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.

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 bone marrow of patients with RCC contains islands of erythroid precursors and spare granulocytes. In some scenarios, multiple bone marrow biopsy examinations may be recommended before a diagnosis can be established.

The International Prognostic Scoring System (IPSS) was developed in the mid-1990s to assess the prognosis of MDS patients. This system stratifies cases into 2 groups; a lower-risk group (sub divided into low and intermediate-1) and a higher risk (subdivided into intermediate-2 and high). It uses the blast percentage, number of cytopaenias and bone marrow cytogenetics data to place cases of CMML into these groups. Due to the scoring system being developed for MDS, the more myeloproliferative cases of CMML (WBC >13x10) are excluded from the scoring system. Although the IPSS scoring system is used clinically, there is a high variability in each group. For this reason, new modalities for assessing prognosis in MDS (and CMML) are being developed.

The WHO has proposed a criterion for diagnosis and classification of MDS that may apply to most cases. However, occasional cases are difficult to classify into defined categories because of one or more unusual features:

- Rare cases with less than 5% blast will present with Auer rods. These cases usually have the features of RAMD.

- Occasionally, cases of MDS present with isolated neutropenia or thrombocytopenia without anemia and with dysplastic changes confined to the single lineage. The term refractory neutropenia and refractory thrombocytopenia have sometimes been used to describe these cases. A diagnosis of MDS in patients with neutropenia or thrombocytopenia without anemia should be made with caution.

- Patients with RA or RAEB occasionally present with leukocytosis or thrombocytosis instead of the usual cytopenia.

Symptoms result from underproduction of red blood cells (weakness, pallor, failure to thrive, pica), white blood cells (recurrent or overwhelming infection), and/or platelets (bleeding).

Bone marrow transplant is the only known curative treatment.

The blood count typically shows decreased numbers of blood cells—including a decreased amount of circulating red blood cells, white blood cells, and platelets.

The bone marrow may show hemophagocytosis.

The liver function tests are usually elevated. A low level of the protein albumin in the blood is common.

The serum C reactive protein, erythrocyte sedimentation rate, and ferritin level are markedly elevated. In children, a ferritin above 10000 is very sensitive and specific for the diagnosis of HLH, however, the diagnostic utility for ferritin is less for adult HLH patients.

The serum fibrinogen level is usually low and the D-dimer level is elevated.

The sphingomyelinase is elevated.

Bone marrow biopsy shows histiocytosis.

The current (2008) diagnostic criteria for HLH are

1. A molecular diagnosis consistent with HLH. These include the identification of pathologic mutations of PRF1, UNC13D, or STX11.

OR

2. Fulfillment of five out of the eight criteria below:

- Fever (defined as a temperature >100.4 °F, >38 °C)

- Enlargement of the spleen

- Decreased blood cell counts affecting at least two of three lineages in the peripheral blood:

- Haemoglobin <9 g/100 ml (in infants <4 weeks: haemoglobin <10 g/100 ml) (anemia)

- Platelets <100×10/L (thrombocytopenia)

- Neutrophils <1×10/L (neutropenia

- High blood levels of triglycerides (fasting, greater than or equal to 265 mg/100 ml) and/or decreased amounts of fibrinogen in the blood (≤ 150 mg/100 ml)

- Ferritin ≥ 500 ng/ml

- Haemophagocytosis in the bone marrow, spleen or lymph nodes

- Low or absent natural killer cell activity

- Soluble CD25 (soluble IL-2 receptor) >2400 U/ml (or per local reference laboratory)

In addition, in the case of familial HLH, no evidence of malignancy should be apparent.

It should be noted that not all five out of eight criteria are required for diagnosis of HLH in adults, and a high index of suspicion is required for diagnosis as delays results in increased mortality. The diagnostic criteria were developed in pediatric populations and have not been validated for adult HLH patients. Attempts to improve diagnosis of HLH have included use of the HScore, which can be used to estimate an individual's risk of HLH.

If the splenomegaly underlies hypersplenism, a splenectomy is indicated and will correct the hypersplenism. However, the underlying cause of the hypersplenism will most likely remain; consequently, a thorough diagnostic workup is still indicated, as, leukemia, lymphoma and other serious disorders can cause hypersplenism and splenomegaly. After splenectomy, however, patients have an increased risk for infectious diseases.

Patients undergoing splenectomy should be vaccinated against "Haemophilus influenzae", "Streptococcus pneumoniae", and "Meningococcus". They should also receive annual influenza vaccinations. Long-term prophylactic antibiotics may be given in certain cases.

In cases of infectious mononucleosis splenomegaly is a common symptom and health care providers may consider using abdominal ultrasonography to get insight into a person's condition. However, because spleen size varies greatly, ultrasonography is not a valid technique for assessing spleen enlargement and should not be used in typical circumstances or to make routine decisions about fitness for playing sports.

Ringed sideroblasts are seen in the bone marrow.

The anemia is moderate to severe and dimorphic. Microscopic viewing of the red blood cells will reveal marked unequal cell size and abnormal cell shape. Basophilic stippling is marked and target cells are common. Pappenheimer bodies are present in the red blood cells. The mean cell volume is commonly decreased (i.e., a microcytic anemia), but MCV may also be normal or even high. The RDW is increased with the red blood cell histogram shifted to the left. Leukocytes and platelets are normal. Bone marrow shows erythroid hyperplasia with a maturation arrest.

In excess of 40% of the developing erythrocytes are ringed sideroblasts. Serum iron, percentage saturation and ferritin are increased. The total iron-binding capacity of the cells is normal to decreased. Stainable marrow hemosiderin is increased.

Sideroblastic anemias are often described as responsive or non-responsive in terms of increased hemoglobin levels to pharmacological doses of vitamin B.

1- Congenital: 80% are responsive, though the anemia does not completely resolve.

2- Acquired clonal: 40% are responsive, but the response may be minimal.

3- Acquired reversible: 60% are responsive, but course depends on treatment of the underlying cause.

Severe refractory sideroblastic anemias requiring regular transfusions and/or that undergo leukemic transformation (5-10%) significantly reduce life expectancy.

Anti-platelet autoantibodies in a pregnant woman with ITP will attack the patient's own platelets and will also cross the placenta and react against fetal platelets. Therefore, ITP is a significant cause of fetal and neonatal immune thrombocytopenia. Approximately 10% of newborns affected by ITP will have platelet counts <50,000/uL and 1% to 2% will have a risk of intracerebral hemorrhage comparable to infants with neonatal alloimmune thrombocytopenia (NAIT).

No lab test can reliably predict if neonatal thrombocytopenia will occur. The risk of neonatal thrombocytopenia is increased with:

- Mothers with a history of splenectomy for ITP

- Mothers who had a previous infant affected with ITP

- Gestational (maternal) platelet count less than 100,000/uL

It is recommended that pregnant women with thrombocytopenia or a previous diagnosis of ITP should be tested for serum antiplatelet antibodies. A woman with symptomatic thrombocytopenia and an identifiable antiplatelet antibody should be started on therapy for their ITP which may include steroids or IVIG. Fetal blood analysis to determine the platelet count is not generally performed as ITP-induced thrombocytopenia in the fetus is generally less severe than NAIT. Platelet transfusions may be performed in newborns, depending on the degree of thrombocytopenia. It is recommended that neonates be followed with serial platelet counts for the first few days after birth.,

Refractory anemia with ring sideroblasts (RARS) is a type of myelodysplastic syndrome. RARS is characterized by 5% or less myeloblasts in bone marrow. RARS is distinguished from refractory anemia by having 15% or more ringed sideroblasts among the erythroid precursors in the bone marrow.

Symptoms may include abdominal pain, chest pain, chest pain similar to pleuritic pain when stomach, bladder or bowels are full, back pain, early satiety due to splenic encroachment, or the symptoms of anemia due to accompanying cytopenia.

Signs of splenomegaly may include a palpable left upper quadrant abdominal mass or splenic rub. It can be detected on physical examination by using Castell's sign, Traube's space percussion or Nixon's sign, but an ultrasound can be used to confirm diagnosis. In patients where the likelihood of splenomegaly is high, the physical exam is not sufficiently sensitive to detect it; abdominal imaging is indicated in such patients.

Refractory anemia with excess of blasts (RAEB) is a type of myelodysplastic syndrome with a marrow blast percentage of 5% to 19%.

In MeSH, "Smoldering leukemia" is classified under RAEB.

Pralatrexate is one compound currently under investigations for the treatment of PTCL.

In adults, particularly those living in areas with a high prevalence of "Helicobacter pylori" (which normally inhabits the stomach wall and has been associated with peptic ulcers), identification and treatment of this infection has been shown to improve platelet counts in a third of patients. In a fifth, the platelet count normalized completely; this response rate is similar to that found in treatment with rituximab, which is more expensive and less safe. In children, this approach is not supported by evidence, except in high prevalence areas. Urea breath testing and stool antigen testing perform better than serology-based tests; moreover, serology may be false-positive after treatment with IVIG.

The old diagnostic criteria for the illness included: Chronic non-malignant lymphoproliferation, elevated peripheral blood DNTs and defective in vitro Fas mediated apoptosis.

The new criteria require chronic non-malignant lymphoproliferation (over six months lymphadenopathy and/or splenomegaly), elevated peripheral blood DNTs. A primary accessory in diagnosis is defective in vitro Fas mediated apoptosis and somatic or germline mutation in ALPS causative gene (FAS, FASL, CASP10).

The secondary accessory in diagnosis are elevated biomarkers (plasma sFASL over 200 pg/ml, plasma IL-10 >20 pg/ml, plasma or serum vitamin B12 >1500 ng/L, Plasma IL-18 >500pg/ml) and immunohistochemical findings on biopsy consistent with ALPS as determined by an experienced hematopathologist. Another sign is autoimmune cytopenias and polyclonal hypergammaglobulinemia and a family history of ALPS or non-malignant lymphoproliferation.

A definitive diagnosis is chronic non-malignant lymphoproliferation and/or elevated peripheral blood DNTs plus one primary accessory criterion. A probable diagnosis is the same but with one secondary accessory criterion.

Leukemic cells are invariably present in samples of peripheral blood to a variable extent. Pancytopenia (anemia, neutropenia, thrombocytopenia) is commonly seen as well.

The diagnosis is made upon blood tests to confirm not only hemolytic anemia and immune thrombocytopenic purpura, but also a positive direct antiglobulin test (DAT) and an absence of any known underlying cause.

Other antibodies may occur directed against neutrophils and lymphocytes, and "immunopancytopenia" has been suggested as a better term for this syndrome.

Erythroid dysplasia is a condition in which immature red blood cells (erythroid cells) in the bone marrow are abnormal in size, shape, organization, and/or number. Erythroid dysplasia may be caused by vitamin deficiency or chemotherapy, or it may be a sign of refractory anemia, which is a myelodysplastic syndrome. Also called erythrodysplasia.

Treatment with conventional immunochemotherapy is usually indicated; in younger patients, allogeneic bone marrow transplantation may be curative.

2003 nomenclature

- IA - Fas

- IB - Fas ligand

- IIA - Caspase 10

- IIB - Caspase 8

- III - unknown

- IV - Neuroblastoma RAS viral oncogene homolog

Revised nomenclature (2010)

- ALPS-FAS: Fas. Germline FAS mutations. 70% of patients. Autosomal dominant. Dominant negative and haploinsufficient mutations described.

- ALPS-sFAS: Fas. Somatic FAS mutations in DNT compartment. 10% of patients

- ALPS-FASL: Fas ligand. Germline FASL mutations. 3 reported cases

- ALPS-CASP10: Caspase 10. Germline CASP10 mutation. 2% of patients

- ALPS-U: Undefined. 20% of patients

- CEDS: Caspase 8 deficiency state. No longer considered a subtype of ALPS but distinct disorder

- RALD: NRAS, KRAS. Somatic mutations in NRAS and KRAS in lympocyte compartment. No longer considered a subtype of ALPS but distinct disesase

Cytopenia is a reduction in the number of mature blood cells. It takes a number of forms:

- Low red blood cell count: resulting in anemia.

- Low white blood cell count: leukopenia or neutropenia. Because neutrophils make up at least half of all white cells, they are almost always low in leukopenia .

- Low platelet count: thrombocytopenia.

- Low granulocyte count: granulocytopenia

- Low red blood cell, white blood cell, and platelet counts: pancytopenia.

Refractory cytopenia with multilineage dysplasia is a form of myelodysplastic syndrome.

It is abbreviated "RCMD".