar, Ethiopia under treatment from 1 January 2017 to 31 December 2019. A linear mixed-effects model was considered for the progression of the white blood cell data. Results: The estimated coefficient of the fixed effect intercept was 84.68, indicating that the average white blood cell (WBC) count of the patients was 84.68 at baseline time by excluding all covariates in the model ( P-value <.001). Male sex ( β = 2.92, 95% confidence interval [CI] 0.58, 0.5.25), age ( β = .17, 95% CI 0.08, 0.28), widowed/divorced marital status ( β = 3.30, 95% CI 0.03, 6.57), medium chronic lymphocytic leukemia (CLL) stage ( β = −4.34, 95% CI −6.57, −2.68), high CLL stage ( β = −2.76, 95% CI −4.86, −0.67), hemoglobin ( β = .15, 95% CI 0.07, 0.22), platelet ( β = .09, 95% CI 0.02, 0.17), lymphocytes ( β = .16, 95% CI 0.03, 0.29), red blood cell (RBC) ( β = .17, 95% CI 0.09, 0.25), and follow-up time ( β = .27, 95% CI 0.19, 0.36) were significantly associated with the average WBC count of chronic lymphocytic leukemia patients. Conclusions: The finding showed that age, sex, lymphocytic, stage of chronic lymphocytic leukemia, marital status, platelet, hemoglobin, RBC, and follow-up time were significantly associated with the average WBC count of chronic lymphocytic leukemia patients. Therefore, health care providers should give due attention and prioritize those identified factors and give frequent counseling about improving the health of chronic lymphocytic leukemia patients.

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