Information about Leukemia

Leukemia
Classification & external resources

A Wright's stained bone marrow aspirate smear of patient with precursor B-cell acute lymphoblastic leukemia.
ICD-10	C91.-C95.
ICD-9	208.9
ICD-O:	9800-9940
DiseasesDB	7431
MeSH	D007938

Leukemia or leukaemia (Greek leukos, “white”; haima, “blood”) (see spelling differences) is a cancer of the blood or bone marrow and is characterized by an abnormal proliferation (production by multiplication) of blood cells, usually white blood cells (leukocytes). It is part of the broad group of diseases called hematological neoplasms.

Symptoms

Damage to the bone marrow, by way of displacing the normal bone marrow cells with higher numbers of immature white blood cells, results in a lack of blood platelets, which are important in the blood clotting process. This means people with leukemia may become bruised, bleed excessively, or develop pinprick bleeds (petechiae).

White blood cells, which are involved in fighting pathogens, may be suppressed or dysfunctional. This could cause the patient's immune system (white blood cells etc.) to start attacking other body cells.

Finally, the red blood cell deficiency leads to anemia, which may cause dyspnea. All symptoms can be attributed to other diseases; for diagnosis, blood tests and a bone marrow examination are required.

Some other related symptoms

• Fever, chills, night sweats and other flu-like symptoms
• Weakness and fatigue
• Loss of appetite and/or weight
• Swollen or bleeding gums
• Excess bleeding (from a minor cut)
• Neurological symptoms (headache)
• Enlarged liver and spleen
• Easy bruising
• Frequent infection
• Bone pain
• Joint pain
• Dizziness
• Swollen tonsils

The word leukemia, which means 'white blood,' is derived from the disease's namesake high white blood cell counts that most leukemia patients have before treatment. The high number of white blood cells are apparent when a blood sample is viewed under a microscope. Frequently, these extra white blood cells are immature or dysfunctional. The excessive number of cells can also interfere with the normal function of other cells.

Some leukemia patients do not have high white blood cell counts visible during a regular blood count. This less-common condition is called aleukemia. The bone marrow still contains cancerous white blood cells which disrupt the normal production of blood cells. However, the leukemic cells are staying in the marrow instead of entering the bloodstream, where they would be visible in a blood test. For an aleukemic patient, the white blood cell counts in the bloodstream can be normal or low. Aleukemia can occur in any of the four major types of leukemia, and is particularly common in hairy cell leukemia.

Four major types

Leukemia is a broad term covering a spectrum of diseases.

Leukemia is clinically and pathologically split into its acute and chronic forms.

• Acute leukemia is characterized by the rapid proliferation of immature blood cells. This crowding makes the bone marrow unable to produce healthy blood cells. Acute forms of leukemia can occur in children and young adults. (In fact, it is a more common cause of death for children in the US than any other type of malignant disease). Immediate treatment is required in acute leukemias due to the rapid progression and accumulation of the malignant cells, which then spill over into the bloodstream and spread to other organs of the body. However, CNS involvement is uncommon, though the disease occasionally causes cranial nerve palsies.
• Chronic leukemia is distinguished by the excessive build up of relatively mature, but still abnormal, blood cells. Typically taking months to years to progress, the cells are produced at a much higher rate than normal cells, resulting in many abnormal white blood cells in the blood. Chronic leukemia mostly occurs in older people, but can theoretically occur in any age group. Whereas acute leukemia must be treated immediately, chronic forms are sometimes monitored for some time before treatment to ensure maximum effectiveness of therapy.

Furthermore, the diseases are classified into lymphocytic or lymphoblastic which indicate that the cancerous change took place in a type of marrow cell that normally goes on to form lymphocytes, and myelogenous or myeloid which indicate that the cancerous change took place in a type of marrow cell that normally goes on to form red cells, some types of white cells, and platelets (see lymphoid cells vs. myeloid cells).

Combining these two classifications provides a total of four main categories:

	Acute	Chronic
lymphocytic leukemia	Acute lymphocytic leukemia (also known as Acute Lymphoblastic Leukemia, or ALL) is the most common type of leukemia in young children. This disease also affects adults, especially those age 65 and older.	Chronic lymphocytic leukemia (CLL) most often affects adults over the age of 55. It sometimes occurs in younger adults, but it almost never affects children.
myelogenous leukemia (or "myeloid")	Acute myelogenous leukemia (also known as Acute Myeloid Leukemia, or AML) occurs more commonly in adults than in children. This type of leukemia was previously called "acute nonlymphocytic leukemia".	Chronic myelogenous leukemia (CML) occurs mainly in adults. A very small number of children also develop this disease.

Within these main categories, there are typically several subcategories.

Causes and risk factors

There is no single known cause for all of the different types of leukemia. The different leukemias likely have different causes, and very little is certain about what causes them. Researchers have strong suspicions about four possible causes:

• natural or artificial ionizing radiation
• certain kinds of chemicals
• some viruses
• genetic predispositions

Leukemia, like other cancers, result from somatic mutations in the DNA which activate oncogenes or deactivate tumor suppressor genes, and disrupt the regulation of cell death, differentiation or division. These mutations may occur spontaneously or as a result of exposure to radiation or carcinogenic substances and are likely to be influenced by genetic factors. Cohort and case-control studies have linked exposure to petrochemicals, such as benzene, and hair dyes to the development of some forms of leukemia.

Viruses have also been linked to some forms of leukemia. For example, certain cases of ALL are associated with viral infections by either the human immunodeficiency virus (HIV, responsible for AIDS) or human T-lymphotropic virus (HTLV-1 and -2, causing adult T-cell leukemia/lymphoma).

Fanconi anemia is also a risk factor for developing acute myelogenous leukemia.

Until the cause or causes of leukemia are found, there is no way to prevent the disease. Even when the causes become known, they may prove to be things which are not readily controllable, such as naturally occurring background radiation, and therefore not especially helpful for prevention purposes.

Treatment options for leukemia by type

Acute Myelogenous Leukemia (AML)

It is most common for adults; more men than women are affected. Many different chemotherapeutic plans are available for the treatment of AML. Overall, the strategy is to control bone marrow and systemic (whole-body) disease while offering specific treatment for the central nervous system (CNS), if involved. In general, most oncologists rely on combinations of drugs for the initial, induction phase of chemotherapy. Such combination chemotherapy usually offers the benefits of early remission (lessening of the disease) and a lower risk of disease resistance. Consolidation or "maintenance" treatments may be given to prevent disease recurrence once remission has been achieved. Consolidation treatment often entails a repetition of induction chemotherapy or the intensification chemotherapy with added drugs. By contrast, maintenance treatment involves drug doses that are lower than those administered during the induction phase.

In addition, specific treatment plans may be used, depending on the type of leukemia that has been diagnosed. Whatever the plan, it is important for the patient to understand the treatment that is being given and the decision-making process behind the choice.

Initial treatment of AML

Initial treatment of AML usually begins with induction chemotherapy using a combination of drugs such as daunorubicin (DNR), cytarabine (ara-C), idarubicin, thioguanine, etoposide, or mitoxantrone, anabolic steroids.

Follow-up treatment

Follow-up therapy for such patients may involve:

• supportive care, such as intravenous nutrition and treatment with oral antibiotics (e.g., ofloxacin, rifampin), especially in patients who have prolonged granulocytopenia; that is too few mature granulocytes (neutrophils), the bacteria-destroying white blood cells that contain small particles, or granules (< 100 granulocytes per cubic millimeter for 2 weeks)
• injection with colony-stimulating factors such as granulocyte colony-stimulating factor (G-CSF), which may help to shorten the period of granulocytopenia that results from induction therapy
• transfusions with red blood cells and platelets

Patients with newly diagnosed disease also may be considered for stem cell transplantation (SCT), either from the bone marrow or other sources. Allogeneic bone marrow transplant (alloBMT) is reserved primarily for patients under 55 years of age who have a compatible family donor. Approximately half of newly diagnosed AML patients are in this age group, with 75% achieving a complete remission (CR) after induction and consolidation therapy. Allogeneic bone marrow transplant is available for about 15% of all patients with AML. Unfortunately, it is estimated that only 7% of all AML patients will be cured using this procedure.

People who receive stem cell transplantation (SCT, alloBMT) require protective isolation in the hospital, including filtered air, sterile food, and sterilization of the microorganisms in the gut, until their total white blood cell (WBC) count is above 500.

Treatment of central nervous system leukemia, if present, may involve injection of chemotherapeutic drugs (e.g., cytarabine or ara-C, methotrexate) into the areas around the brain and spinal cord.

Consolidation or maintenance therapy

Once the patient is in remission, he or she will receive consolidation or maintenance therapy, for example, consolidation therapy with high-dose ara-C (HDAC) with/without anthracycline drugs).

If, however, the AML patient has resistant disease (about 15%) or relapses (about 70%), second remissions sometimes are achieved by treating them with:

• conventional induction chemotherapy
• high-dose ara-C (HDAC), with/without other drugs
• etoposide or other single chemotherapeutic agents

Elderly AML patients have special treatment concerns. They may be less able to tolerate the septicemia (blood poisoning) associated with granulocytopenia, and they often have higher rates of myelodysplastic ('preleukemia') syndrome (MDS). Individuals who are over age 75 or who have significant medical conditions can be treated effectively with low-dose ara-C. High-dose post-induction chemotherapy is unlikely to be tolerated by elderly patients.

Until recently, the treatment plans and responses of children with AML did not differ much from those of adults. Yet new, more intensive induction and consolidation treatments have resulted in higher remission rates and prolonged survivals. Many induction trials have produced good results using combinations of cytarabine (ara-C) plus an anthracycline (e.g., daunorubicin, doxorubicin). In children under 3 years of age, the anthracycline used for induction should be chosen with care, since doxorubicin produces more toxicity and related deaths than daunorubicin.

Consolidation therapy is complex, but it should include at least two courses of high-dose ara-C (HDAC). Children who have hyperleukocytosis (too many white blood cells), especially monocytic M5 leukemia, have a poor prognosis.

Chronic Myelogenous Leukemia (CML)

The challenge of treating newly diagnosed CML is to determine the best overall strategy to control the disease. General strategies for management include a variety of options:

Leukapheresis, also known as a peripheral blood stem cell transplant, with stem cell cryopreservation (frozen storage) prior to any other treatment. The patient's blood is passed through a machine that removes the stem cells and then returns the blood to the patient. Leukapheresis usually takes 3 or 4 hours to complete. The stem cells may or may not be treated with drugs to kill any cancer cells. The stem cells then are stored until they are transplanted back into the patient.

HLA (human leukocyte antigen) typing of all patients under age 60, as well as typing of siblings, parents, and children, if available. This procedure will determine whether a compatible donor is available for stem cell transplantation.

Pre-treatment fertility measures (e.g., cryopreservation of semen prior to treatment; completion of a pregnancy prior to treatment) in young patients who have not completed their families.

Interferon-alpha (INF-a) therapy'.

Chemotherapy with drugs such as hydroxyurea (Hydrea®), busulfan (Myleran®) or imatinib mesylate (Gleevec(tm)).

In general, CML treatment options are divided into two groups: those that do not increase survival and those that do. Chemotherapeutic drugs such as hydroxyurea (Hydrea®) and busulfan (Myleran®) can normalize the blood count for a period of time, but they do not increase survival. They often are used to control blood counts in patients who cannot undergo SCT or who do not respond to interferon therapy because of age or medical considerations.

Gleevec, is one of a new class of cancer drugs that disables an abnormal enzyme in the cancerous cell, kills it, but leaves healthy cells virtually untouched. Other cancer therapies, such as chemotherapy, attack healthy cells as well as cancer cells, leaving patients with unpleasant and often severe side effects.

In June of 2006, the Food and Drug Administration (FDA) approved the oral tyrosine kinase inhibitor dasatinib (Sprycel(tm)) to treat CML that does not respond to other therapy.

One treatment that does impact on CML survival is allogeneic bone marrow transplantation, the use of high dose chemotherapy and radiation followed by infusion of a donor bone marrow. This procedure removes the chromosomal abnormality in a large percentage of patients and for them is curative. In addition, there is treatment with interferon (INF). About 20% to 30% of patients taking interferon show elimination of the abnormal chromosome and improved survival. Recent findings also suggest that low-dose cytarabine (ara-C), in combination with interferon, may be more beneficial than interferon alone. For patients who do not respond to interferon, autologous or allogeneic stem cell transplantation is the only alternative.

Patients with advanced-phase disease may be treated with cytotoxic drugs. For example, individuals showing myeloid transformation may be given drugs that are used to induce remission in AML - that is, daunorubicin and cytarabine, with or without 6-thioguanine or etoposide. Blast cell numbers will be reduced temporarily, but they will increase again within 3 to 6 weeks. Individuals showing lymphoid transformation have a slightly better outlook. They are treated with drugs used in the management of acute lymphocytic leukemia (ALL) - that is, prednisone, vincristine, and daunorubicin, with or without L-asparaginase.

New drugs that are being studied in clinical trials of CML include homoherringtonine with interferon-alpha (INF-a), paclitaxel (Taxol®), QS21 (a plant extract that heightens immune responses), and amifostin (a chemical that lessens some side effects of chemotherapy). In addition, clinical trials are evaluating the potential benefits of substances such as vaccines, monoclonal antibodies (immunologic substances that can direct the patient's immune system to kill cancer cells), and hormones (e.g., growth factors, interleukins).

Acute Lymphocytic Leukemia (ALL)

Proper management of ALL focuses on control of bone marrow and systemic (whole-body) disease as well as prevention of cancer at other sites, particularly the central nervous system (CNS). In general, ALL treatment is divided into several phases:

Induction chemotherapy to bring about remission - that is, leukemic cells are no longer found in bone marrow samples. For adult ALL, standard induction plans include prednisone, vincristine, and an anthracycline drug; other drug plans may include L-asparaginase or cyclophosphamide. For children with low-risk ALL, standard therapy usually consists of three drugs (prednisone, L-asparaginase, and vincristine) for the first month of treatment. High-risk children may receive these drugs plus an anthracycline such as daunorubicin.

Consolidation therapy (1-3 months in adults; 4-8 months in children) to eliminate any leukemia cells that are still "hiding" within the body. A combination of chemotherapeutic drugs is used to keep the remaining leukemia cells from developing resistance. Patients with low- to average-risk ALL receive therapy with antimetabolite drugs such as methotrexate and 6-mercaptopurine (6-MP). High-risk patients receive higher drug doses plus treatment with extra chemotherapeutic agents.

CNS prophylaxis (preventive therapy) to stop the cancer from spreading to the brain and nervous system. Standard prophylaxis may consist of:

1. Cranial (head) irradiation plus spinal tap or intrathecal (IT) delivery (into the space around the spinal cord and brain) of the drug methotrexate.
2. High-dose systemic and IT methotrexate, without cranial irradiation
3. IT chemotherapy.

Only children with T-cell leukemia, a high white blood cell count, or leukemia cells in the cerebrospinal fluid (CSF) need to receive cranial irradiation as well as IT therapy.

Maintenance treatments with chemotherapeutic drugs (e.g., prednisone + vincristine + cyclophosphamide + doxorubicin; methotrexate + 6-MP) to prevent disease recurrence once remission has been achieved. Maintenance therapy usually involves drug doses that are lower than those administered during the induction phase. In children, an intensive 6-month treatment program is needed after induction, followed by 2 years of maintenance chemotherapy.

Follow-up therapy for ALL patients usually consists of:

• supportive care, such as intravenous nutrition and treatment with oral antibiotics (e.g., ofloxacin, rifampin), especially in patients with prolonged granulocytopenia; that is, too few mature granulocytes (neutrophils), the bacteria-destroying white blood cells that contain small particles, or granules (< 100 granulocytes per cubic millimeter for 2 weeks)
• transfusions with red blood cells and platelets

A laboratory test known as polymerase chain reaction (PCR) is advisable for ALL patients, since it may help to identify specific genetic abnormalities. Such abnormalities have a large impact upon prognosis and, consequently, treatment plans. PCR testing is especially important for patients whose disease is B-cell in type. B-cell ALL usually is not cured by standard ALL therapy. Instead, higher response rates are achieved with the aggressive, cyclophosphamide-based regimens that are used for non-Hodgkin's lymphoma.

Among ALL patients, 3-5% children and 25-50% of adults are positive for the Philadelphia chromosome (Ph1). Because these patients have a worse prognosis than other individuals with ALL, many oncologists recommend allogeneic bone marrow transplantation (alloBMT), since remission may be brief following conventional ALL chemotherapy.

People who receive bone marrow transplantation will require protective isolation in the hospital, including filtered air, sterile food, and sterilization of the microorganisms in the gut, until their total white blood cell (WBC) count is above 500.

Recurrent ALL patients usually do not benefit from additional chemotherapy alone. If possible, they should receive re-induction chemotherapy, followed by allogeneic bone marrow transplant (alloBMT).

Alternatively, patients with recurrent ALL may benefit from participation in new clinical trials of alloBMT, immune system agents, and chemotherapeutic agents, or low-dose radiotherapy, if the cancer recurs throughout the body or CNS.

Chronic Lymphocytic Leukemia (CLL)

CLL is probably incurable by present treatments. But, fortunately, a large group of CLL patients do not require therapy. Studies suggest that people with Stage A CLL (that is, individuals who have fewer than three areas of enlarged lymphoid tissue) do not benefit from early treatment. They may, in fact, suffer drawbacks because of it. Therefore, most oncologists base CLL treatment upon both the stage and symptoms of the patient.

For example, in older patients (60+ years) who have low-risk early stage disease (Rai Stage 0) a conservative "watch and wait" approach may be taken.

By contrast, older individuals with CLL-related complications or more advanced disease (Rai Stage III or IV) may benefit from chemotherapy and treatment with a corticosteroid (e.g., prednisone, prednisolone).

Corticosteroids are first-line agents for people in whom the immune systems has been altered by CLL. CLL may cause autoimmune syndromes in which the patient's immune system attacks and destroys his or her own blood cells. When the red blood cells are affected, the condition is known as immunohemolytic anemia, characterized by decreased numbers of red blood cells, which may cause fatigue, dizziness, and shortness of breath. When the blood platelets are affected, it is called immune-mediated thrombocytopenia, in which a decreased numbers of platelets may lead to bleeding.

For younger patients who are experiencing symptoms, the physician may consider early chemotherapy, plus allogeneic or autologous bone marrow transplantation (alloBMT; autoBMT).

In general, the indications for treatment are:

• falling hemoglobin or platelet count
• progression to a later stage of disease
• painful, disease-related overgrowth of lymph nodes or spleen
• lymphocyte doubling time (an indicator of lymphocyte reproduction) of fewer than 12 months

Transformation of CLL to high-grade disease or aggressive non-Hodgkin's lymphoma

If the patient experiences blood flow problems caused by high numbers of leukemia cells in the circulation, the physician may recommend leukapheresis, also known as apheresis, to separate out white blood cells, prior to chemotherapy. Symptoms that are related to enlargement of the lymph nodes in one area or an overgrown spleen may be treated by localized, low-dose radiotherapy, or surgical management by splenectomy (removal of the spleen). But if leukemia has invaded the lymph nodes at many different sites, total body irradiation (TBI) may be needed.

Chemotherapy for CLL

The chemotherapeutic plans that are used most often for CLL are:

• combination chemotherapy with chlorambucil (Leukeran®) or cyclophosphamide (Cytoxan®) plus a corticosteroid drug such as prednisone, or
• single-agent treatments with nucleoside drugs such as fludarabine, pentostatin, or cladribine (2-chlorodeoxyadenisine; 2-CDA). However, such drugs usually are reserved for cases in which CLL is resistant (unresponsive to treatment) or returns after chemotherapy with chlorambucil or cyclophosphamide.

People with intermediate (Rai Stage I and II) or advanced (Rai Stage III or IV) disease may be helped by participation in a clinical trial. At the present time, clinical trials are being conducted using immunologic compounds (e.g., interferons, monoclonal antibodies) as well as new chemotherapeutic agents (e.g., bryostatin, dolastatin 10, and PSC 83 - a cyclosporine drug given with chemotherapy to overcome drug resistance).

Hairy Cell Leukemia (HCL)

Hairy cell leukemia is an incurable, indolent blood disorder in which mutated, partly matured B cells accumulate in the bone marrow. Its name is derived from the shape of the cells, which look like they are covered with short, fine, hair-shaped projections. Unlike any other leukemia, HCL is characterized by low white blood cell counts.

Patients with hairy cell leukemia who are symptom-free typically do not receive immediate treatment. They engage in "watchful waiting" with routine bloodwork and exams every three to six months to monitor disease progression and identify any new symptoms.

Treatment is generally considered necessary when the patient shows signs and symptoms such as low blood cell counts (e.g., infection-fighting neutrophil count below 1.0 K/ul), frequent infections, unexplained bruises, anemia, or fatigue that is significant enough to disrupt the patient's everyday life.

Patients who need treatment, which includes most newly diagnosed HCL cases, usually receive either cladribine or pentostatin, which are both in a class of chemotherapeutic drugs known as purine analogs or nucleosides. In most cases, one round of treatment will produce a prolonged remission.

Other treatments include rituximab infusion or self-injection with Interferon-alpha. In limited cases, the patient may benefit from splenectomy (removal of the spleen). These treatments are not typically given as the first treatment for a new patient because their success rates are lower than cladribine or pentostatin.

In the short term, especially when neutrophil counts are low, an immune system hormone called granulocyte colony-stimulating factor may be taken to increase white blood cell counts. This is believed to help prevent or treat an infection. Many patients also take antibiotics until their white blood cell counts have recovered to normal levels.

Research

Significant research into the causes, diagnosis, treatment, and prognosis of leukemia is being done. Hundreds of clinical trials are being planned or conducted at any given time. Studies may focus on effective means of treatment, better ways of treating the disease, improving the quality of life for patients, or appropriate care in remission or after cure.

External links

Patient support and disease-related fundraising

• Leukemia CARE -- UK's leading charity for leukemia patients
• Leukemia and Lymphoma Society -- US's leading charity for leukemia patients
• Leukemia Research Foundation -- Illinois (US) charity
• Leukaemia Research Fund UK's largest funder of leukaemia research. Provides patient information booklets.
• CHILDREN with LEUKAEMIA -- UK's leading charity dedicated to fighting childhood leukaemia

Research organizations

• Association of Cancer Online Resources (ACOR) Leukemia Links -- disseminates clinical research information
• The Therapeutic Advances in Childhood Leukemia (TACL) Consortium -- US research group

•  • [ e] Pathology: hematology (primarily /, /)
WBCs	hematological malignancy (Lymphoma, leukemia) -cytosis (Agranulocytosis, Leukocytosis, Lymphocytosis, Monocytosis) • -penia (Lymphopenia, Neutropenia)
RBCs/anemia/ hemoglobinopathy	nutritional anemia: Iron deficiency anemia, Plummer-Vinson syndrome, Megaloblastic anemia (Pernicious anemia) hereditary hemolytic anemia: G6PD Deficiency, Thalassemia, Sickle-cell disease/trait, Hereditary spherocytosis, Hereditary elliptocytosis, Hereditary stomatocytosis acquired hemolytic anemia: Warm autoimmune hemolytic anemia, HUS, MAHA, PNH aplastic anemia: Acquired PRCA, Diamond-Blackfan anemia, Fanconi anemia • Sideroblastic anemia • Hemochromatosis
Coagulation/platelets	coagulopathy: DIC • Hemophilia (A, B, C, XIII) • Von Willebrand disease Purpura: Henoch-Schnlein, ITP, TTP primary hypercoagulable state: Protein C deficiency - Protein S deficiency - Antithrombin III deficiency other hemorrhagic conditions: Bernard-Soulier syndrome - Glanzmann's thrombasthenia - Grey platelet syndrome
Histiocytosis	WHO-I Langerhans cell histiocytosis - non-Langerhans-cell histiocytosis/WHO-II (Juvenile xanthogranuloma, Hemophagocytic lymphohistiocytosis) - malignant histiocytic disorders/WHO-III (Acute monocytic leukemia, Malignant histiocytosis, Erdheim-Chester disease)
Other	Asplenia/hyposplenism - Methemoglobinemia

•  • [ e] Hematological malignancy histology (ICD-O 9590-9989)
Lymphomas (9590-9759)	Hodgkin's lymphoma vs. Non-Hodgkin lymphoma - Diffuse lymphoma vs. Follicular lymphoma B-cell lymphoma (Small cell, Primary effusion, Burkitt's, Splenic marginal zone, MALT) T-cell lymphoma (Cutaneous, Mycosis fungoides/Szary's disease, Angioimmunoblastic, Anaplastic large cell, Hepatosplenic) plasma cell (Plasmacytoma, Multiple myeloma) mast cell tumor (Mast-cell sarcoma, Malignant mastocytosis, Malignant histiocytosis, Langerhans cell histiocytosis)
Immunoproliferative disorders (9760-9799)	Waldenstrm macroglobulinemia - Lymphomatoid granulomatosis
Lymphoid leukemias (9800-9839)	ALL - CLL - T-cell leukemia (Adult, Large granular lymphocyte, Prolymphocytic, Acute lymphoblastic) - B-cell leukemia (Prolymphocytic)
Myeloid leukemias (9840-9939, 9963)	AML (M2, APL/M3, AMoL/M5, Erythroleukemia/M6) - CML (CMoL, CNL, Philadelphia chromosome) - Granulocytic sarcoma
Other leukemias (9940-9949)	Hairy cell leukemia - Aggressive NK-cell leukemia
Myeloproliferative disease (9950-9961)	Polycythemia vera - Essential thrombocytosis - Myelofibrosis
Other (9964-9989)	Hypereosinophilic syndrome - Post-transplant lymphoproliferative disorder - Myelodysplastic syndrome