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In November 2013, ibrutinib was approved by the US FDA for treating MCL.
Other targeted agents include the proteasome inhibitor bortezomib, mTOR inhibitors such as temsirolimus, and the P110δ inhibitor GS-1101.
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.
Immune-based therapy is dominated by the use of the rituximab monoclonal antibody, sold under the trade name Rituxan (or as Mabthera in Europe and Australia). Rituximab may have good activity against MCL as a single agent, but it is typically given in combination with chemotherapies, which prolongs response duration. There are newer variations on monoclonal antibodies combined with radioactive molecules known as Radioimmunotherapy (RIT). These include Zevalin and Bexxar. Rituximab has also been used in small numbers of patients in combination with thalidomide with some effect. In contrast to these antibody-based 'passive' immunotherapies, the field of 'active' immunotherapy tries to activate a patient's immune system to specifically eliminate their own tumor cells. Examples of active immunotherapy include cancer vaccines, adoptive cell transfer, and immunotransplant, which combines vaccination and autologous stem cell transplant. Though no active immunotherapies are currently a standard of care, numerous clinical trials are ongoing.
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.
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.
"MALT lymphoma" is exquisitely immunotherapy sensitive. Chemotherapy is reserved for those uncommon patients with disseminated disease at presentation or lack of response to local treatment. Rituximab, the anti-CD20 chimeric antibody, is a key component of therapy. Responses vary from 55% to 77% with monotherapy and 100% in combination with chemotherapy. Oral alkylating agents such as cyclophosphamide or chlorambucil have been administered for a median duration of 12 months with high rates of disease control (CR up to 75%) but appear not to be active in t(11;18) disease. The purine nucleoside analogs fludarabine and cladribine also demonstrate activity, the latter conferring a CR rate of 84% (100% in those with gastric primaries) in a small study. A pivotal study of rituximab plus chlorambucil compared with chlorambucil alone (IELSG-19 study, n = 227) demonstrated a significantly higher CR rate (78% vs. 65%; p = 0.017) and 5-year EFS (68% vs. 50%; p = 0.024) over chlorambucil alone. However, 5-year OS was not improved (88% in both arms). First-line treatment of choice is generally rituximab in combination with single alkylating agents or fludarabine, or a combination of all three drugs. The final results of this study, including the later addition of a rituximab-alone arm, are pending.
Two other genetic alterations are known:
- t(1;14)(p22;q32), which deregulates BCL10, at the locus 1p22.
- t(14;18)(q32;q21), which deregulates MALT1, at the locus 18q21.
These seem to turn on the same pathway as API2-MLT (i.e., that of NF-κB). They both act upon IGH, which is at the locus 14q32.
Most histiocytomas will regress within two or three months. Surgical removal may be necessary if the tumor does not regress or if it is growing rapidly to a large size. Histiocytomas should never be treated with an intralesional injection of a corticosteroid, as remission relies on recognition of the tumour by the body's immune system which is suppressed by steroids.
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.
Guidelines for management of patients up to 18 years with Langerhans cell histiocytosis has been suggested. Treatment is guided by extent of disease. Solitary bone lesion may be amenable through excision or limited radiation, dosage of 5-10 Gys for children, 24-30 Gys for adults. However systemic diseases often require chemotherapy. Use of systemic steroid is common, singly or adjunct to chemotherapy. Local steroid cream is applied to skin lesions. Endocrine deficiency often require lifelong supplement e.g. desmopressin for diabetes insipidus which can be applied as nasal drop. Chemotherapeutic agents such as alkylating agents, antimetabolites, vinca alkaloids either singly or in combination can lead to complete remission in diffuse disease.
Treatment with chemotherapy has been used with some success, particularly using lomustine, prednisone, doxorubicin, and cyclophosphamide. Because of the rapid progression of this aggressive disease, the prognosis is very poor.
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.
Excellent for single-focus disease. With multi-focal disease 60% have a chronic course, 30% achieve remission and mortality is up to 10%.
Treatment for erythroleukemia generally follows that for other types of AML, not otherwise specified. It consists of chemotherapy, frequently consisting of
cytarabine, daunorubicin, and idarubicin. It can also involve bone marrow transplantation.
Most patients with "ETV6-ACSL6"-related disease present with findings similar to eosinophilia, hypereosinophila, or chronic eosinophilic leukemia; at least 4 cases presented with eosinophilia plus findings of the red blood cell neoplasm, polycythemia vera; three cases resembled acute myelogenous leukemia; and one case presented with findings of a combined Myelodysplastic syndrome/myeloproliferative neoplasm. Best treatments for "ETV6-ACSL6"-related disease are unclear. Patients with the polycythemia vera form of the disease have been treated by reducing the circulating red blood cell load by phlebotomy or suppressing red blood cell formation using hydroxyurea. Individual case studies report that "ETV6-ACSL6"-associated disease is insensitive to tyrosine kinase inhibitors. Best treatment currently available, therefore, may involve chemotherapy and bone marrow transplantion.
The typical patient with angioimmunoblastic T-cell lymphoma (AITL) is either middle-aged or elderly, and no gender preference for this disease has been observed. AITL comprises 15–20% of peripheral T-cell lymphomas and 1–2% of all non-Hodgkin lymphomas.
Patients with hematological disease related to the cited "FLT3" fusion genes present with either a myeloid or lymphoid neoplasm plus eosinophilia. Four of 6 patients with "ETV6-FLT3"-related disease, a patient with "GOLGB1-FLT3"-related disease, and a patient with "TRIP11-FLT3"-related disease presented with findings similar to T-cell lymphoma while a patient with "SPTBN1-FLT3"-related disease had findings of chronic myelogenous leukemia. Two patients with "ETV6-FLT3"-related disease experienced complete hematologic remissions when treated with a multi-kinase inhibitor, sunitinib, that has inhibitory activity against FLT3 protein. However, these remissions were short-lived. A third patient with "ETV6-FLT3"-related disease was treated with a similarly active kinase inhibitor, sorafenib. This patient achieved a complete hematological response and was then given a hematopoietic stem cell transplantation. The latter treatment regimen, FLT3 inhibitor followed by hematopoietic stem cell transplantation, may be the best approach currently available for treating "FLT3"-releated hematological disease.
Splenic marginal zone lymphoma (SMZL) is a type of cancer (specifically a lymphoma) made up of B-cells that replace the normal architecture of the white pulp of the spleen. The neoplastic cells are both small lymphocytes and larger, transformed lymphoblasts, and they invade the mantle zone of splenic follicles and erode the marginal zone, ultimately invading the red pulp of the spleen. Frequently, the bone marrow and splenic hilar lymph nodes are involved along with the peripheral blood. The neoplastic cells circulating in the peripheral blood are termed villous lymphocytes due to their characteristic appearance.
Under older classification systems, the following names were used:
Interdigitating dendritic cell sarcoma is a form of malignant histiocytosis affecting dendritic cells.
It can present in the spleen. It can also present in the duodenum.
Thyroidectomy and neck dissection show good results in early stages of SCTC. However, due to highly aggressive phenotype, surgical treatment is not always possible. The SCTC is a radioiodine-refractory tumor. Radiotherapy might be effective in certain cases, resulting in relatively better survival rate and quality of life. Vincristine, Adriamycin, and bleomycin are used for adjuvant chemotherapy, but their effects are not good enough according to published series.
Langhans cells are often found in transbronchial lung biopsies or lymph node biopsies in patients suffering from sarcoidosis.
Langhans giant cells (also known as Pirogov-Langhans cells) are large cells found in granulomatous conditions.
They are formed by the fusion of epithelioid cells (macrophages), and contain nuclei arranged in a horseshoe-shaped pattern in the cell periphery.
Although traditionally their presence was associated with tuberculosis, they are not specific for tuberculosis or even for mycobacterial disease. In fact, they are found in nearly every form of granulomatous disease, regardless of etiology.
Research into AM functionality has been on the rise since AMs are one of the first lines of a defense against invasive pathogens. One of the most prominent fields is investigating liposomes as deliverers of antibiotics for treatment of respiratory intracellular infections. Intracellular parasites, such as M. tuberculosis, C. pneumoniae, L. monocytogenes, L. pneumophila, and F. tularensis, (to name a few) are taken up by AMs via phagocytosis, but are resistant to the biocidal mechanisms of AMs and can survive intracellularly, thus inducing severe respiratory infections. Pulmonary tuberculosis is caused by M. tuberculosis, and is now a major infectious disease worldwide and its incidence is increasing, especially in association with the AIDS pandemic. For sterilization of intracellular parasites in AMs, antibiotics are normally given orally or intravenously, but much of the antibiotics disperse to many different tissues, diminishing its effectiveness. Pulmonary administration of mannosylated liposomes is a much more direct, efficient route in targeting AMs; it enhances antimicrobial effect, reduces the dosage needed, and avoids unnecessary distribution to the blood. Since mannose receptors are exclusively expressed on the surface of AM, mannosylation of liposomes is an appealing approach to cell-selective targeting to AM. The efficacy of pulmonary administration of ciprofloxacin (CPFX) incorporated into mannosylated liposomes (mannosylated CPFX-lipososomes) was examined in rats, and determined to be an efficient means to target AMs.
Hepatosplenic T-cell lymphoma is a rare and generally incurable form of lymphoma.
Hepatosplenic T-cell lymphoma is a systemic neoplasm comprising medium-sized cytotoxic T-cells that show a significant sinusoidal infiltration in the liver, spleen, and bone marrow.
This type of carcinoma is commonly managed by local resection, cryotherapy, topical chemotherapy, and radiotherapy. Multimodal therapy has been shown to improve both visual prognosis and survival.
Mohs micrographic surgery has become the treatment of choice for this form of cancer. When used as the primary treatment modality for sebaceous carcinoma of the eyelid, Mohs surgery is associated with significantly lower local and distant recurrence rates.