If a patient is resistant to either cladribine or pentostatin, then second-line therapy is pursued.

Monoclonal antibodies The most common treatment for cladribine-resistant disease is infusing monoclonal antibodies that destroy cancerous B cells. Rituximab is by far the most commonly used. Most patients receive one IV infusion over several hours each week for four to eight weeks. A 2003 publication found two partial and ten complete responses out of 15 patients with relapsed disease, for a total of 80% responding. The median patient (including non-responders) did not require further treatment for more than three years. This eight-dose study had a higher response rate than a four-dose study at Scripps, which achieved only 25% response rate. Rituximab has successfully induced a complete response in Hairy Cell-Variant.

Rituximab's major side effect is serum sickness, commonly described as an "allergic reaction", which can be severe, especially on the first infusion. Serum sickness is primarily caused by the antibodies clumping during infusion and triggering the complement cascade. Although most patients find that side effects are adequately controlled by anti-allergy drugs, some severe, and even fatal, reactions have occurred. Consequently, the first dose is always given in a hospital setting, although subsequent infusions may be given in a physician's office. Remissions are usually shorter than with the preferred first-line drugs, but hematologic remissions of several years' duration are not uncommon.

Other B cell-destroying monoclonal antibodies such as Alemtuzumab, Ibritumomab tiuxetan and I-131 Tositumomab may be considered for refractory cases.

Interferon-alpha Interferon-alpha is an immune system hormone that is very helpful to a relatively small number of patients, and somewhat helpful to most patients. In about 65% of patients, the drug helps stabilize the disease or produce a slow, minor improvement for a partial response.

The typical dosing schedule injects at least 3 million units of Interferon-alpha (not pegylated versions) three times a week, although the original protocol began with six months of daily injections.

Some patients tolerate IFN-alpha very well after the first couple of weeks, while others find that its characteristic flu-like symptoms persist. About 10% of patients develop a level of depression. It is possible that, by maintaining a steadier level of the hormone in the body, that daily injections might cause fewer side effects in selected patients. Drinking at least two liters of water each day, while avoiding caffeine and alcohol, can reduce many of the side effects.

A drop in blood counts is usually seen during the first one to two months of treatment. Most patients find that their blood counts get worse for a few weeks immediately after starting treatment, although some patients find their blood counts begin to improve within just two weeks.

It typically takes six months to figure out whether this therapy is useful. Common criteria for treatment success include:

- normalization of hemoglobin levels (above 12.0 g/dL),

- a normal or somewhat low platelet count (above 100 K/µL), and

- a normal or somewhat low absolute neutrophil count (above 1.5 K/µL).

If it is well tolerated, patients usually take the hormone for 12 to 18 months. An attempt may be made then to end the treatment, but most patients discover that they need to continue taking the drug for it to be successful. These patients often continue taking this drug indefinitely, until either the disease becomes resistant to this hormone, or the body produces an immune system response that limits the drug's ability to function. A few patients are able to achieve a sustained clinical remission after taking this drug for six months to one year. This may be more likely when IFN-alpha has been initiated shortly after another therapy. Interferon-alpha is considered the drug of choice for pregnant women with active HCL, although it carries some risks, such as the potential for decreased blood flow to the placenta.

Interferon-alpha works by sensitizing the hairy cells to the killing effect of the immune system hormone TNF-alpha, whose production it promotes. IFN-alpha works best on classic hairy cells that are not protectively adhered to vitronectin or fibronectin, which suggests that patients who encounter less fibrous tissue in their bone marrow biopsies may be more likely to respond to Interferon-alpha therapy. It also explains why non-adhered hairy cells, such as those in the bloodstream, disappear during IFN-alpha treatment well before reductions are seen in adhered hairy cells, such as those in the bone marrow and spleen.

Several treatments are available, and successful control of the disease is common.

Not everyone needs treatment immediately. Treatment is usually given when the symptoms of the disease interfere with the patient's everyday life, or when white blood cell or platelet counts decline to dangerously low levels, such as an absolute neutrophil count below one thousand cells per microliter (1.0 K/uL). Not all patients need treatment immediately upon diagnosis.

Treatment delays are less important than in solid tumors. Unlike most cancers, treatment success does not depend on treating the disease at an early stage. Because delays do not affect treatment success, there are no standards for how quickly a patient should receive treatment. However, waiting too long can cause its own problems, such as an infection that might have been avoided by proper treatment to restore immune system function. Also, having a higher number of hairy cells at the time of treatment can make certain side effects somewhat worse, as some side effects are primarily caused by the body's natural response to the dying hairy cells. This can result in the hospitalization of a patient whose treatment would otherwise be carried out entirely at the hematologist's office.

Single-drug treatment is typical. Unlike most cancers, only one drug is normally given to a patient at a time. While monotherapy is normal, combination therapy—typically using one first-line therapy and one second-line therapy—is being studied in current clinical trials and is used more frequently for refractory cases. Combining rituximab with cladribine or pentostatin may or may not produce any practical benefit to the patient. Combination therapy is almost never used with a new patient. Because the success rates with purine analog monotherapy are already so high, the additional benefit from immediate treatment with a second drug in a treatment-naïve patient is assumed to be very low. For example, one round of either cladribine or pentostatin gives the median first-time patient a decade-long remission; the addition of rituximab, which gives the median patient only three or four years, might provide no additional value for this easily treated patient. In a more difficult case, however, the benefit from the first drug may be substantially reduced and therefore a combination may provide some benefit.

Regular administration of exogenous granulocyte colony-stimulating factor (filgrastim) clinically improves neutrophil counts and immune function and is the mainstay of therapy, although this may increase risk for myelofibrosis and acute myeloid leukemia in the long term.

Over 90% of SCN responds to treatment with granulocyte colony-stimulating factor (filgrastim), which has significantly improved survival.

Certain medications can alter the number and function of white blood cells.

Medications that can cause leukopenia include clozapine, an antipsychotic medication with a rare adverse effect leading to the total absence of all granulocytes (neutrophils, basophils, eosinophils). The antidepressant and smoking addiction treatment drug bupropion HCl (Wellbutrin) can also cause leukopenia with long-term use. Minocycline, a commonly prescribed antibiotic, is another drug known to cause leukopenia. There are also reports of leukopenia caused by divalproex sodium or valproic acid (Depakote), a drug used for epilepsy (seizures), mania (with bipolar disorder) and migraine.

The anticonvulsant drug, lamotrigine, has been associated with a decrease in white blood cell count.

The FDA monograph for metronidazole states that this medication can also cause leukopenia, and the prescriber information suggests a complete blood count, including differential cell count, before and after, in particular, high-dose therapy.

Immunosuppressive drugs, such as sirolimus, mycophenolate mofetil, tacrolimus, ciclosporin, leflunomide and TNF inhibitors, have leukopenia as a known complication. Interferons used to treat multiple sclerosis, such as interferon beta-1a and interferon beta-1b, can also cause leukopenia.

Chemotherapy targets cells that grow rapidly, such as tumors, but can also affect white blood cells, because they are characterized by bone marrow as rapid growing. A common side effect of cancer treatment is neutropenia, the lowering of neutrophils (a specific type of white blood cell).

Decreased white blood cell count may be present in cases of arsenic toxicity.

The most successful treatment for angiosarcoma is amputation of the affected limb if possible. Chemotherapy may be administered if there is metastatic disease. If there is no evidence of metastasis beyond the lymphedematous limb, adjuvant chemotherapy may be given anyway due to the possibility of micrometastatic disease. Evidence supporting the effectiveness of chemotherapy is, in many cases, unclear due to a wide variety of prognostic factors and small sample size. However, there is some evidence to suggest that drugs such as paclitaxel, doxorubicin, ifosfamide, and gemcitabine exhibit antitumor activity.

There is as yet inadeqaute data from randomised controlled trials.

Treatment with HAART and ACE inhibitors/Angiotensin receptor blockers has been shown to be beneficial and should be given to all patients unless otherwise contra-indicated. General renoprotective measures and the treatment of the complications of nephrotic syndrome and kidney failure are adjunctive.

Corticosteroid treatment can be useful in patients who do not respond to the above treatment. There is some evidence that ciclosporin might be helpful in selective cases, however further trials are required on both steroids and ciclosporin before these drugs can become standardised treatment if at all.

Low white cell count may be due to acute viral infections, such as a cold or influenza. It has been associated with chemotherapy, radiation therapy, myelofibrosis, aplastic anemia (failure of white cell, red cell and platelet production), stem cell transplant, bone marrow transplant, HIV, AIDS, and steroid use.

Other causes of low white blood cell count include systemic lupus erythematosus, Hodgkin's lymphoma, some types of cancer, typhoid, malaria, tuberculosis, dengue, rickettsial infections, enlargement of the spleen, folate deficiencies, psittacosis, sepsis, Sjögren's syndrome and Lyme disease. It has also been shown to be caused by deficiency in certain minerals, such as copper and zinc.

Pseudoleukopenia can develop upon the onset of infection. The leukocytes (predominately neutrophils, responding to injury first) start migrating toward the site of infection, where they can be scanned. Their migration causes bone marrow to produce more WBCs to combat infection as well as to restore the leukocytes in circulation, but as the blood sample is taken upon the onset of infection, it contains low amount of WBCs, which is why it is termed "pseudoleukopenia".

A naïve T cell (T0 cell) is a T cell that has differentiated in bone marrow, and successfully undergone the positive and negative processes of central selection in the thymus. Among these are the naïve forms of helper T cells (CD4+) and cytotoxic T cells (CD8+). A naïve T cell is considered mature and, unlike activated or memory T cells, has not encountered its cognate antigen within the periphery.

There is no known cure for Ehlers–Danlos syndrome. Treatment is palliative. Close monitoring of the cardiovascular system, physiotherapy, occupational therapy, and orthopedic instruments (e.g., wheelchairs, bracing, casting) may be helpful. This can help with stabilizing the joints and prevent injury. Orthopedic instruments are helpful for the prevention of further joint damage, especially for long distances, although it is advised that individuals not become entirely dependent on them until there are no other options for mobility. One should avoid activities that cause the joint to lock or overextend.

A physician may prescribe casting to stabilize joints. Physicians may refer a patient to an orthotist for orthotic treatment (bracing). Physicians may also consult a physical and/or occupational therapist to help strengthen muscles and to teach people how to properly use and preserve their joints.

There are different types of physiotherapy. Aquatic therapy promotes muscular development and coordination. With manual therapy, the joint will be gently mobilized within the range of motion and/or manipulations.

If conservative therapy is not helpful, surgical repair of joints may be necessary. Medication to decrease pain or manage cardiac, digestive, or other related conditions may be prescribed. To decrease bruising and improve wound healing, some patients have responded to ascorbic acid (vitamin C). Special precautions are often taken by medical care workers because of the sheer amount of complications that tend to arise in EDS patients. In Vascular EDS, signs of chest or abdominal pain are to be considered trauma situations.

In general, medical intervention is limited to symptomatic therapy. Before pregnancy, patients with EDS should have genetic counseling and familiarize themselves with the risks to their own bodies that pregnancy poses. Children with EDS should be provided with information about the disorder so they can understand why contact sports and other physically stressful activities should be avoided. Children should be taught early on that demonstrating the unusual positions they can maintain due to loose joints should not be done as this may cause early degeneration of the joints. Patients may find it hard to cope with the drawbacks of the disease. In this case, emotional support and behavioral and psychological therapy can be useful. Support groups can be immensely helpful for patients dealing with major lifestyle changes and poor health. Family members, teachers, and friends should be informed about EDS so they can accept and assist the child.

Treatment depends on the thickness of the invasive component of the lentigo maligna. Treatment is essentially identical to other melanomas of the same thickness and stage.

Kostmann syndrome is a group of diseases that affect myelopoiesis, causing a congenital form of neutropenia (severe congenital neutropenia [SCN]), usually without other physical malformations. SCN manifests in infancy with life-threatening bacterial infections.

Most cases of SCN respond to treatment with granulocyte colony-stimulating factor (filgrastim), which increases the neutrophil count and decreases the severity and frequency of infections. Although this treatment has significantly improved survival, people with SCN are at risk of long-term complications such as hematopoietic clonal disorders (myelodysplastic syndrome, acute myeloid leukemia).

Kostmann disease (SCN3), the initial subtype recognized, was clinically described in 1956. This type has an autosomal recessive inheritance pattern, whereas the most common subtype of Kostmann syndrome, SCN1, shows autosomal dominant inheritance.

They are benign lesions and malignant degeneration is rare. They are usually treated with curettage which however have a high recurrence rate of 25%. As such if an en-bloc resection is possible this is advisable

Monocytes are a type of "leukocyte", or white blood cell. They are the largest type of leukocyte and can differentiate into macrophages and myeloid lineage dendritic cells. As a part of the vertebrate innate immune system monocytes also influence the process of adaptive immunity. There are at least three subclasses of monocytes in human blood based on their phenotypic receptors.

The instability of joints, leading to (sub)luxations and joint pain, often require surgical intervention in patients with Ehlers–Danlos syndrome. Instability of almost all joints can happen but appear most often in the lower and upper extremities, with the wrist, fingers, shoulder, knee, hip, and ankle being most common.

Common surgical procedures are joint debridement, tendon replacements, capsulorraphy, and arthroplasty. Studies have shown that after surgery, degree of stabilization, pain reduction, and patient satisfaction can improve, but surgery does not guarantee an optimal result: Patients and surgeons report being dissatisfied with the results. Consensus is that conservative treatment is more effective than surgery, particularly since patients have extra risks of surgical complications due to the disease. Three basic surgical problems arise due to EDS: the strength of the tissues is decreased, which makes the tissue less suitable for surgery; the fragility of the blood vessels can cause problems during surgery; and wound healing is often delayed or incomplete. If considering surgical intervention, it would be prudent to seek care from a surgeon with extensive knowledge and experience in treating patients with EDS and joint hypermobility issues.

Studies have shown that local anesthetics, arterial catheters and central venous catheters cause a higher risk in haematoma formation in patients with Ehlers–Danlos syndrome. Ehlers–Danlos syndrome patients also show a resistance to local anaesthetics. Resistance to Xylocaine and Bupivacaine is not uncommon, and Carbocaine tends to work better in EDS patents. Special recommendations for anesthesia in EDS patients are prepared by orphananesthesia and deal with all aspects of anesthesia for people with EDS. Detailed recommendations for anesthesia and perioperative care of patients with EDS should be used to improve patient safety.

Surgery with Ehlers–Danlos patients requires careful tissue handling and a longer immobilization afterward.

Low-protein food is recommended for this disorder, which requires food products low in particular types of amino acids (e.g., methionine).

Unlike classical seminoma, spermatocytic seminomas rarely metastasise, so radical orchidectomy alone is sufficient treatment, and retroperitoneal lymph node dissection and adjuvant chemotherapy or radiotherapy are generally not required.

No specific cure has been discovered for homocystinuria; however, many people are treated using high doses of vitamin B (also known as pyridoxine). Slightly less than 50% respond to this treatment and need to take supplemental vitamin B for the rest of their lives. Those who do not respond require a Low-sulfur diet (especially monitoring methionine), and most will need treatment with trimethylglycine. A normal dose of folic acid supplement and occasionally adding cysteine to the diet can be helpful, as glutathione is synthesized from cysteine (so adding cysteine can be important to reduce oxidative stress).

Betaine (N,N,N-trimethylglycine) is used to reduce concentrations of homocysteine by promoting the conversion of homocysteine back to methionine, i.e., increasing flux through the re-methylation pathway independent of folate derivatives (which is mainly active in the liver and in the kidneys).The re-formed methionine is then gradually removed by incorporation into body protein. The methionine that is not converted into protein is converted to S-adenosyl-methionine which goes on to form homocysteine again. Betaine is, therefore, only effective if the quantity of methionine to be removed is small. Hence treatment includes both betaine and a diet low in methionine. In classical homocystinuria (CBS, or cystathione beta synthase deficiency), the plasma methionine level usually increases above the normal range of 30 micromoles/L and the concentrations should be monitored as potentially toxic levels (more than 400 micromoles/L) may be reached.

In 2015 the first consensus guidelines for the diagnosis and treatment of chordoma were published in the Lancet Oncology.

In one study, the 10-year tumor free survival rate for sacral chordoma was 46%. Chondroid chordomas appear to have a more indolent clinical course.

In most cases, complete surgical resection followed by radiation therapy offers the best chance of long-term control. Incomplete resection of the primary tumor makes controlling the disease more difficult and increases the odds of recurrence. The decision whether complete or incomplete surgery should be performed primarily depends on the anatomical location of the tumor and its proximity to vital parts of the central nervous system.

Chordomas are relatively radioresistant, requiring high doses of radiation to be controlled. The proximity of chordomas to vital neurological structures such as the brain stem and nerves limits the dose of radiation that can safely be delivered. Therefore, highly focused radiation such as proton therapy and carbon ion therapy are more effective than conventional x-ray radiation.

There are no drugs currently approved to treat chordoma, however a clinical trial conducted in Italy using the PDGFR inhibitor Imatinib demonstrated a modest response in some chordoma patients. The same group in Italy found that the combination of imatinib and sirolimus caused a response in several patients whose tumors progressed on imatinib alone.

Initial treatments for minor erythrasma can begin with keeping the area clean and dry and with antibacterial soaps. The next level would be treated with topical fusidic acid, miconazole cream, and antibacterial solution such as clindamycin HCL to eradicate the bacteria. For aggressive types of Erythrasma, oral antibiotics like macrolides(erythromycin or azithromycin)can be prescribed. Below is a figure showing the different types and subtypes of therapies.

There is no current agreement on the most optimal treatment for this disease. There are plenty of limitations on these treatments such as more irritation, possible allergic reactions, and ulcerations. These treatments are suitable for most ages, but for young children it should be monitored very closely. Erythrasma if treated and found early on, is not fatal and the patient will live a full life. In more severe cases, it can be an indicator for another disease such as diabetes.

Monocytosis is the state of excess monocytes in the peripheral blood. It may be indicative of various disease states.

Examples of processes that can increase a monocyte count include:

- chronic inflammation

- stress response

- Cushing's syndrome (hyperadrenocorticism)

- immune-mediated disease

- granulomatous disease

- atherosclerosis

- necrosis

- red blood cell regeneration

- viral fever

- sarcoidosis

A high count of CD14+CD16++ monocytes is found in severe infection (sepsis)

In the field of atherosclerosis high numbers of the CD14++CD16+ intermediate monocytes were shown to be predictive of cardiovascular events in at risk populations.

Fungal pneumonia can be treated with antifungal drugs and sometimes by surgical debridement.

Gamma delta T cells (γδ T cells) are T cells that have a distinctive T-cell receptor (TCR) on their surface. Most T cells are αβ (alpha beta) T cells with TCR composed of two glycoprotein chains called α (alpha) and β (beta) TCR chains. In contrast, gamma delta (γδ) T cells have a TCR that is made up of one γ (gamma) chain and one δ (delta) chain. This group of T cells is usually much less common than αβ T cells, but are at their highest abundance in the gut mucosa, within a population of lymphocytes known as intraepithelial lymphocytes (IELs).

The antigenic molecules that activate gamma delta T cells are still largely unknown. However, γδ T cells are peculiar in that they do not seem to require antigen processing and major-histocompatibility-complex (MHC) presentation of peptide epitopes, although some recognize MHC class Ib molecules. Furthermore, γδ T cells are believed to have a prominent role in recognition of lipid antigens. They are of an invariant nature and may be triggered by alarm signals, such as heat shock proteins (HSP).

There also exists a γδ-T-cell sub-population within the epidermal compartment of the skin of mice. Originally referred to as Thy-1+ dendritic epidermal cells (Thy1+DEC), these cells are more commonly known as dendritic epidermal T cells (DETC). DETCs arise during fetal development and express an invariant and canonical Vγ3 Vδ1 T-cell receptor [using Garman nomenclature].

Naïve T cells are commonly characterized by the surface expression of L-selectin (CD62L); the absence of the activation markers CD25, CD44 or CD69; and the absence of memory CD45RO isoform. They also express functional IL-7 receptors, consisting of subunits IL-7 receptor-α, CD127, and common-γ chain, CD132. In the naïve state, T cells are thought to be quiescent and non-dividing, requiring the common-gamma chain cytokines IL-7 and IL-15 for homeostatic survival mechanisms.

It is not lethal in nature and is responsive to tetracycline or ciprofloxacin. Surgical treatment include rhinoplasty. However, if left untreated the disease can lead to sepsis, bleeding, or other chronic conditions that can be fatal.

In type II hypersensitivity (also tissue-specific, or cytotoxic hypersensitivity) the antibodies produced by the immune response bind to antigens on the patient's own cell surfaces. The antigens recognized in this way may either be intrinsic ("self" antigen, innately part of the patient's cells) or extrinsic (adsorbed onto the cells during exposure to some foreign antigen, possibly as part of infection with a pathogen). These cells are recognized by macrophages or dendritic cells, which act as antigen-presenting cells. This causes a B cell response, wherein antibodies are produced against the foreign antigen.

An example of type II hypersensitivity is the ABO blood incompatibility where the red blood cells have different antigens, causing them to be recognized as different; B cell proliferation will take place and antibodies to the foreign blood type are produced. IgG and IgM antibodies bind to these antigens to form complexes that activate the classical pathway of complement activation to eliminate cells presenting foreign antigens. That is, mediators of acute inflammation are generated at the site and membrane attack complexes cause cell lysis and death. The reaction takes hours to a day.

Type II reactions can affect healthy cells. Examples include red blood cells in autoimmune hemolytic anemia and acetylcholine receptors in myasthenia gravis.

Another example of type II hypersensitivity reaction is Goodpasture's syndrome where the basement membrane (containing collagen type IV) in the lung and kidney is attacked by one's own antibodies.

Another form of type II hypersensitivity is called antibody-dependent cell-mediated cytotoxicity (ADCC). Here, cells exhibiting the foreign antigen are tagged with antibodies (IgG or IgM). These tagged cells are then recognised by natural killer cells (NK) and macrophages (recognised via IgG bound (via the Fc region) to the effector cell surface receptor, CD16 (FcγRIII)), which in turn kill these tagged cells.