Leukemia

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Continuing Education Activity

Leukemia is a heterogeneous group of hematologic malignancies that arise from the dysfunctional proliferation of developing leukocytes. It is classified as either acute or chronic and as myelocytic or lymphocytic. Treatment depends on the type of leukemia but generally involves chemotherapy. This activity reviews the evaluation and treatment of leukemia and highlights the role of the interprofessional team in evaluating and treating patients with this condition. This activity describes the evaluation and management of leukemia and reviews the role of the interprofessional team in improving care for patients with this condition.

Objectives:

  • Identify the epidemiology of leukemia.
  • Review the appropriate evaluation of leukemia.
  • Outline the management options available for leukemia.
  • Describe interprofessional team strategies for improving care coordination and communication when treating patients with leukemia.

Introduction

Leukemia is a production of abnormal leukocytes either as a primary or secondary process. Based on the rapidity of proliferation, they can be classified as acute or chronic, and myeloid or lymphoid based on the originator cell. Predominant subtypes are acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), involving the myeloid chain; and acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL) involving the lymphoid chain. Other less common variants such as mature B-cell and T-cell leukemias, NK cell-related leukemias, to name a few, arise from mature WBC cells. However, with the advent of next-generation sequencing (NGS) and identification of various biomarkers, the World Health Organization (WHO) classification was updated in 2016, bringing multiple changes to the traditional classification for AML, myelodysplastic/myeloproliferative neoplasms (MDS/MPN).[1] GLOBOCAN, which is a global observatory for cancer trends, showed the global incidence of 474,519 cases with 67,784 in North America. The Age-Standardized Rates are around 11 per 100000, with a mortality rate of approximately 3.2.[2]

Many genetic risk factors have been identified, such as Klinefelter and Down syndromes, ataxia telangiectasia, Bloom syndrome, and telomereopathies such as Fanconi anemia, dyskeratosis congenita, and Shwachman-Diamond syndrome; germline mutations in RUNX1, CEBPA, to name a few. Viral infections from Epstein Barr virus, Human T-lymphotropic virus, ionizing radiation exposure, radiation therapy, environmental exposure with benzene, smoking history, history of chemotherapy with alkylating agents, topoisomerase II agents. Symptoms are nonspecific and can include fever, fatigue, weight loss, bone pain, bruising, or bleeding. Definitive diagnoses often require bone marrow biopsy, the results of which inform interprofessional treatment ranging from chemotherapy to stem cell transplantation. Prognosis is variable depending on the leukemia subtype in question.

Acute vs. chronic: Blasts, which are immature and dysfunctional cells, normally make up 1% to 5% of marrow cells. Acute leukemias are characterized by greater than 20% blasts in the peripheral blood smear or on bone marrow leading to a more rapid onset of symptoms. In contrast, chronic leukemia has less than 20% blasts with a relatively chronic onset of symptoms. The accelerated/blast phase is a transformation of chronic leukemia into an acute phase with a significantly higher degree of blasts.[1][3][4]

As such, the four major subtypes of leukemia are:

  • Acute lymphoblastic leukemia (ALL): ALL is seen in patients with the blastic transformation of B and T cells. It is the most common leukemia in pediatrics, accounting for up to 80% of cases in this group vs. 20% of cases in adults. Treatment among young adults is predominantly inspired by pediatric regimens with better survival rates.  
  • Acute myelogenous leukemia (AML): AML is characterized by greater than 20% myeloid blasts and is the most common acute leukemia in adults. It is the most aggressive cancer with a variable prognosis depending upon the molecular subtypes. 
  • Chronic lymphocytic leukemia (CLL): CLL occurs from the proliferation of monoclonal lymphoid cells. Most cases occur in people between ages 60 and 70. 
  • Chronic myelogenous leukemia (CML): CML typically arises from reciprocal translocation and fusion of BCR on chromosome 22 and ABL1 on chromosome 9, resulting in dysregulated tyrosine kinase on chromosome 22 called the Philadelphia chromosome. This, in turn, causes a monoclonal population of dysfunctional granulocytes, predominantly neutrophils, basophils, and eosinophils.[1][3][5][6]

Etiology

Multiple genetic and environmental risk factors are identified in the development of leukemia. 

  • Exposure to ionizing radiation is associated with an increased risk of multiple subtypes of leukemia.[7][8]
  • Exposure to benzene is a risk factor for leukemia in adults, particularly AML.[9] 
  • Previous exposure to chemotherapy, especially alkylating agents and topoisomerase inhibitors, increases the risk for acute leukemia later in life.[7][8]
  • A history of any hematologic malignancy is a risk factor for subsequently developing another subtype of leukemia.[10]
  • Viral infections (e.g., human T-cell leukemia virus, Epstein Barr virus) are linked with subtypes of ALL.[11]
  • Several genetic syndromes (e.g., Down syndrome, Fanconi anemia, Bloom syndrome, Li-Fraumeni syndrome) are associated with an increased risk of AML and ALL.[12]

Epidemiology

GLOBOCAN, which is a global observatory for cancer trends, showed the global incidence of 474,519 cases with 67,784 in North America. The Age-Standardized Rates are around 11 per 100000 with a mortality rate of about 3.2. ALL and AML, which are important diseases in both childhood and adulthood, have bimodal age distributions with CML and CLL mostly in the older age groups. According to SEER data, there are 61,090 estimated new cases of leukemia in 2021, accounting for 3.2% of all new cancer cases, making leukemia, 10th most common cancer in the United States. Estimated deaths are about 23,660, which comprises 3.9% of all cancer deaths. Since 2006, the incidence of the disease has increased by an average of 0.6% per year, while the mortality has decreased by an annual average of 1.5%.[6][7]

Pathophysiology

Leukemia occurs due to the malignant transformation of pluripotent (i.e., can give rise to both myeloid and lymphoid precursors) hematopoietic stem cells. Rarely, it can also involve a more committed stem cell that has a limited self-renewal capacity. In acute leukemias, these malignant cells are generally immature, poorly differentiated, abnormal leukocytes (blasts) that can either be lymphoblasts or myeloblasts. These blasts can undergo clonal expansion and proliferation, leading to replacement and interference of the development and the function of normal blood products with malignant cells, leading to clinical symptoms. 

Acute Leukemia

In ALL, chromosomal translocation or abnormal chromosome numbers can lead to mutations in precursor lymphoid cells leading to lymphoblasts. Common mutations include t(12;21) and t(9;22). In AML, chromosomal translocations, rearrangements, and gain or loss of chromosomes can lead to mutations and abnormal production of myeloblasts. One important translocation is t(15;17), which leads to the fusion of retinoic acid receptor alpha (RARA) and a promyelocytic leukemia transcription factor (PML). This leads to the development of acute promyelocytic leukemia, which can present with hallmarks of disseminated intravascular coagulation and need emergent treatment with retinoic acid.

Chronic Leukemia

Chromosomal abnormalities in hematopoietic stem cells that are precursors to leucocytes are the most common cause of chronic leukemia. Examples of abnormalities are deletions, translocations, or extra-chromosomes. In CML, mutations mostly affect granulocytes (most commonly the t(9;22) translocation), and in CLL, they mostly affect lymphocytes (especially B lymphocytes). Unlike acute leukemia, in chronic leukemia, cells are partially mature. These partially mature cells do not function effectively and divide too quickly. They accumulate in the peripheral blood and lymphoid organs, which can lead to anemia and thrombocytopenia, and leukopenia. 

Histopathology

Acute Leukemia

In acute leukemia, the peripheral blood or bone marrow is characterized by more than 20% blasts. However, regardless of the blast percentage, patients with translocation, t(8;21)(q22;q22); RUNX1-RUNX1T1, inversion -inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11 or translocation - t(15;17)(q24.1;q21.1); PML-RARA, are considered and treated as acute leukemia. There is usually increased bone marrow cellularity, packed with blasts and a variable number of granulocytic or monocytic cells and erythroid precursors. Traditional markers included in the evaluation are CD7, CD11b, CD13, CD14, CD15, CD16, CD33, CD34, CD45, CD56, CD117, HLA Dr. Also, either peripheral smear or bone marrow aspirate is sent for mutation panel of multiple genes which have therapeutic and prognostic implications such as ASXL1, CEBPA, DNMT3A, FLT3, IDH1, IDH2, NPM1, RUNX1, and TP53, to mention a few. 

There is also increased bone marrow cellularity in ALL, composed of B and T lymphoblasts (which have small nucleoli, dispersed chromatin, and cleaved and irregular nuclei with undetectable cytoplasm). Common T-cell lymphoid immunostains include: TdT, CD2, CD3, CD5, CD7. Common B-cell lymphoid immunostains include: HLA-DR, CD10, CD19, CD22, CD79a, PAX5, CD20. There should not be any myeloid markers such as MPO to confirm the diagnosis of the pure lymphoid lineage. Mixed phenotype acute leukemia (MPAL) has both myeloid and lymphoid markers but is a rare entity. Cytogenetics evaluation for Philadelphia chromosome (PH) status and PH-like translocation is a must as newer therapeutic agents are now incorporated into treatment algorithms.[13]

Chronic Leukemia

In chronic leukemia, the white blood cell count is often elevated, with smear suggestive of significant left shift/granulocyte predominance. Such a picture is commonly seen during the acute illness phase, but if such a picture persists upon repeat labs, CML should be evaluated. In CML, the translocation t(9;22) can be diagnostic by FISH on peripheral blood. Bone marrow biopsy is not necessary for diagnosis, but if done, it will show a 100% cellular marrow with increased granulocyte precursors, basophils, eosinophils, and occasional monocytes.

In CLL, the white cell count is elevated, with mostly CD5+, CD23+ B-lymphocytes. The absolute lymphocyte count (ALC) has to be > 5,000 for diagnosis. If the ALC is less than 5,000, the entity is termed monoclonal B cell lymphocytosis of undetermined significance. Flow cytometry is often diagnostic. Patients would need evaluation for Del(17p) and TP53 mutation status, Immunoglobulin heavy chain variable region (IGHV) gene mutation status, Del(11q), del(13q), and trisomy 12 for chemotherapy vs. first-line targeted therapy selection.[14]

History and Physical

Acute Leukemia

Acute leukemia tends to present non-specifically, although the most common presenting features include fever, lethargy, and bleeding. Hepatosplenomegaly, lymphadenopathy, and musculoskeletal symptoms (especially in the spine and long bones) can also be clues to the diagnosis. Adults may also have more prominent anemia-related symptoms, such as shortness of breath, or symptoms related to thrombocytopenia, such as excessive bruising or heavy menstrual cycles. 

Chronic Leukemia

Chronic leukemia subtypes occur almost exclusively in adults. Many patients are asymptomatic at the time of diagnosis, identified only incidentally after marked leukocytosis is discovered on a CBC performed for another reason. Hepatosplenomegaly and lymphadenopathy can be appreciated in some cases while bleeding and bruising are less common, presenting features relative to acute leukemia subtypes.[15]

Evaluation

The workup of leukemia is time-consuming, and multiple tests are needed to confirm a diagnosis, and subsequently, to stage the disease. Helpful initial studies include a complete blood count (CBC), complete metabolic panel (CMP), liver function test (LFT), and coagulation panel, which are often followed by a peripheral blood smear and a bone marrow specimen. 

On rare occasions, leukemia can be diagnosed on histology alone. For example, AML is characterized by the presence of Auer rods (red staining, needle-like bodies seen in the cytoplasm of myeloblasts) on a peripheral smear. In most other cases, more detailed analyses with flow cytometry, cytogenetic, and FISH testing – are required to distinguish between subtypes.[16]

A bone marrow aspiration and biopsy are often required for the diagnosis of acute leukemias. For chronic leukemias, peripheral blood evaluation is often enough, and an invasive bone marrow biopsy may not be needed. For example, CML can be diagnosed by looking for BCR-ABL fusion protein on peripheral blood FISH analysis. CLL can be diagnosed by looking for a monoclonal B-cell population by doing a peripheral blood flow cytometry.

Treatment / Management

Patients with leukemia should be referred to a hematologist-oncologist to initiate treatment. Therapy varies significantly based on the leukemia subtype and patient factors (e.g., age, comorbid conditions). Acute leukemias are treated predominantly as an in-patient needing significant support, frequent monitoring of vitals, assess infections and electrolyte imbalances. The predominant challenge at the time of diagnosis of acute myeloid leukemia is to identify the possibility of APL, which has significantly different treatment compared to the rest of AML.

APL: APL patients typically present with bleeding diathesis with increased coagulation parameters and low fibrinogen. Peripheral smear shows a predominance of myeloid blasts with Auer rods. It is important to start the treatment with ATRA (All trans-retinoic acid) when APL is suspected rather than awaiting confirmatory tests with FISH. ATRA advances arrested promyeloblasts from becoming mature granulocytes which can result in differentiation syndrome.[17] Differentiation syndrome is seen during 48 hours of ATRA initiation to even three weeks from starting therapy for APL. Patients have a fever, respiratory distress with acute pulmonary infiltration on imaging, and capillary leak resulting in edema. It can mimic sepsis, resulting in delaying the treatment with dexamethasone. The commonly accepted dosage is at 10mg every 12 hours till improvement in symptoms and counts[18]. Other important complication with ATRA includes raised intracranial pressure leading to headaches and significant vision changes from papilledema. 

Specific treatment for APL is dependent on weather patient is at low/intermediate risk [WBC count <10,000/ microL (≤10 x 10/L)] and high risk [WBC count >10,000/ microL (>10 x 10/L)]. 

  • Low-risk APL: Patients respond well to a non-chemotherapy regimen with ATRA and Arsenic trioxide (ATO) with lesser complications during induction and recovery without a need for Bone marrow transplant (BMT). During the utilization with ATO, patients need to be monitored for electrolyte changes closely and Electrocardiogram (EKG) for QTc prolongation (Framingham formula) [19]
  • High-risk APL: Along with ATRA + ATO, high-risk patients achieve better responses to the addition of idarubicin[20]. Recent studies have included CD33-targeted drug conjugate, gemtuzumab ozogamicin (GO), during the induction therapy combined with ATRA + ATO[21]

Patients have better overall survival and prognosis in comparison to other types of AML without needing a transplant. 

AML: Standard therapy for AML is well known as the '7+3' regimen, which includes a 7-day course of cytarabine continuous infusion with a 3-day course of anthracycline (either daunorubicin or idarubicin). With the advent of cytogenetics and NGS testing, patients are now being risk-stratified based on the molecular markers resulting in prognostic and therapeutic implications. The outline of therapy based on the risk status per ELN (European LeukemiaNet) [22] is as follows 

Risk Status Cytogenetics Treatment 
Favorable Risk t(8;21)(q22;q22.1); inv(16) or t(16;16)Mutated NPM1 without FLT3-ITD or with FLT3-ITDlowBiallelic mutated CEBPA

Standard 7+3 regimen with/without GO.[23]

This chemo regimen can be attempted in patients > 60years old if they have good tolerability. 

Patients who achieved complete response can complete consolidation without the obvious need for BMT unless patients relapse. 

Intermediate risk Mutated NPM1 and FLT3-ITDhighWild type NPM1 without FLT3-ITD or with FLT3-ITDlow (without adverse-risk genetic lesions)t(9;11)(p21.3;q23.3); MLLT3-KMT2ACytogenetic abnormalities not classified as favorable or adverse

 

Standard 7 + 3 with FLT3 tyrosine kinase inhibitor (midostaurin) during induction and consolidation.[24]

Strongly consider BMT among this risk group. 

 

For patients above 60 years or older

Hypomethylating agents (HMA) with/without B-cell lymphoma-2 (BCL-2) inhibitor - venetoclax.[25]

 

Therapy-related AML or AML from antecedent MDS (Myelodysplastic syndrome)  or CMML(Chronic myelomonocytic leukemia)

Patients have a better response with liposomal cytarabine and liposomal daunorubicin, which is a category 1 indication in NCCN guidelines.[26]

Adverse Risk t(6;9)(p23;q34.1); DEK-NUP214t(v;11q23.3); KMT2A rearrangedt(9;22)(q34.1;q11.2); BCR-ABL1inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2,MECOM(EVI1) –5 or del(5q); –7; –17/abn(17p)Complex karyotype,◊ monosomal karyotype§Wild type NPM1 and FLT3-ITDhighMutated RUNX1Mutated ASXL1Mutated TP53

ALL

ALL is divided into B or T lymphocyte variants based on the lymphoblast origin and the presence of > 20% lymphoblasts in peripheral smear or BM. The presence or absence of the Philadelphia chromosome (PH) is the most important molecular marker leading to therapeutic implications on the treatment of ALL. 

PH Status  Treatment Regimen
PH Positive ALL

Combination of chemotherapy with TKI favorably 2nd generation and beyond such as dasatinib, ponatinib, bosutinib, nilotinib, and imatinib. Not all the TKI combinations have data with chemotherapy agents, and availability of the drug and provider practices generally dictates the regimen. 

For patients in adolescent young adult age groups (around 15 to 40 years) - pediatric-inspired chemotherapy regimens with peg-asparaginase ( Berlin-Frankfurt-Münster ) are favored when patients can tolerate treatment.

Other chemotherapy options, including patients < 65 years old, include hyperfractionated CVAD( cyclophosphamide, vincristine sulfate, doxorubicin, and dexamethasone), alternating with high dose methotrexate and cytarabine, and newer therapy with bispecific CD19-directed CD3 T-cell engager (blinatumomab).[27][28][29]

For patients > 65 years old, TKI backbone combined with corticosteroids with/without vincristine or lower dose Hyper CVAD in robust patients can be tried.[30][28][30]

 

PH Negative ALL

 Chemotherapy forms the predominant backbone in PH-negative patients without any role for TKI's. Multiple chemotherapy regimens are adapted based on the age of the patient. 

Adolescent young adult group - Predominantly used peg-asparaginase-based regimens such as CALGB 10403, COG AALL0434, DCFI ALL regimen, etc.[31][32][33][32][31]

For patients less than 65 years old - Rituximab-based regimen in CD 20 positive patients such as GRAALL-2005 [34], CALGB 8811, and Hyper - CVAD as mentioned prior. 

For older patients, based on their performance status, corticosteroids with/without vincristine, POMP regimen (prednisolone, vincristine, methotrexate, and 6-mercaptopurine), and lower dose hyper-CVAD therapy are options.[35]

The overall outcome depends upon the patient's response to induction chemotherapy and the presence or absence of MRD (minimal residual disease ) needing further therapies and BMT. 

CML: CML is one of the first cancers revolutionized by utilizing targeted therapy with PH chromosome TKI's. Patients have a significant response to TKI's, negating the need for acute chemotherapy unless they are in an accelerated phase/blast crisis. Based on multiple calculators available such as Sokal score, EUTOS Score, and The EUTOS long-term survival score(ELTS), a patient's risk can be assessed.[36][37][38][37][36] For patients having high-risk disease, second-generation (nilotinib, dasatinib, and bosutinib) TKI's are utilized as first-line therapy to achieve the therapy milestones faster with deeper responses.[39] For low and intermediate-risk patients, imatinib can be initiated as first-line therapy. However, there is no significant difference in overall survival based on the generation of the TKI that is used. 

Major milestones after initiation of TKI include: 

  • At 3 months: BCR-ABL1 (International Scale [IS]) at ≤10 percent and/or ≤35 % PH positive metaphase cells
  • At 6 months: BCR-ABL1 (IS) at ≤1 percent or/and 0 % PH positive metaphase cells
  • At 1 year.   : BCR-ABL1 (IS) ≤0.1 percent 

Patients needed to be monitored for resistance mutations, predominantly T315I mutation, for which ponatinib is approved.[40] Patients might continue to develop resistance to multiple TKI's for whom BMT can be attempted. 

CLL: CLL runs its course in a more indolent fashion than all the other leukemic subtypes, with the patient's lifespan minimally impacted by the disease. Patients do not benefit from early treatment unless they meet the criteria for therapy. Patients with rapid doubling time of lymphocytes, worsening cytopenias, increasing spleen size causing abdominal discomfort, and significant B symptoms - fatigue, night sweats, and weight loss; benefit from treatment. The most important determinant in the treatment of CLL is to know the IGVH mutation status and presence of del17p and TP53 mutation. t(11:14) is often obtained to rule out mantle cell lymphoma. 

For patients with IGVH mutation who have a relatively good prognosis - chemotherapy with FCR (fludarabine, cyclophosphamide, rituximab)[41] or BR (bendamustine, rituximab)[42] can be attempted as patients would be able to achieve good medication-free years before relapse. For high-risk patients with del17p / TP53 mutation, patients benefit significantly from targeted therapy with venetoclax (BCL-2 inhibitor) or BTK inhibitors (ibrutinib, acalabrutinib), either as a single agent or in combination with rituximab or obinutuzumab.[43][44][45][46] Rarely do patients with CLL/SLL who have a dormant course present with acute aggressive lymphadenopathy. They need an urgent biopsy of the lymph node or bone marrow to rule out Richter transformation into aggressive diffuse large B cell lymphoma and rarely Hodgkin lymphoma and T cell lymphomas. 

Differential Diagnosis

Given that leukemia itself is a broad diagnosis with non-specific symptoms, the differential diagnosis is broad. One must rule out infection, drug effects, vitamin/micronutrient deficiencies, and other myelodysplastic disorders that can cause abnormalities in blood cell lines.  

Consider the following when seeing abnormalities in the blood count:

  • B12 and folate deficiencies
  • Copper deficiencies
  • Viral infections (e.g., HIV, cytomegalovirus, Epstein Barr virus) 
  • Drugs (chemotherapeutic agents, valproic acid, ganciclovir, mycophenolate mofetil) 
  • Autoimmune conditions (e.g., systemic lupus erythematosus)

Prognosis

Long-term survival with leukemia varies tremendously based on leukemia subtype, cytogenetic and molecular findings, patient age, and comorbid conditions. Broadly, the 5-year cancer survival rate for leukemia has increased from 33% in 1975 to 59% in 2005.[6]

Complications

Tumor Lysis Syndrome (TLS)

TLS is a complication of chemotherapy that can result when tumor cells die quickly. The widespread cellular destruction releases intracellular contents into the bloodstream overwhelming the kidneys, resulting in dangerously high serum levels of potassium, phosphorus, uric acid, and blood urea nitrogen.[47] patients need aggressive hydration, frequent lab monitoring, and management of hyperuricemia with allopurinol and rasburicase. Hyperkalemia and hypocalcemia can lead to significant cardiac toxicity requiring urgent correction. 

Disseminated Intravascular Coagulation (DIC)

DIC is a complication of leukemia itself in which the proteins that control blood clotting become overactive, leading to both thrombosis and hemorrhage. DIC is often associated with acute promyelocytic leukemia but can be seen in other subtypes of leukemia as well.[16]. Frequent lab monitoring with active replacement of fibrinogen with cryoprecipitate is vital to the survival of the patient. 

Infection

Immunosuppression from chemotherapy, stem cell transplantation, or leukemia itself increases the risk of dangerous infections. Fever with neutropenia in an immunosuppressed patient should prompt an immediate evaluation for infection source and the initiation of broad-spectrum antibiotic therapy.[48]

Cancer

Survivors of leukemia are at an increased risk of subsequent cancers. For example, the Childhood Cancer Survivor Study demonstrated that the 30-year cumulative incidence of any cancer after leukemia was 5.6%; the median time to occurrence of the subsequent cancer was nine years. The most common second neoplasms in childhood leukemia survivors are different subtypes of leukemia or lymphoma.[10]

Deterrence and Patient Education

Leukemia is the production of abnormal white blood cells from bone marrow and lymphatic tissues. Excess production of such white blood cells affects the production of normal blood cells, which are important to fight infections, carry oxygen, and help with clotting blood during a bleeding situation. Such abnormal cell production can be fast, making it acute leukemia or a relatively slower process leading to chronic leukemia. Common symptoms include recurrent infections, weight loss, fatigue, fevers, abdominal pain, and bleeding issues. Multiple different types of leukemias are present, and they require evaluation by a hematologist for further guidance on treatment. 

Enhancing Healthcare Team Outcomes

Acute and chronic leukemias are heterogeneous hematologic diseases with complex diagnostic and therapeutic requirements requiring an interdisciplinary team. The involvement of healthcare professionals from across specialties and disciplines - physicians, nurses, physical therapists, nutritionists, etc. - is needed to achieve effective management, mitigate adverse events, and ensure their quality of life. Patient-centered communication and shared decision-making are integral to successful patient outcomes.



(Click Image to Enlarge)
Blast crisis, Leukemia, CML
Blast crisis, Leukemia, CML
Contributed by Centers of Disease Control and Prevention (Public Domain)

(Click Image to Enlarge)
Hairy cell leukemia
Hairy cell leukemia
Image courtesy S Bhimji MD

(Click Image to Enlarge)
Bone marrow biopsy of Chronic Myeloid Leukemia showing hypercellularity and expansion of immature granulocytic paratrabecular cuff
Bone marrow biopsy of Chronic Myeloid Leukemia showing hypercellularity and expansion of immature granulocytic paratrabecular cuff
Contributed by Rina Eden, DO

Contributed by Shabir Bhimji, MD

(Click Image to Enlarge)
Simplified hematopoiesis
Simplified hematopoiesis
Contributed By A. Rad and M. Häggström. (CC-BY-SA 3.0 license https://creativecommons.org/licenses/by-sa/3.0/deed.en_US)
Article Details

Article Author

Adithya Chennamadhavuni

Article Author

Varun Lyengar

Article Editor:

Alex Shimanovsky

Updated:

5/4/2022 1:45:14 PM

PubMed Link:

Leukemia

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