Diagnosis, Differential Diagnosis, Prognosis and Treatment of Chronic Lymphoblastic Leukemia (CLL)
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This article provides a detailed overview of the diagnosis, differential diagnosis, prognosis, and treatment of Chronic Lymphoblastic Leukemia (CLL). It covers the symptoms, tests, and treatment options available for CLL. The article also discusses the prognostic factors that determine the survival chances of patients with CLL.
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1
Chronic Lymphoblastic Leukemia (CLL)
Diagnosis
Exclusionary Diagnosis
A 69-year-old man arrived at the GP clinic with symptoms like a dry cough, breath
shortness, and fatigue. His lymph nodes at the cervical region have enlarged in the previous six
weeks. Before the signs, he was healthy and conducted a regular exercise. Additional diagnosis
indicates that the patient lacks a family history of CLL. The patient has been well and has not
visited the hospital for over five years. Additionally, his erythropoietin sedimentation rate and C-
reactive protein levels are reasonable. These negative results prompt the physicians to carry out
physical tests to confirm the presence of the complication.
Differential diagnosis
The patient's blood tests indicate that he has CLL. The levels of White Blood Cells (WBC) and
Lymphocytes are higher in the normal ranges. An elevation in the count of WBC and B-cells
(lymphocytes) is an indication of the complication1. The patient also exhibits low RBC, HCT,
hemoglobin, and platelets. Patients with leukemia exhibit low cellular counts of platelets and
RBC.
The peripheral blood smear indicates many abnormal lymphocytes known as the smudge
cells which are an indication of the disease. Bone marrow tests also help to check for the
progression of the disease. The physician extracts samples from the hip bone. A close
examination of the bone marrow biopsy indicates mature blood cells which are a characteristic of
CLL2. The pictogram in the case study also demonstrates that the bone marrow has many blood-
forming cells. Therefore, the marrow of the patient is hypercellular. The patient's bone marrow
has more than twenty percent abnormal cells.
Chronic Lymphoblastic Leukemia (CLL)
Diagnosis
Exclusionary Diagnosis
A 69-year-old man arrived at the GP clinic with symptoms like a dry cough, breath
shortness, and fatigue. His lymph nodes at the cervical region have enlarged in the previous six
weeks. Before the signs, he was healthy and conducted a regular exercise. Additional diagnosis
indicates that the patient lacks a family history of CLL. The patient has been well and has not
visited the hospital for over five years. Additionally, his erythropoietin sedimentation rate and C-
reactive protein levels are reasonable. These negative results prompt the physicians to carry out
physical tests to confirm the presence of the complication.
Differential diagnosis
The patient's blood tests indicate that he has CLL. The levels of White Blood Cells (WBC) and
Lymphocytes are higher in the normal ranges. An elevation in the count of WBC and B-cells
(lymphocytes) is an indication of the complication1. The patient also exhibits low RBC, HCT,
hemoglobin, and platelets. Patients with leukemia exhibit low cellular counts of platelets and
RBC.
The peripheral blood smear indicates many abnormal lymphocytes known as the smudge
cells which are an indication of the disease. Bone marrow tests also help to check for the
progression of the disease. The physician extracts samples from the hip bone. A close
examination of the bone marrow biopsy indicates mature blood cells which are a characteristic of
CLL2. The pictogram in the case study also demonstrates that the bone marrow has many blood-
forming cells. Therefore, the marrow of the patient is hypercellular. The patient's bone marrow
has more than twenty percent abnormal cells.
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2
Bone marrows of normal individuals exhibit cells in a nodular pattern. However, CLL
marrows exist in the diffuse pattern. The cells of the marrow in the case study are spread
throughout the sample of the patient showing the signs of CLL. Stains and antibody
examinations such as immunocytochemistry, cytochemistry, and immunohistochemistry are
applicable with samples of bone marrow to test for the condition3. Physicians in the case study
applied monoclonal antibodies to examine the marrow of the patient. CLL patients have an
elevated number of CD23+, CD5+, and other B-lymphocytes cells. The case study indicates that
the patient has a large population of Ig-kappa, CD5+, CD19+, CD23+, and CD22+. Other cells that
exist in high numbers in the patient are the Bcl-2 and K-67+.
Cytogenetic analysis indicates the deletion of 11q in the case study which is an indication of
CLL. Physicians conduct tests to confirm the appearance of specific proteins and genes in the
cells of the Leukemia. The microscopic examination also checks for chromosomal changes in the
affected cells. Specialists apply techniques such as F.I.S.H and P.C.R to detect genetic
alterations4. Apart from the deletion of chromosome 11q, the complication deletes 13q and 17p.
Other cases indicate trisomy at chromosome 12; however, the patient in the case study lacks an
extra chromosome. The patient can undergo treatment to correct his situation since only
chromosome 11q has undergone deletion. The clinical presentation indicates that the patient has
CLL caused by the gene mutation.
Prognosis
Patients of CLL like the 69-year-old client in the case study always ask caregivers about
their survival and prognosis. The chances of an individual to survive the disease depend on
numerous risk factors. The prognostic determinants include the type of leukemia, medical
history, and stage of infection. The treatment method and the response of the patient to treatment
Bone marrows of normal individuals exhibit cells in a nodular pattern. However, CLL
marrows exist in the diffuse pattern. The cells of the marrow in the case study are spread
throughout the sample of the patient showing the signs of CLL. Stains and antibody
examinations such as immunocytochemistry, cytochemistry, and immunohistochemistry are
applicable with samples of bone marrow to test for the condition3. Physicians in the case study
applied monoclonal antibodies to examine the marrow of the patient. CLL patients have an
elevated number of CD23+, CD5+, and other B-lymphocytes cells. The case study indicates that
the patient has a large population of Ig-kappa, CD5+, CD19+, CD23+, and CD22+. Other cells that
exist in high numbers in the patient are the Bcl-2 and K-67+.
Cytogenetic analysis indicates the deletion of 11q in the case study which is an indication of
CLL. Physicians conduct tests to confirm the appearance of specific proteins and genes in the
cells of the Leukemia. The microscopic examination also checks for chromosomal changes in the
affected cells. Specialists apply techniques such as F.I.S.H and P.C.R to detect genetic
alterations4. Apart from the deletion of chromosome 11q, the complication deletes 13q and 17p.
Other cases indicate trisomy at chromosome 12; however, the patient in the case study lacks an
extra chromosome. The patient can undergo treatment to correct his situation since only
chromosome 11q has undergone deletion. The clinical presentation indicates that the patient has
CLL caused by the gene mutation.
Prognosis
Patients of CLL like the 69-year-old client in the case study always ask caregivers about
their survival and prognosis. The chances of an individual to survive the disease depend on
numerous risk factors. The prognostic determinants include the type of leukemia, medical
history, and stage of infection. The treatment method and the response of the patient to treatment
3
are also key prognostic factors. Prognosis refers to the estimation of the effects of a disease on a
patient by a health specialist. The physician examines the nature of the disease and the
characteristics of the patient before starting the prognosis.
The first prognostic determinant is the stage of the CLL. The patient’s condition is in the
late stages of development making it a less manageable situation. A low stage during diagnosis is
a favorable factor of prognosis. The pattern of the leukemia cells is another essential factor. The
cells in the patient’s bone marrow have the diffuse pattern which is a dangerous prognostic sign5.
Patients with nodular cell patterns have favorable factors of prognosis. Age of the patient also
determines the survival chances and prognosis. The patient is 69 years old which is an uncertain
prognosis. Patients below the age of fifty have a favorable prognosis.
Sex, chromosomal changes, and prolymphocytic transformation are other prognosis
factors. Women have desirable prognosis and survival chances than men. The patient in the case
study is male; hence, his prognosis is unfavorable. Deletion of a section of the 13th chromosome
is a desirable prognostic determinant if the rest of the chromosomes lack abnormalities6.
However, deletion of segments of chromosome 17 or 11 presents a less desirable prognostic
factor. Therefore, the patient has low survival chances due to the deletion of chromosome 11q.
An elevation in the number of lymphocytes is an adverse prognostic factor. The patient has a
high count of lymphocytes and WBC, thus, low chances of survival.
The time that the lymphocytes take to double up and the affected section of the affected
lymphocyte tissue are essential prognostic factors. Additionally, the levels of specific proteins
are also a prognostic determinant. Lymphocytes that double after six months create a more
crucial prognostic factor than those that take little time. The cells of the patients in the case study
have doubled after six weeks, thus, reducing his survival chances. The patient has a high level of
are also key prognostic factors. Prognosis refers to the estimation of the effects of a disease on a
patient by a health specialist. The physician examines the nature of the disease and the
characteristics of the patient before starting the prognosis.
The first prognostic determinant is the stage of the CLL. The patient’s condition is in the
late stages of development making it a less manageable situation. A low stage during diagnosis is
a favorable factor of prognosis. The pattern of the leukemia cells is another essential factor. The
cells in the patient’s bone marrow have the diffuse pattern which is a dangerous prognostic sign5.
Patients with nodular cell patterns have favorable factors of prognosis. Age of the patient also
determines the survival chances and prognosis. The patient is 69 years old which is an uncertain
prognosis. Patients below the age of fifty have a favorable prognosis.
Sex, chromosomal changes, and prolymphocytic transformation are other prognosis
factors. Women have desirable prognosis and survival chances than men. The patient in the case
study is male; hence, his prognosis is unfavorable. Deletion of a section of the 13th chromosome
is a desirable prognostic determinant if the rest of the chromosomes lack abnormalities6.
However, deletion of segments of chromosome 17 or 11 presents a less desirable prognostic
factor. Therefore, the patient has low survival chances due to the deletion of chromosome 11q.
An elevation in the number of lymphocytes is an adverse prognostic factor. The patient has a
high count of lymphocytes and WBC, thus, low chances of survival.
The time that the lymphocytes take to double up and the affected section of the affected
lymphocyte tissue are essential prognostic factors. Additionally, the levels of specific proteins
are also a prognostic determinant. Lymphocytes that double after six months create a more
crucial prognostic factor than those that take little time. The cells of the patients in the case study
have doubled after six weeks, thus, reducing his survival chances. The patient has a high level of
4
Bcl-2 which is an unsuitable prognostic factor. The disease has only affected his lymph nodes,
thus, presenting a suitable prognosis.
Gene mutations, Richter’s syndrome, and status of performance are the other prognostic
determinants. CLL cells that have undergone IGHV mutation have appropriate prognosis7. The
cells of the patient have not undergone the modification leaving him with inconvenient
prognosis. Patients with Richter transformation have adverse prognostic factors. However, the
patient lacks the mutation; thus, he has high survival chances. Individuals with desirable
performance status during diagnosis have favorable prognostic outcomes. Therefore, the patient
has a suitable prognosis due to his performance. Patients should visit the physicians regularly to
prevent late diagnosis.
Treatment
Chemotherapy is an ideal management remedy for CLL. The chemical-based therapy
kills the rapidly growing cells such as the lymphatic cells8. The patient has reported enlargement
of the lymph nodes in his cervical area. The physicians can administer the remedy through the
vein or in the form of pills. The stage of CLL infection determines the kind of chemotherapy
drug that a patient gets from the caregiver. The patient’s CLL is at an advanced stage; hence
require a combined therapy of drugs. However, early stages of the complication call for single
drug chemotherapy. Examples of the drugs include Ibrutinib and Bendamustine. The physicians
always combine rituximab and fludarabine for patients in advanced stages of CLL infection.
Surgery is also useful to remove an overgrown cell in the system of the patient. The 69
years old patient has enlarged lymph nodes that physicians can remove through surgical
operations. Radiations can also help to destroy the large lymphatic cells. The specialists should
direct a low-dosage of the radiations to protect normal cells9. The patient's spleen is of average
Bcl-2 which is an unsuitable prognostic factor. The disease has only affected his lymph nodes,
thus, presenting a suitable prognosis.
Gene mutations, Richter’s syndrome, and status of performance are the other prognostic
determinants. CLL cells that have undergone IGHV mutation have appropriate prognosis7. The
cells of the patient have not undergone the modification leaving him with inconvenient
prognosis. Patients with Richter transformation have adverse prognostic factors. However, the
patient lacks the mutation; thus, he has high survival chances. Individuals with desirable
performance status during diagnosis have favorable prognostic outcomes. Therefore, the patient
has a suitable prognosis due to his performance. Patients should visit the physicians regularly to
prevent late diagnosis.
Treatment
Chemotherapy is an ideal management remedy for CLL. The chemical-based therapy
kills the rapidly growing cells such as the lymphatic cells8. The patient has reported enlargement
of the lymph nodes in his cervical area. The physicians can administer the remedy through the
vein or in the form of pills. The stage of CLL infection determines the kind of chemotherapy
drug that a patient gets from the caregiver. The patient’s CLL is at an advanced stage; hence
require a combined therapy of drugs. However, early stages of the complication call for single
drug chemotherapy. Examples of the drugs include Ibrutinib and Bendamustine. The physicians
always combine rituximab and fludarabine for patients in advanced stages of CLL infection.
Surgery is also useful to remove an overgrown cell in the system of the patient. The 69
years old patient has enlarged lymph nodes that physicians can remove through surgical
operations. Radiations can also help to destroy the large lymphatic cells. The specialists should
direct a low-dosage of the radiations to protect normal cells9. The patient's spleen is of average
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5
size and does not require an operation. However, splenectomy assists in the removal of an
enlarged spleen. Surgery is efficient in younger patients than in older individuals like the male
client in the case study.
Leukapheresis lowers the blood levels of leukemic cells. The patient has a high cell count of
WBC and lymphocytes which is responsible for symptoms such as fatigue10. The removal of
cells such as Bcl-2 reduces the cell count of both lymphocytes and WBC. The impact of
leukapheresis is short lived but helps the patient to wait for the effects of chemotherapy. An
elevation in the amounts of the affected cells calls for the combination of leukapheresis with
chemotherapy.
The transplant of the bone marrow replaces the defective one with healthy bone marrow.
The cells in the patient's marrow exhibit the diffuse pattern instead of the desired pattern. The
transplant applies chemotherapy drugs to destroy cells that affect the lymphocytes11. The
specialists then infuse the healthy stem cells into the recipient's blood from the donor. However,
the invention of potent chemotherapy drugs is slowly taking the place of transplant. Patients of
advanced age prefer a bone marrow transplant to surgery. Additionally, the side effects of a
particular combination of drugs force specific patients to prefer organ transplant.
Immunotherapy is another remedy that can treat CLL. The intervention uses the immune
system of the patient to fight the disease12. The biopsy of the patient’s bone marrow indicates an
abnormal growth of cells. Immunotherapy enables the immune system of the affected individual
to detect and destroy malignant cells. The patient is complaining of fatigue that is worsening
each day. The remedies for fatigue include massage and regular physical exercise. The
application of meditation techniques also helps to relieve an individual from fatigue. The patient
can also perform yoga to improve his condition when the other methods fail.
size and does not require an operation. However, splenectomy assists in the removal of an
enlarged spleen. Surgery is efficient in younger patients than in older individuals like the male
client in the case study.
Leukapheresis lowers the blood levels of leukemic cells. The patient has a high cell count of
WBC and lymphocytes which is responsible for symptoms such as fatigue10. The removal of
cells such as Bcl-2 reduces the cell count of both lymphocytes and WBC. The impact of
leukapheresis is short lived but helps the patient to wait for the effects of chemotherapy. An
elevation in the amounts of the affected cells calls for the combination of leukapheresis with
chemotherapy.
The transplant of the bone marrow replaces the defective one with healthy bone marrow.
The cells in the patient's marrow exhibit the diffuse pattern instead of the desired pattern. The
transplant applies chemotherapy drugs to destroy cells that affect the lymphocytes11. The
specialists then infuse the healthy stem cells into the recipient's blood from the donor. However,
the invention of potent chemotherapy drugs is slowly taking the place of transplant. Patients of
advanced age prefer a bone marrow transplant to surgery. Additionally, the side effects of a
particular combination of drugs force specific patients to prefer organ transplant.
Immunotherapy is another remedy that can treat CLL. The intervention uses the immune
system of the patient to fight the disease12. The biopsy of the patient’s bone marrow indicates an
abnormal growth of cells. Immunotherapy enables the immune system of the affected individual
to detect and destroy malignant cells. The patient is complaining of fatigue that is worsening
each day. The remedies for fatigue include massage and regular physical exercise. The
application of meditation techniques also helps to relieve an individual from fatigue. The patient
can also perform yoga to improve his condition when the other methods fail.
6
References
1. O'Brien SM, Lamanna N, Kipps TJ, Flinn I, Zelenetz AD, Burger JA, Keating M, Mitra
S, Holes L, Albert SY, Johnson DM. A phase 2 study of idelalisib plus rituximab in
treatment-naive older patients with chronic lymphocytic leukemia. Blood. 2015 Jan
1:blood-2015.
2. Thompson PA, Tam CS, O'Brien SM, Wierda WG, Stingo F, Plunkett W, Smith SC,
Kantarjian HM, Freireich EJ, Keating MJ. Fludarabine, cyclophosphamide, and rituximab
achieve long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia.
Blood. 2015 Jan 1:blood-2015.
3. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD,
Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization (WHO)
classification of myeloid neoplasms and acute leukemia. Blood. 2016 Jan 1:blood-2016.
4. Cao, B., Wei, P., Liu, Z., Bi, R., Lu, Y., Zhang, L., ... & Zhou, X. (2016). Detection of
lung adenocarcinoma with ROS1 rearrangement by IHC, FISH, and RT-PCR and
analysis of its clinicopathologic features. OncoTargets and therapy, 9, 131.
5. Kipps TJ, Stevenson FK, Wu CJ, Croce CM, Packham G, Wierda WG, O'Brien S,
Gribben J, Rai K. Chronic lymphocytic leukemia. Nature reviews Disease primers. 2017
Jan 19;3:16096.
6. Baliakas P, Hadzidimitriou A, Sutton LA, Rossi D, Minga E, Villamor N, Larrayoz M,
Kminkova J, Agathangelidis A, Davis Z, Tausch E. Recurrent mutations refine prognosis
in chronic lymphocytic leukemia. Leukemia. 2015 Feb;29(2):329.
References
1. O'Brien SM, Lamanna N, Kipps TJ, Flinn I, Zelenetz AD, Burger JA, Keating M, Mitra
S, Holes L, Albert SY, Johnson DM. A phase 2 study of idelalisib plus rituximab in
treatment-naive older patients with chronic lymphocytic leukemia. Blood. 2015 Jan
1:blood-2015.
2. Thompson PA, Tam CS, O'Brien SM, Wierda WG, Stingo F, Plunkett W, Smith SC,
Kantarjian HM, Freireich EJ, Keating MJ. Fludarabine, cyclophosphamide, and rituximab
achieve long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia.
Blood. 2015 Jan 1:blood-2015.
3. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD,
Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization (WHO)
classification of myeloid neoplasms and acute leukemia. Blood. 2016 Jan 1:blood-2016.
4. Cao, B., Wei, P., Liu, Z., Bi, R., Lu, Y., Zhang, L., ... & Zhou, X. (2016). Detection of
lung adenocarcinoma with ROS1 rearrangement by IHC, FISH, and RT-PCR and
analysis of its clinicopathologic features. OncoTargets and therapy, 9, 131.
5. Kipps TJ, Stevenson FK, Wu CJ, Croce CM, Packham G, Wierda WG, O'Brien S,
Gribben J, Rai K. Chronic lymphocytic leukemia. Nature reviews Disease primers. 2017
Jan 19;3:16096.
6. Baliakas P, Hadzidimitriou A, Sutton LA, Rossi D, Minga E, Villamor N, Larrayoz M,
Kminkova J, Agathangelidis A, Davis Z, Tausch E. Recurrent mutations refine prognosis
in chronic lymphocytic leukemia. Leukemia. 2015 Feb;29(2):329.
7
7. Jain P, Keating M, Wierda W, Estrov Z, Ferrajoli A, Jain N, George B, James D,
Kantarjian H, Burger J, O'Brien S. Outcomes of patients with chronic lymphocytic
leukemia (CLL) after discontinuing ibrutinib. Blood. 2015 Jan 1:blood-2014.
8. Kantarjian H, Stein A, Gökbuget N, Fielding AK, Schuh AC, Ribera JM, Wei A,
Dombret H, Foà R, Bassan R, Arslan Ö. Blinatumomab versus chemotherapy for
advanced acute lymphoblastic leukemia. New England Journal of Medicine. 2017 Mar
2;376(9):836-47.
9. DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, Alteri R, Robbins
AS, Jemal A. Cancer treatment and survivorship statistics, 2014. CA: a cancer journal for
clinicians. 2014 Jul;64(4):252-71.
10. June CH, Levine BL, Chew A, Schuster SJ, inventors; University of Pennsylvania,
assignee. Methods for treating chronic lymphocytic leukemia (CLL). The United States
patent application US 10/046,008. 2018 Aug 14.
11. Eichhorst B, Robak T, Montserrat E, Ghia P, Hillmen P, Hallek M, Buske C. Chronic
lymphocytic leukemia: ESMO Clinical Practice Guidelines for diagnosis, treatment, and
follow-up. Annals of Oncology. 2015 Aug 25;26(suppl_5):v78-84.
12. Stickel J, Kowalewski D, Rammensee HG, Stevanovic S, inventors; Immatics
Biotechnologies GmbH, assignee. Immunotherapy against several tumors of the blood, in
particular, chronic lymphoid leukemia (CLL). The United States patent application US
10/000,533. 2018 Jun 19.
7. Jain P, Keating M, Wierda W, Estrov Z, Ferrajoli A, Jain N, George B, James D,
Kantarjian H, Burger J, O'Brien S. Outcomes of patients with chronic lymphocytic
leukemia (CLL) after discontinuing ibrutinib. Blood. 2015 Jan 1:blood-2014.
8. Kantarjian H, Stein A, Gökbuget N, Fielding AK, Schuh AC, Ribera JM, Wei A,
Dombret H, Foà R, Bassan R, Arslan Ö. Blinatumomab versus chemotherapy for
advanced acute lymphoblastic leukemia. New England Journal of Medicine. 2017 Mar
2;376(9):836-47.
9. DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, Alteri R, Robbins
AS, Jemal A. Cancer treatment and survivorship statistics, 2014. CA: a cancer journal for
clinicians. 2014 Jul;64(4):252-71.
10. June CH, Levine BL, Chew A, Schuster SJ, inventors; University of Pennsylvania,
assignee. Methods for treating chronic lymphocytic leukemia (CLL). The United States
patent application US 10/046,008. 2018 Aug 14.
11. Eichhorst B, Robak T, Montserrat E, Ghia P, Hillmen P, Hallek M, Buske C. Chronic
lymphocytic leukemia: ESMO Clinical Practice Guidelines for diagnosis, treatment, and
follow-up. Annals of Oncology. 2015 Aug 25;26(suppl_5):v78-84.
12. Stickel J, Kowalewski D, Rammensee HG, Stevanovic S, inventors; Immatics
Biotechnologies GmbH, assignee. Immunotherapy against several tumors of the blood, in
particular, chronic lymphoid leukemia (CLL). The United States patent application US
10/000,533. 2018 Jun 19.
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