The only known cure for CAEBV is allogenic haematopoietic stem cell transplant (HSCT), with all other treatment options (rituximab, cytotoxic chemotherapy and immunosuppressive therapy) being nothing more than stopgaps.

Treatment is most commonly directed at autoimmune disease and may be needed to treat bulky lymphoproliferation. First line therapies include corticosteroids (very active but toxic with chronic use), and IVIgG, which are not as effective as in other immune cytopenia syndromes.

Second line therapies include: mycophenolate mofetil (cellcept) which inactivates inosine monophosphate, most studied in clinical trials with responses varying (relapse, resolution, partial response). It does not affect lymphoproliferation or reduce DNTs, with no drug-drug interactions. This treatment is commonly used agent in patients who require chronic treatment based on tolerance and efficacy. It may cause hypogammaglobulinemia (transient) requiring IVIgG replacement.

Sirolimus (rapamycin, rapamune) which is a mTOR (mammalian target of rapamycin) inhibitor can be active in most patients and can in some cases lead to complete or near-complete resolution of autoimmune disease (>90%) With this treatment most patients have complete resolution of lymphoproliferation, including lymphadenopathy and splenomegaly (>90%) and have elimination of peripheral blood DNTs. Sirolimus may not be as immune suppressive in normal lymphocytes as other agents. Some patients have had improvement in immune function with transition from cellcept to rapamycin and it has not been reported to cause hypogammaglobulinemia. Hypothetically, Sirolimus may have lower risk of secondary cancers as opposed to other immune suppressants and requires therapeutic drug monitoring. It is the second most commonly used agent in patients that require chronic therapy. It is mostly well tolerated (though side effects include mucositis, diarrhea, hyperlipidemia, delayed wound healing) with drug-drug interactions. It has better activity against autoimmune disease and lymphoproliferation than mycophenolate mofetil and other drugs; however, sirolimus requires therapeutic drug monitoring and can cause mucositis. A risk with any agent in pre-cancerous syndrome as immune suppression can decreased tumor immunosurvellence. Its mTOR inhibitors active against lymphomas, especially EBV+ lymphomas. The Goal serum trough is 5-15 ng/ml and can consider PCP prophylaxis but usually not needed.

Other treatments may include drugs like Fansidar, mercaptopurine: More commonly used in Europe. Another is rituximab but this can cause lifelong hypogammaglobulinemia and a splenectomy but there is a >30% risk of pneumococcal sepsis even with vaccination and antibiotic prophylaxis

Treatment consists mainly of high dose antibiotics for active infections and prophylactic antibiotics for prevention of future infections. GM-CSF therapy or bone marrow transplant might be considered for severe cases. Prognosis is difficult to predict, but patients receiving treatment are generally able to survive to adulthood.

Treatment depends on the grade (I-III) but typically consist of cortisone, rituximab and chemotherapy (etoposide, vincristine, cyclophosphamide, doxorubicin). Methotrexate has been seen to induce LYG. Interferon alpha has been used by the US National Cancer Institute with varying results. In recent years hematopoietic stem cell transplantation has been performed on LYG-patients with relative good success; a 2013 study identifying 10 cases found that 8 patients survived the treatment and were disease free several years later. Two of the disease free patients later died, one from suicide and one from graft versus host disease after a second transplantation 4 years later. The remaining two patients died from sepsis after the transplantation.

Once a diagnosis is made, each individual's treatment is based on an individual’s clinical condition. Hematopoietic stem cell transplant is a possible treatment of this condition but its effectiveness is unproven.

Additionally, magnesium supplementation is a promising potential treatment for XMEN. One of the consequences of loss of "MAGT1" function is a decreased level of unbound intracellular Mg2+. This decrease leads to loss of expression of an immune cell receptor called "NKG2D", which is involved in EBV-immunity. Remarkably, Mg2+ supplementation can restore "NKG2D" expression and other functions that are abnormal in patients with XMEN. Early evidence suggests continuous oral magnesium threonate supplementation is safe and well tolerated. Nonetheless, further research is needed to evaluate the use of Mg2+ as a treatment for XMEN. It remains unclear if such supplementation will protect against the development of lymphoma in patients with XMEN. Investigators at the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health currently have clinical protocols to study new approaches to the diagnosis and treatment of this disorder.

PTLD may spontaneously regress on reduction or cessation of immunosuppressant medication, and can also be treated with addition of anti-viral therapy. In some cases it will progress to non-Hodgkin's lymphoma and may be fatal. A phase 2 study of adoptively transferred EBV-specific T cells demonstrated high efficacy with minimal toxicity.

Without HSCT the condition is inevitably fatal and even HSCT is no guarantee, with a significant portion of patients dying from the disease progression. Factors indicative of a poor prognosis include: thrombocytopenia, late onset of the disease (age ≥ 8 years) and T cell involvement.

There is no proven or standard first-line chemotherapy that works for the majority of AITL patients. There are several clinical trials that offer treatment options that can fight the disease. Stem cell transplantation is the treatment of choice, with the allogeneic one being the preference because AITL tends to recur after autologous transplants.

Surgical resection is usually ineffective because of the depth of the tumour. Treatment with irradiation and corticosteroids often only produces a partial response and tumour recurs in more than 90% of patients. Median survival is 10 to 18 months in immunocompetent patients, and less in those with AIDS. The addition of IV methotrexate and folinic acid (leucovorin) may extend survival to a median of 3.5 years. If radiation is added to methotrexate, median survival time may increase beyond 4 years. However, radiation is not recommended in conjunction with methotrexate because of an increased risk of leukoencephalopathy and dementia in patients older than 60. In AIDS patients, perhaps the most important factor with respect to treatment is the use of highly active anti-retroviral therapy (HAART), which affects the CD4+ lymphocyte population and the level of immunosuppression. The optimal treatment plan for patients with PCNSL has not been determined. Combination chemotherapy and radiotherapy at least doubles survival time, but causes dementia and leukoencephalopathy in at least 50% of patients who undergo it. The most studied chemotheraputic agent in PCNSL is methotrexate (a folate analogue that interferes with DNA repair). Methotrexate therapy in patients with PCNSL typically requires hospitalization for close monitoring and intravenous fluids. Leucovorin is often given for the duration of the therapy. Standard chemotherapeutic regimens for lymphoma such as CHOP are ineffective in PCNSL, probably due to poor penetration of the agents through the blood brain barrier.

Newer treatments, such as high dose chemotherapy combined with stem cell transplant are proving to increase survival by years.

A phase 1 clinical trial of ibrutinib - an inhibitor of Bruton's tyrosine kinase - in 13 patients reported responses in 10 (77%). Five of the responses were complete.

Physicians often prescribe the antibiotic trimethoprim-sulfamethoxazole to prevent bacterial infections. This drug also has the benefit of sparing the normal bacteria of the digestive tract. Fungal infection is commonly prevented with itraconazole, although a newer drug of the same type called voriconazole may be more effective. The use of this drug for this purpose is still under scientific investigation.

Interferon, in the form of interferon gamma-1b (Actimmune) is approved by the Food and Drug Administration for the prevention of infection in CGD. It has been shown to reduce infections in CGD patients by 70% and to decrease their severity. Although its exact mechanism is still not entirely understood, it has the ability to give CGD patients more immune function and therefore, greater ability to fight off infections. This therapy has been standard treatment for CGD for several years.

The initial response to radiotherapy is often excellent, and may result in a complete remission. However, the duration of response with radiotherapy alone remains short, with median survival after treatment with radiotherapy just 18 months. Methotrexate based chemotherapy markedly improves survival, with some studies showing median survival after methotrexate chemotherapy reaching 48 months.

It is generally resistant to cancer chemotherapy drugs that are active against other lymphomas, and carries a poor prognosis.

Sirolimus has been proposed as a treatment option.

The most common treatment for XLA is an intravenous infusion of immunoglobulin (IVIg, human IgG antibodies) every 3–4 weeks, for life. IVIg is a human product extracted and pooled from thousands of blood donations. IVIg does not cure XLA but increases the patient's lifespan and quality of life, by generating passive immunity, and boosting the immune system. With treatment, the number and severity of infections is reduced. With IVIg, XLA patients may live a relatively healthy life. A patient should attempt reaching a state where his IgG blood count exceeds 800 mg/kg. The dose is based on the patient's weight and IgG blood-count.

Muscle injections of immunoglobulin (IMIg) were common before IVIg was prevalent, but are less effective and much more painful; hence, IMIg is now uncommon.Subcutaneous treatment (SCIg) was recently approved by the U.S. Food and Drug Administration (FDA), which is recommended in cases of severe adverse reactions to the IVIg treatment.

Antibiotics are another common supplementary treatment. Local antibiotic treatment (drops, lotions) are preferred over systemic treatment (pills) for long-term treatment, if possible.One of the future prospects of XLA treatment is gene therapy, which could potentially cure XLA. Gene therapy technology is still in its infancy and may cause severe complications such as cancer and even death. Moreover, the long-term success and complications of this treatment are, as yet, unknown.

Once a diagnosis is made, the treatment is based on an individual’s clinical condition. Based on the apparent activation of the mTOR pathway, Lucas and colleagues treated patients with rapamycin, an mTOR inhibitor. This effectively reduced hepatosplenomegaly and lymphadenopathy, most likely by restoring the normal balance of naïve, effector, and memory cells in the patients’ immune system. More research is needed to determine the most effective timing and dosage of this medication and to investigate other treatment options. Investigators at the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health currently have clinical protocols to study new approaches to the diagnosis and treatment of this disorder.

The current mortality is over 60% after 5 years. However, due to hematopoietic stem cell transplantation being performed only in recent years, this number could potentially be lowered in the future. In patients with CNS involvement, treatment with Interferon alpha at US National Cancer Institute resulted in complete remission in 90% of patients.

Radiotherapy is a valid first option for "MALT lymphoma". It provides local control and potential cure in localized gastric stage IE and II 1E disease with 5-year EFS of 85-100% reported in retrospective studies. However, the irradiation field is potentially large as it must include the whole stomach, which can vary greatly in size and shape. Irradiation techniques have improved considerably in the last 20 years, including treating the patient in a fasting state, decreasing the irradiated field and required dose. The moderate dose of 30 Gray (Gy) of involved-field radiotherapy administered in 15 fractions (doses) can be associated with tolerable toxicity and excellent outcomes. Hence, radiotherapy is the preferred approach for local disease where antibiotic therapy has failed, or is not indicated. Evidence also suggests that radiotherapy can be utilized to control localized relapses outside the original radiation field.

Currently Aggressive NK-cell leukemia, being a subtype of PTCL, is treated similarly to B-cell lymphomas. However, in recent years, scientists have developed techniques to better recognize the different types of lymphomas, such as PTCL. It is now understood that PTCL behaves differently from B-cell lymphomas and therapies are being developed that specifically target these types of lymphoma. Currently, however, there are no therapies approved by the U.S. Food and Drug Administration (FDA) specifically for PTCL. Anthracycline-containing chemotherapy regimens are commonly offered as the initial therapy. Some patients may receive a stem cell transplant. Novel approaches to the treatment of PTCL in the relapsed or refractory setting are under investigation.

Antiviral treatment has been tried with some success in a small number of patients.

Paracetamol (acetaminophen) and NSAIDs, such as ibuprofen, may be used to reduce fever and pain. Prednisone, a corticosteroid, while used to try to reduce throat pain or enlarged tonsils, remains controversial due to the lack of evidence that it is effective and the potential for side effects. Intravenous corticosteroids, usually hydrocortisone or dexamethasone, are not recommended for routine use but may be useful if there is a risk of airway obstruction, a very low platelet count, or hemolytic anemia.

There is little evidence to support the use of antivirals such as aciclovir and valacyclovir although they may reduce initial viral shedding. Although antivirals are not recommended for people with simple infectious mononucleosis, they may be useful (in conjunction with steroids) in the management of severe EBV manifestations, such as EBV meningitis, peripheral neuritis, hepatitis, or hematologic complications.

Although antibiotics exert no antiviral action they may be indicated to treat bacterial secondary infections of the throat, such as with streptococcus (strep throat). However, ampicillin and amoxicillin are not recommended during acute Epstein–Barr virus infection as a diffuse rash may develop.

Treatment is not necessary since the lesion is benign, however the person may have esthetic concerns about the appearance. The condition often resolves rapidly with high dose acyclovir or desiclovir but recurs once this therapy is stopped, or as the underlying immunocompromise worsens. Topical use of podophyllum resin or retinoids has also been reported to produce temporary remission. Antiretroviral drugs such as zidovudine may be effective in producing a significant regression of OHL. Recurrence of the lesion may also signify that highly active antiretroviral therapy (HAART) is becoming ineffective.

PFAPA syndrome typically resolves spontaneously. Treatment options are used to lessen the severity of episodes. Treatment is either medical or surgical.

One treatment often used is a dose of a corticosteroid at the beginning of each fever episode. A single dose usually ends the fever within several hours. However, in some children, they can cause the fever episodes to occur more frequently. Interleukin-1 inhibition appears to be effective in treating this condition.

Surgical removal of the tonsils appears to be beneficial compared to no surgery in symptom resolution and number of future episodes. The evidence to support surgery is; however, of moderate quality.

Infectious mononucleosis is generally self-limiting, so only symptomatic or supportive treatments are used. The need for rest and return to usual activities after the acute phase of the infection may reasonably be based on the person's general energy levels. Nevertheless, in an effort to decrease the risk of splenic rupture experts advise avoidance of contact sports and other heavy physical activity, especially when involving increased abdominal pressure or the Valsalva maneuver (as in rowing or weight training), for at least the first 3–4 weeks of illness or until enlargement of the spleen has resolved, as determined by a treating physician.

One such development is in the delivery of doxorubicin. While it is an effective inducer of apoptosis, doxorubicin is quickly filtered out of the body. By loading a PEG-liposome with doxorubicin the circulation time and localization to tumors greatly increases. Cancerous tumors characteristically have extensive angiogenesis and leaky vasculatures, which causes the PEG-liposomes to naturally accumulate in the tumor. This also allows for patients to receive lower and fewer doses of the drug and experience fewer side effects. This is also being attempted with nanoparticles but has not been tested on FDCS. In 2008 COP plus (PEG)-liposomal doxorubicin went into a clinical trial for an FDCS patient to replace the CHOP regimen, and after 5 years the patient remains in CR.

Currently treatment of ARN consists of antiviral therapy administered orally. Typical antiviral agents used include famciclovir, valganciclovir, and valacyclovir. While on these medications, a patient's kidney function should be watched. Some physician's also may administer the antiviral agents via intravitreal delivery. Though controversial, some physicians administer steroids (prednisone) and antithrombotic therapy (aspirin).

Some commonly admistered antiviral agents are as follows:

- Acyclovir

- Famciclovir

- Valacyclovir

- Gancicilovir

- Valganciclovir