The Düsseldorf score stratifies cases using four categories, giving one point for each; bone marrow blasts ≥5%, LDH >200U/L, haemoglobin ≤9g/dL and a platelet count ≤100,000/uL. A score of 0 indicates a low risk group' 1-2 indicates an intermediate risk group and 3-4 indicates a high risk group. The cumulative 2 year survival of scores 0, 1-2 and 3-4 is 91%, 52% and 9%; and risk of AML transformation is 0%, 19% and 54% respectively.

A new method developed using data from the M.D. Anderson Cancer Center found that a haemoglobin level of 2.5 x 10/L, >0% immature myeloid cells, >10% bone marrow blasts causes a reduced overall survival. This data allows cases of CMML to be stratified into low, intermediate-1, intermediate-2 and high risk groups. These groups have median survival times of 24, 15, 8 and 5 months respectively.

Although not yet formally incorporated in the generally accepted classification systems, molecular profiling of myelodysplastic syndrome genomes has increased the understanding of prognostic molecular factors for this disease. For example, in low-risk MDS, "IDH1" and "IDH2" mutations are associated with significantly worsened survival.

The majority (90%) of cases have not had detectable cytogenetic abnormalities. Most importantly, the Philadelphia chromosome and other BCR/ABL fusion genes are not detected.

Epidemiologically, the disorder usually develops slowly and is mainly observed in people over the age of 50. It may also develop as a side-effect of treatment with some drugs that target hematological disorders, such as polycythemia vera or chronic myelogenous leukemia.

Diagnosis of myelofibrosis is made on the basis of bone marrow biopsy. A physical exam of the abdomen may reveal enlargement of the spleen, the liver, or both.

Blood tests are also used in diagnosis. Primary myelofibrosis can begin with a blood picture similar to that found in polycythemia vera or chronic myelogenous leukemia. Most people with myelofibrosis have moderate to severe anemia. Eventually thrombocytopenia, a decrease of blood platelets develops. When viewed through a microscope, a blood smear will appear markedly abnormal, with presentation of pancytopenia, which is a reduction in the number of all blood cell types: red blood cells, white blood cells, and platelets. Red blood cells may show abnormalities including bizarre shapes, such as teardrop-shaped cells, and nucleated red blood cell precursors may appear in the blood smear. (Normally, mature red blood cells in adults do not have a cell nucleus, and the presence of nucleated red blood cells suggests that immature cells are being released into the bloodstream in response to a very high demand for the bone marrow to produce new red blood cells.) Immature white cells are also seen in blood samples, and basophil counts are increased.

When late in the disease progression an attempt is made to take a sample of bone marrow by aspiration, it may result in a dry tap, meaning that where the needle can normally suck out a sample of semi-liquid bone marrow, it produces no sample because the marrow has been replaced with collagen fibers. A bone marrow biopsy will reveal collagen fibrosis, replacing the marrow that would normally occupy the space.

Primary myelofibrosis (PMF) is associated with the "JAK2V617F" mutation in up to 50% of cases, the "JAK2" exon 12 mutations in 1-2% of cases, and the MPL (thrombopoietin receptor) mutation in up to 5% of cases:

- Prefibrotic/cellular phase - increased, small and atypical megakaryocytes which cluster, reticulin fibrosis, later trichrome (collagenous) fibrosis, and increased myeloid precursors

- Fibrotic phase - collagenous fibrosis with lack of marrow elements

Depending on the nature of the myeloproliferative neoplasm, diagnostic tests may include red cell mass determination (for polycythemia), bone marrow aspirate and trephine biopsy, arterial oxygen saturation and carboxyhaemoglobin level, neutrophil alkaline phosphatase level, vitamin B (or B binding capacity), serum urate or direct sequencing of the patient's DNA.

According to the WHO Classification of Hematopoietic and Lymphoid Neoplasms 2008 myeloproliferative neoplasms are divided into categories by diagnostic characteristics as follows:

The outlook in MDS is variable, with about 30% of patients progressing to refractory AML. The median survival rate varies from years to months, depending on type. Stem-cell transplantation offers possible cure, with survival rates of 50% at 3 years, although older patients do poorly.

Indicators of a good prognosis:

Younger age; normal or moderately reduced neutrophil or platelet counts; low blast counts in the bone marrow (< 20%) and no blasts in the blood; no Auer rods; ringed sideroblasts; normal or mixed karyotypes without complex chromosome abnormalities; and "in vitro" marrow culture with a nonleukemic growth pattern

Indicators of a poor prognosis:

Advanced age; severe neutropenia or thrombocytopenia; high blast count in the bone marrow (20-29%) or blasts in the blood;

Auer rods; absence of ringed sideroblasts; abnormal localization or immature granulocyte precursors in bone marrow section;

completely or mostly abnormal karyotypes, or complex marrow chromosome abnormalities and "in vitro" bone marrow culture with a leukemic growth pattern

Karyotype prognostic factors:

- Good: normal, -Y, del(5q), del(20q)

- Intermediate or variable: +8, other single or double anomalies

- Poor: complex (>3 chromosomal aberrations); chromosome 7 anomalies

The IPSS is the most commonly used tool in MDS to predict long-term outcome.

Cytogenetic abnormalities can be detected by conventional cytogenetics, a FISH panel for MDS, or virtual karyotype.

Diagnosis is confirmed histologically by tissue biopsy. Hematoxylin-eosin stain of biopsy slide will show features of Langerhans Cell e.g. distinct cell margin, pink granular cytoplasm. Presence of Birbeck granules on electron microscopy and immuno-cytochemical features e. g. CD1 positivity are more specific. Initially routine blood tests e.g. full blood count, liver function test, U&Es, bone profile are done to determine disease extent and rule out other causes. Radiology will show osteolytic bone lesions and damage to the lung. The latter may be evident in chest X-rays with micronodular and interstitial infiltrate in the mid and lower zone of lung, with sparing of the Costophrenic angle or honeycomb appearance in older lesions. MRI and CT may show infiltration in sella turcica. Assessment of endocrine function and bonemarrow biopsy are also performed when indicated.

- S-100 protein is expressed in a cytoplasmic pattern

- peanut agglutinin (PNA) is expressed on the cell surface and perinuclearly

- major histocompatibility (MHC) class II is expressed (because histiocytes are macrophages)

- CD1a

- langerin (CD207), a Langerhans Cell–restricted protein that induces the formation of Birbeck granules and is constitutively associated with them, is a highly specific marker.

The first test for diagnosis myelophthisis involves looking at a small sample of blood under a microscope. Myelophthisis is suggested by the presence of red blood cells that contain nuclei or are teardrop-shaped (dacryocytes), or immature granulocyte precursor cells which indicates leukoerythroblastosis is occurring because the displaced hematopoietic cells begin to undergo extramedullary hematopoiesis. These immature granulocytes are seen in peripheral blood smears. Diagnosis is confirmed when a bone marrow biopsy demonstrates significant replacement of the normal bone marrow compartment by fibrosis, malignancy or other infiltrative process. The presence of immature blood cell precursors helps distinguish another cause of pancytopenia, aplastic anemia, from myelophthisic anemia because in aplastic anemia the hematopoietic cells are damaged and immature blood cells are not seen in the peripheral blood.

There may be evidence of extramedullary hematopoiesis (marrow elements can be found in the spleen, liver).

There are two internationally accepted treatment protocols, which are geographically based:

- North America: the Children’s Oncology Group (COG) JMML study

- Europe: the European Working Group for Myelodysplastic Syndromes (EWOG-MDS) JMML study

The following procedures are used in one or both of the current clinical approaches listed above:

Evidence is conflicting on the prognostic significance of chloromas in patients with acute myeloid leukemia. In general, they are felt to augur a poorer prognosis, with a poorer response to treatment and worse survival; however, others have reported chloromas associate, as a biologic marker, with other poor prognostic factors, and therefore do not have independent prognostic significance.

No distinct immunophenotype abnormality for CNL has been described.

See OHSU 2013 findings of gene CSF3R, mutation p. T6181

The following criteria are required in order to diagnose JMML:

All 3 of the following:

- No Philadelphia chromosome or BCR/ABL fusion gene.

- Peripheral blood monocytosis >1 x 10/L.

- Less than 20% blasts (including promonocytes) in the blood and bone marrow (blast count is less than 2% on average)

Two or more of the following criteria:

- Hemoglobin F increased for age.

- Immature granulocytes and nucleated red cells in the peripheral blood.

- White blood cell count >10 x 10/L.

- Clonal chromosomal abnormality (e.g., monosomy 7).

- Granulocyte macrophage colony-stimulating factor (GM-CSF) hypersensitivity of myeloid progenitors in vitro.

These criteria are identified through blood tests and bone marrow tests.

Blood tests: A complete blood count (CBC) will be performed on a child suspected of having JMML and throughout the treatment and recovery of a child diagnosed with JMML.

The differential diagnosis list includes infectious diseases like Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, histoplasma, mycobacteria, and toxoplasma, which can produce similar symptoms.

Definitive diagnosis of a chloroma usually requires a biopsy of the lesion in question. Historically, even with a tissue biopsy, pathologic misdiagnosis was an important problem, particularly in patients without a clear pre-existing diagnosis of acute myeloid leukemia to guide the pathologist. In one published series on chloroma, the authors stated that 47% of the patients were initially misdiagnosed, most often as having a malignant lymphoma.

However, with advances in diagnostic techniques, the diagnosis of chloromas can be made more reliable. Traweek et al. described the use of a commercially available panel of monoclonal antibodies, against myeloperoxidase, CD68, CD43, and CD20, to accurately diagnose chloroma via immunohistochemistry and differentiate it from lymphoma. Nowadays, immunohistochemical staining using monoclonal antibodies against CD33 and CD117 would be the mainstay of diagnosis. The increasingly refined use of flow cytometry has also facilitated more accurate diagnosis of these lesions.

Historically, hematological malignancies have been most commonly divided by whether the malignancy is mainly located in the blood (leukemia) or in lymph nodes (lymphomas).

However, the influential WHO Classification (published in 2001) placed a greater emphasis on cell lineage.

Relative proportions of hematological malignancies in the United States

The following revised diagnostic criteria for essential thrombocythaemia were proposed in 2005. The diagnosis requires the presence of both A criteria together with B3 to B6, or of criterion A1 together with B1 to B6. The criteria are as follows:

- A1. Platelet count > 450 × 10/µL for at least 2 months.

- A2. Acquired V617F JAK2 mutation present

- B1. No cause for a reactive thrombocytosis

- normal inflammatory indices

- B2. No evidence of iron deficiency

- stainable iron in the bone marrow or normal red cell mean corpuscular volume

- B3. No evidence of polycythemia vera

- hematocrit < midpoint of normal range or normal red cell mass in presence of normal iron stores

- B4. No evidence of chronic myeloid leukemia

- But the Philadelphia chromosome may be present in up to 10% of cases. Patients with the Philadelphia chromosome have a potential for the development of acute leukemia, especially acute lymphocytic leukemia.

- B5. No evidence of myelofibrosis

- no collagen fibrosis and ≤ grade 2 reticulin fibrosis (using 0–4 scale)

- B6. No evidence of a myelodysplastic syndrome

- no significant dysplasia

- no cytogenetic abnormalities suggestive of myelodysplasia

Hydroxycarbamide and anagrelide are contraindicated during pregnancy and nursing. Essential thrombocytosis can be linked with a three-fold increase in risk of miscarriage. Throughout pregnancy, close monitoring of the mother and fetus is recommended. Low-dose low molecular weight heparin (e.g. enoxaparin) may be used. For life-threatening complications, the platelet count can be reduced rapidly using platelet apheresis, a procedure that removes platelets from the blood and returns the remainder to the patient.

For the analysis of a suspected "hematological malignancy", a complete blood count and blood film are essential, as malignant cells can show in characteristic ways on light microscopy. When there is lymphadenopathy, a biopsy from a lymph node is generally undertaken surgically. In general, a bone marrow biopsy is part of the "work up" for the analysis of these diseases. All specimens are examined microscopically to determine the nature of the malignancy. A number of these diseases can now be classified by cytogenetics (AML, CML) or immunophenotyping (lymphoma, myeloma, CLL) of the malignant cells.

The first clue to a diagnosis of AML is typically an abnormal result on a complete blood count. While an excess of abnormal white blood cells (leukocytosis) is a common finding with the leukemia, and leukemic blasts are sometimes seen, AML can also present with isolated decreases in platelets, red blood cells, or even with a low white blood cell count (leukopenia). While a presumptive diagnosis of AML can be made by examination of the peripheral blood smear when there are circulating leukemic blasts, a definitive diagnosis usually requires an adequate bone marrow aspiration and biopsy as well as ruling out pernicious anemia (Vitamin B12 deficiency), folic acid deficiency and copper deficiency.

Marrow or blood is examined under light microscopy, as well as flow cytometry, to diagnose the presence of leukemia, to differentiate AML from other types of leukemia (e.g. acute lymphoblastic leukemia - ALL), and to classify the subtype of disease. A sample of marrow or blood is typically also tested for chromosomal abnormalities by routine cytogenetics or fluorescent "in situ" hybridization. Genetic studies may also be performed to look for specific mutations in genes such as "FLT3", nucleophosmin, and "KIT", which may influence the outcome of the disease.

Cytochemical stains on blood and bone marrow smears are helpful in the distinction of AML from ALL, and in subclassification of AML. The combination of a myeloperoxidase or Sudan black stain and a nonspecific esterase stain will provide the desired information in most cases. The myeloperoxidase or Sudan black reactions are most useful in establishing the identity of AML and distinguishing it from ALL. The nonspecific esterase stain is used to identify a monocytic component in AMLs and to distinguish a poorly differentiated monoblastic leukemia from ALL.

The diagnosis and classification of AML can be challenging, and should be performed by a qualified hematopathologist or hematologist. In straightforward cases, the presence of certain morphologic features (such as Auer rods) or specific flow cytometry results can distinguish AML from other leukemias; however, in the absence of such features, diagnosis may be more difficult.

The two most commonly used classification schemata for AML are the older French-American-British (FAB) system and the newer World Health Organization (WHO) system. According to the widely used WHO criteria, the diagnosis of AML is established by demonstrating involvement of more than 20% of the blood and/or bone marrow by leukemic myeloblasts, except in the three best prognosis forms of acute myeloid leukemia with recurrent genetic abnormalities (t(8;21), inv(16), and t(15;17)) in which the presence of the genetic abnormality is diagnostic irrespective of blast percent. The French–American–British (FAB) classification is a bit more stringent, requiring a blast percentage of at least 30% in bone marrow (BM) or peripheral blood (PB) for the diagnosis of AML. AML must be carefully differentiated from "preleukemic" conditions such as myelodysplastic or myeloproliferative syndromes, which are treated differently.

Because acute promyelocytic leukemia (APL) has the highest curability and requires a unique form of treatment, it is important to quickly establish or exclude the diagnosis of this subtype of leukemia. Fluorescent "in situ" hybridization performed on blood or bone marrow is often used for this purpose, as it readily identifies the chromosomal translocation [t(15;17)(q22;q12);] that characterizes APL. There is also a need to molecularly detect the presence of PML/RARA fusion protein, which is an oncogenic product of that translocation.

The one known curative treatment is allogeneic stem cell transplantation, but this approach involves significant risks.

Other treatment options are largely supportive, and do not alter the course of the disorder (with the possible exception of ruxolitinib, as discussed below). These options may include regular folic acid, allopurinol or blood transfusions. Dexamethasone, alpha-interferon and hydroxyurea (also known as hydroxycarbamide) may play a role.

Lenalidomide and thalidomide may be used in its treatment, though peripheral neuropathy is a common troublesome side-effect.

Frequent blood transfusions may also be required. If the patient is diabetic and is taking a sulfonylurea, this should be stopped periodically to rule out drug-induced thrombocytopenia.

Splenectomy is sometimes considered as a treatment option for patients with myelofibrosis in whom massive splenomegaly is contributing to anaemia because of hypersplenism, particularly if they have a heavy requirement for blood transfusions. However, splenectomy in the presence of massive splenomegaly is a high-risk procedure, with a mortality risk as high as 3% in some studies.

In November 2011, the FDA approved ruxolitinib (Jakafi) as a treatment for intermediate or high-risk myelofibrosis. Ruxolitinib serves as an inhibitor of JAK 1 and 2.

The "New England Journal of Medicine" (NEJM) published results from two Phase III studies of ruxolitinib. These data showed that the treatment significantly reduced spleen volume, improved symptoms of myelofibrosis, and was associated with improved overall survival compared to placebo.

Acute erythroid leukemia is rare, accounting for only 3–5% of all acute myeloid leukemia cases. One study estimated an occurrence rate of 0.077 cases per 100,000 people each year. 64–70% of people with this condition are male, and most are elderly, with a median age of 65.

CML accounts for 8% of all leukaemias in the UK, and around 680 people were diagnosed with the disease in 2011.

Information on prognosis is limited by the rarity of the condition. Prognosis appears to be no different to AML in general, taking into account other risk factors. Acute erythroid leukemia (M6) has a relatively poor prognosis. A 2010 study of 124 patients found a median overall survival of 8 months. A 2009 study on 91 patients found a median overall survival for erythroleukemia patients of 36 weeks, with no statistically significant difference to other AML patients. AEL patients did have a significantly shorter disease free survival period, a median of 32 weeks, but this effect was explained by other prognostic factors. That is, AEL is often associated with other risk factors, like monosomal karyotypes and a history of myelodysplastic syndrome. Prognosis is worse in elderly patients, those with a history of myelodysplastic syndrome, and in patients who had previously received chemotherapy for the treatment of a different neoplasm.

Treatment of this disorder involves treatment of the underlying cancer.