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.

Surgical treatment is recommended for cats and dogs diagnosed with primary liver tumors but not metastasis to the liver. There are not many treatment options for animals who have multiple liver lobes affected.

Newer cases are also starting to be treated by taxotere and gemcitabine. Taxotere is similar to Oncovin used in CHOP; it irreversibly binds beta tubulin halting formation of microtubules. Taxotere has an added benefit though; it also phosphorylates bcl-2 to halt the anti-apoptotic pathway. The dual effect of taxotere on integral cancer pathways makes it a more potent drug than Oncovin. Gemcitabene is a nucleoside analog and when incorporated into DNA during replication leads to apoptosis; the fluorine on the 2’ carbon atom stops other nucleosides from attaching. The most important part of this combination therapy, however, is the synergism between the drugs. While researchers are not entirely sure of the mechanism, there is evidence of synergistic effects of taxotere and gemcitabine when used in combination. This allows for decreased dosages of each single agent with an increased apoptotic response.

The Stehlin Foundation currently offers DSRCT patients the opportunity to send samples of their tumors free of charge for testing. Research scientists are growing the samples on nude mice and testing various chemical agents to find which are most effective against the individual's tumor.

Patients with advanced DSRCT may qualify to participate in clinical trials that are researching new drugs to treat the disease.

Chemotherapy (typically the agent Mitomycin C) may be infused directly into the abdominal cavity after cytoreductive surgery to kill remaining microscopic cancerous tumors and free floating cells. The heated chemotherapy (HIPEC) is perfused throughout the abdominal cavity for an hour or two as the last step in the surgery, or ports are installed to allow circulation and/or drainage of the chemicals for one to five days after surgery, known as early postoperative intraperitoneal chemotherapy (EPIC). EPIC may be given in multiple cycles for several months after surgery.

Systemic chemotherapy may be administered as additional or adjuvant treatment. Due to the increased availability of new chemotherapies developed for colon and colorectal cancer patients, some patients have experienced stability in tumor growth with systemic chemotherapy. Systemic chemotherapy is reserved for patients with advanced disease, recurrent disease, or disease that has spread to the lymph nodes or distant sites.

This disease may recur following surgery and chemotherapy. Periodic post operative CT scans and tumor marker laboratory tests are used to monitor the disease for any tumor regrowth.

Treatment includes chemotherapy and, where practical, removal of the tumor with the affected organ, such as with a splenectomy. Splenectomy alone gives an average survival time of 1–3 months. The addition of chemotherapy, primarily comprising the drug doxorubicin, alone or in combination with other drugs, can increase the average survival time to 2-4 months, or more.

A more favorable outcome has been demonstrated in recent research conducted at University of Pennsylvania Veterinary School, in dogs treated with a compound derived from the Coriolus versicolor (commonly known as "Turkey Tail") mushroom:

“We were shocked,” Cimino Brown said. “Prior to this, the longest reported median survival time of dogs with hemangiosarcoma of the spleen that underwent no further treatment was 86 days. We had dogs that lived beyond a year with nothing other than this mushroom as treatment.”There were not statistically significant differences in survival between the three dosage groups, though the longest survival time was highest in the 100 mg group, at 199 days, eclipsing the previously reported survival time.

The results were so surprising, in fact, that the researchers asked Penn Vet pathologists to recheck the dogs’ tissue biopsies to make sure that the dogs really had the disease.

“They reread the samples and said, yes, it’s really hemangiosarcoma,” Cimino Brown said.

Chemotherapy is available for treating hemangiosarcoma, but many owners opt not to pursue that treatment once their dog is diagnosed.

“It doesn’t hugely increase survival, it’s expensive and it means a lot of back and forth to the vet for the dog,” Cimino Brown said. “So you have to figure in quality of life.”

This treatment does not always work. So, one should always be prepared for their pet to have the same survival time as a dog who is untreated.

Visceral hemangiosarcoma is usually fatal even with treatment, and usually within weeks or, at best, months. In the skin, it can be cured in most cases with complete surgical removal as long as there is not visceral involvement.

Surgery may be difficult due to the location of these tumors. Surgery alone often leads to recurrence. Chemotherapy is very effective for TVTs. The prognosis for complete remission with chemotherapy is excellent. The most common chemotherapy agents used are vincristine, vinblastine, and doxorubicin. Radiotherapy may be required if chemotherapy does not work.

The standard of care for mucinous adenocarcinoma with clinical condition PMP involves cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), by surgical oncologists who specialize in treating PMP. Some surgeons also apply early post-operative intraperitonial chemotherapy (EPIC), adjunct to surgical cytoreduction and HIPEC. In situations where surgery is not required immediately, patients can be monitored via CT scans, tumor marker laboratory tests, and physical symptoms, to determine when, and if, surgery is warranted. Although some surgical procedures may be rather extensive, patients can and do recover from surgery, and the majority of these patients can and do live productive lives.

In debulking, the surgeon attempts to remove as much tumor as possible. CRS or cytoreductive surgery involves surgical removal of the peritoneum and any adjacent organs which appear to have tumor seeding. Since the mucus tends to pool at the bottom of the abdominal cavity, it is common to remove the ovaries, fallopian tubes, uterus, and parts of the large intestine. Depending upon the spread of the tumor, other organs might be removed, including but not limited to the gallbladder, spleen, and portions of the small intestine and/or stomach. For organs that cannot be removed safely (like the liver), the surgeon strips off the tumor from the surface.

The prognosis for DSRCT remains poor. Prognosis depends upon the stage of the cancer. Because the disease can be misdiagnosed or remain undetected, tumors frequently grow large within the abdomen and metastasize or seed to other parts of the body.

There is no known organ or area of origin. DSRCT can metastasize through lymph nodes or the blood stream. Sites of metastasis include the spleen, diaphragm, liver, large and small intestine, lungs, central nervous system, bones, uterus, bladder, genitals, abdominal cavity, and the brain.

A multi-modality approach of high-dose chemotherapy, aggressive surgical resection, radiation, and stem cell rescue improves survival for some patients. Reports have indicated that patients will initially respond to first line chemotherapy and treatment but that relapse is common.

Some patients in remission or with inoperable tumor seem to benefit from long term low dose chemotherapy, turning DSRCT into a chronic disease.

Due to the high risk of recurrence and ensuing problems, close monitoring of dogs undergoing chemotherapy is important. The same is true for dogs that have entered remission and ceased treatment. Monitoring for disease and remission/recurrence is usually performed by palpation of peripheral lymph nodes. This procedure detects gross changes in peripheral lymph nodes. Some of the blood tests used in diagnosing lymphoma also offer greater objectivity and provide an earlier warning of an animal coming out of remission.

Complete cure is rare with lymphoma and treatment tends to be palliative, but long remission times are possible with chemotherapy. With effective protocols, average first remission times are 6 to 8 months. Second remissions are shorter and harder to accomplish. Average survival is 9 to 12 months. The most common treatment is a combination of cyclophosphamide, vincristine, prednisone, L-asparaginase, and doxorubicin. Other chemotherapy drugs such as chlorambucil, lomustine (CCNU), cytosine arabinoside, and mitoxantrone are sometimes used in the treatment of lymphoma by themselves or in substitution for other drugs. In most cases, appropriate treatment protocols cause few side effects, but white blood cell counts must be monitored.

Allogeneic and autologous stem cell transplantations (as is commonly done in humans) have recently been shown to be a possible treatment option for dogs. Most of the basic research on transplantation biology was generated in dogs. Current cure rates using stem cell therapy in dogs approximates that achieved in humans, 40-50%.

When cost is a factor, prednisone used alone can improve the symptoms dramatically, but it does not significantly affect the survival rate. The average survival times of dogs treated with prednisone and untreated dogs are both one to two months. Using prednisone alone can cause the cancer to become resistant to other chemotherapy agents, so it should only be used if more aggressive treatment is not an option.

Isotretinoin can be used to treat cutaneous lymphoma.

Treatment of small melanomas is often not necessary, but large tumors can cause discomfort and are usually surgically removed. Cisplatin and cryotherapy can be used to treat small tumors less than 3 centimeters, but tumors may reoccur. Cimetidine, a histamine stimulator, can cause tumors to regress in some horses, but may take up to 3 months to produce results and multiple treatments may be needed throughout the horse's life. There are few viable treatment options for horses with metastatic melanoma. However, gene therapy injections utilizing interleukin-12 and 18-encoding DNA plasmids have shown promise in slowing the progression of tumors in patients with metastatic melanoma.

Treatment is dependent if the lymphoma is causing issues in regards to the overall health of the individual. Since this a slow moving cancer, many patients start treatment when the symptoms appear. If the individual tests positive for hepatitis C, then anti-viral treatment is suggested since it will often get rid of the lymphoma as well. If further treatment is required the options include chemotherapy, monoclonal antibodies, and/or radiation. Radiation therapy is used for stage I and II nodal marginal zone NHL. Clinical trials show success in treatment when using drugs such as bendamustine and lenalidomida in combination with rituximab.

The original route of treatment for MALT is antibiotics to treat an underlying infection such as H.pylori. H.pylori is directly related to the development of this lymphoma. Since most patients respond well to this treatment, then no further treatment is needed. If the lymphoma is not linked to an infection, then radiotherapy and chemotherapy are needed. If the disease is more advanced, then immunoradiotherapy with chemotherapy will be needed. Among the common first-line treatments are bendamustine plus rituximab and R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Recently, antibiotic therapy such as doxycycline has been shown to be effective in marginal zone lymphoma that affects the area around the eye ("ocular adnexal marginal zone lymphoma").

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.

After surgery, adjuvant chemotherapy with gemcitabine or 5-FU can be offered if the person is sufficiently fit, after a recovery period of one to two months. In people not suitable for curative surgery, chemotherapy may be used to extend life or improve its quality. Before surgery, neoadjuvant chemotherapy or chemoradiotherapy may be used in cases that are considered to be "borderline resectable" (see Staging) in order to reduce the cancer to a level where surgery could be beneficial. In other cases neoadjuvant therapy remains controversial, because it delays surgery.

Gemcitabine was approved by the United States Food and Drug Administration (FDA) in 1997, after a clinical trial reported improvements in quality of life and a 5-week improvement in median survival duration in people with advanced pancreatic cancer. This was the first chemotherapy drug approved by the FDA primarily for a nonsurvival clinical trial endpoint. Chemotherapy using gemcitabine alone was the standard for about a decade, as a number of trials testing it in combination with other drugs failed to demonstrate significantly better outcomes. However, the combination of gemcitabine with erlotinib was found to increase survival modestly, and erlotinib was licensed by the FDA for use in pancreatic cancer in 2005.

The FOLFIRINOX chemotherapy regimen using four drugs was found more effective than gemcitabine, but with substantial side effects, and is thus only suitable for people with good performance status. This is also true of protein-bound paclitaxel (nab-paclitaxel), which was licensed by the FDA in 2013 for use with gemcitabine in pancreas cancer. By the end of 2013, both FOLFIRINOX and nab-paclitaxel with gemcitabine were regarded as good choices for those able to tolerate the side-effects, and gemcitabine remained an effective option for those who were not. A head-to-head trial between the two new options is awaited, and trials investigating other variations continue. However, the changes of the last few years have only increased survival times by a few months. Clinical trials are often conducted for novel adjuvant therapies.

CHOP frequently induces remission initially, but most patients relapse and die within two years. Autologous bone marrow transplantation is currently being investigated in the treatment of hepatosplenic lymphoma. Allogeneic bone marrow transplant has been proven to attain remission for over five years and possibly cure hepatosplenic lymphoma.

Splenectomy can produce long-term remissions in patients whose spleens seem to be heavily involved, but its success rate is noticeably lower than cladribine or pentostatin. Splenectomies are also performed for patients whose persistently enlarged spleens cause significant discomfort or in patients whose persistently low platelet counts suggest Idiopathic thrombocytopenic purpura.

Bone marrow transplants are usually shunned in this highly treatable disease because of the inherent risks in the procedure. They may be considered for refractory cases in younger, otherwise healthy individuals. "Mini-transplants" are possible.

People with anemia or thrombocytopenia may also receive red blood cells and platelets through blood transfusions. Blood transfusions are always irradiated to remove white blood cells and thereby reduce the risk of graft-versus-host disease. Patients may also receive a hormone to stimulate production of red blood cells. These treatments may be medically necessary, but do not kill the hairy cells.

People with low neutrophil counts may be given filgrastim or a similar hormone to stimulate production of white blood cells. However, a 1999 study indicates that routine administration of this expensive injected drug has no practical value for HCL patients after cladribine administration. In this study, patients who received filgrastim were just as likely to experience a high fever and to be admitted to the hospital as those who did not, even though the drug artificially inflated their white blood cell counts. This study leaves open the possibility that filgrastim may still be appropriate for patients who have symptoms of infection, or at times other than shortly after cladribine treatment.

Although hairy cells are technically long-lived, instead of rapidly dividing, some late-stage patients are treated with broad-spectrum chemotherapy agents such as methotrexate that are effective at killing rapidly dividing cells. This is not typically attempted unless all other options have been exhausted and it is typically unsuccessful.

When primary or secondary resistance invariably develops, salvage therapy is considered. Allogeneic stem cell transplantation can induce durable remissions for heavily pre-treated patients.

Treatment of this disorder involves treatment of the underlying cancer.

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.

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.

The theory behind splenectomy in JMML is that the spleen may trap leukemic cells, leading to the spleen's enlargement, by harboring dormant JMML cells that are not eradicated by radiation therapy or chemotherapy for the active leukemia cells, thus leading to later relapse if the spleen is not removed. However, the impact of splenectomy on post-transplant relapse, though, is unknown. The COG JMML study includes splenectomy as a standard component of treatment for all clinically stable patients. The EWOG-MDS JMML study allows each child’s physician to determine whether or not a splenectomy should be done, and large spleens are commonly removed prior to bone marrow transplant. When a splenectomy is scheduled, JMML patients are advised to receive vaccines against "Streptococcus pneumoniae" and "Haemophilus influenza" at least 2 weeks prior to the procedure. Following splenectomy, penicillin may be administered daily in order to protect the patient against bacterial infections that the spleen would otherwise have protected against; this daily preventative regimen will often continue indefinitely.

The high cure rates and long survival of many patients with Hodgkin's lymphoma has led to a high concern with late adverse effects of treatment, including cardiovascular disease and second malignancies such as acute leukemias, lymphomas, and solid tumors within the radiation therapy field. Most patients with early-stage disease are now treated with abbreviated chemotherapy and involved-field radiation therapy rather than with radiation therapy alone. Clinical research strategies are exploring reduction of the duration of chemotherapy and dose and volume of radiation therapy in an attempt to reduce late morbidity and mortality of treatment while maintaining high cure rates. Hospitals are also treating those who respond quickly to chemotherapy with no radiation.

In childhood cases of Hodgkin's lymphoma, long-term endocrine adverse effects are a major concern, mainly gonadal dysfunction and growth retardation. Gonadal dysfunction seems to be the most severe endocrine long-term effect, especially after treatment with alkylating agents or pelvic radiotherapy.

Should treatment be started it should address both the paraprotein level and the lymphocytic B-cells.

In 2002, a panel at the International Workshop on Waldenström's Macroglobulinemia agreed on criteria for the initiation of therapy. They recommended starting therapy in patients with constitutional symptoms such as recurrent fever, night sweats, fatigue due to anemia, weight loss, progressive symptomatic lymphadenopathy or spleen enlargement, and anemia due to bone marrow infiltration. Complications such as hyperviscosity syndrome, symptomatic sensorimotor peripheral neuropathy, systemic amyloidosis, kidney failure, or symptomatic cryoglobulinemia were also suggested as indications for therapy.

Treatment includes the monoclonal antibody rituximab, sometimes in combination with chemotherapeutic drugs such as chlorambucil, cyclophosphamide, or vincristine or with thalidomide. Corticosteroids, such as prednisone, may also be used in combination. Plasmapheresis can be used to treat the hyperviscosity syndrome by removing the paraprotein from the blood, although it does not address the underlying disease. Ibrutinib is another agent that has been approved for use in this condition.

Recently, autologous bone marrow transplantation has been added to the available treatment options.

Most patients with T-cell prolymphocytic leukemia require immediate treatment.

T-cell prolymphocytic leukemia is difficult to treat, and it does not respond to most available chemotherapeutic drugs. Many different treatments have been attempted, with limited success in certain patients: purine analogues (pentostatin, fludarabine, cladribine), chlorambucil, and various forms of combination chemotherapy regimens, including cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), etoposide, bleomycin (VAPEC-B).

Alemtuzumab (Campath), an anti-CD52 monoclonal antibody that attacks white blood cells, has been used in treatment with greater success than previous options. In one study of previously treated people with T-PLL, people who had a complete response to alemtuzumab survived a median of 16 months after treatment.

Some patients who successfully respond to treatment also undergo stem cell transplantation to consolidate the response.