Hematological cancers

Spielberger R, Stiff P, Bensinger W, et al. Palifermin for oral mucositis after intensive therapy for hematologic cancers. New Engl J Med 2004 351 2590-2598. 

The malignant lymphomas are hematologic cancers that consist of a cluster of diseases of the lymphoid tissue. The primary malignant cells for lymphomas are lymphocytes of B-cell, T-cell, and NK-cell origin. These cells originate from a small population of... 

CML is a hematologic cancer that results from an abnormal proliferation of an early myeloid progenitor cell.1 The clinical course of CML has three phases chronic phase, accelerated... 

VX-680 is being developed by Vertex in collaboration with Merck. In Jime 2005 it was announced that a Phase 1 trial of VX-680 in hematological cancers had started [164]. This trial will include CML patients in blast crisis. These trials are in addition to the initial clinical trials in sohd tumors. 

Monoclonal antibodies that target various specific antigens can be used to kill the tumor eells expressing speeifie antigens, especially in hematologic cancers. Rituximab, one of the eommonly used monoelonal antibodies, was suggested to mediate its aetion meehanism via antibody-dependent cellular cytotoxieity (ADCC),... 

Several reports have described the anticancer activity of curcumin in a variety of cancer cell lines. In vitro studies have established the activity for curcumin against breast, gastric, hepatic, pancreatic, colorectal, urinary bladder, kidney, prostate, cervical, ovarian, uterine, lung, oral, thymic, and skin cancers. Besides these cancer types, curcumin has shown in vitro therapeutic efficacy against hematological cancers including leukemia, lymphoma, and multiple myeloma. One of our early studies established that the antiproliferative effect of curcumin in human breast cancer cell lines, including hormone-dependent, hormone-independent,... 

Mercaptopurine and thioguanine are both given orally (Table 55-3) and excreted mainly in the urine. However, 6-MP is converted to an inactive metabolite (6-thiouric acid) by an oxidation catalyzed by xanthine oxidase, whereas 6-TG requires deamination before it is metabolized by this enzyme. This factor is important because the purine analog allopurinol, a potent xanthine oxidase inhibitor, is frequently used with chemotherapy in hematologic cancers to prevent hyperuricemia after tumor cell lysis. It does this by blocking purine oxidation, allowing excretion of cellular purines that are relatively more soluble than uric acid. Nephrotoxicity and acute gout produced by excessive uric acid are thereby prevented. Simultaneous therapy with allopurinol and 6-MP results in excessive toxicity unless the dose of mercaptopurine is reduced to 25% of the usual level. This effect does not occur with 6-TG, which can be used in full doses with allopurinol. 

Osteolytic tumors may induce bone destruction either through local invasion, or by a secondary metastatic bone disease. The most frequent types of primary tumors that develop into metastatic bone disease are, in the order of prevalence breast, prostate, thyroid, kidney, and bronchial tumors, whereas esophageal, gastrointestinal and rectal tumors are much less metastatic [11]. Very often, the destruction of bone in a metastatic bone disease leads to hypercalcemia of malignancy, which also responds to BPs. In addition, hematological cancers such as... 

Palifermin (r-KGF) Kepivance (Amgen) Oral mucositis in hematologic cancer with chemotherapy and radiation therapy and bone marrow transplant... 

Novick SC, Warrell RP Jr. Arsenicals in hematologic cancers. Semin Oncol 2000 27(5) 495-501. 

The mechanism by which IFN-a exerts antitumor activity is unclear, particularly in hematological cancers. In melanoma and renal cell carcinoma, antitumor effects may be mediated by augmented immune responses including activation of natural killer lymphocytes and enhanced expression of cell surface antigens (e.g., MHC I and II). However, these mechanisms have not been decisively proved. 

O Brien SN, Blijlevens NMA, Mahfouz TH, Anaissie EJ. Infections in patients with hematological cancer Recent developments. Hematology (Am Soc Hematol Educ Program) 2003 438-472. 

Bensinger WI, Martin PJ, Storer B, et al. Transplantation of bone marrow as compared with peripheral blood cells from HLA-identical relatives in patients with hematologic cancers. N Engl J Med 2001 344 175-181. 

No statistically significantly elevated hematological cancer SMR was obtained for male workers compared to either local (SMR=263 no Cl 3 observed, 1.1 expected) or national (SMR=375 no Cl ... 

Hematologic cancer mortality (including lymphatic and hematopoietic cancers) Swedish capacitor manufacturing male workers employed 6 months versus Swedish national rates 142 1965-1982 1965-1978 (mean exposure 6.5 yrs) Observed versus expected 1 observed case The report identified one case of malignant lymphoma, expected number of cases was not reported, but the numbers of deaths from cancers was reported to correspond well with those expected. Median latency time=13 years. Gustavsson et al. 1986... 

Search for microsatellite instability in leukemia and lymphoma has revealed that this phenomenon is rare among hematological cancers, with the exception of lymphoid tumors in immunosuppressed patients and in lymphomas derived from mucosa-associated lymphoid tissue (Fey, 1997), diseases which are both usually preceded by a benign B-cell hyperplasia state. 

Immunosuppressive effects Glucocorticoids inhibit some of the mechanisms involved in cell-mediated immunologic functions, especially those dependent on lymphocytes. These agents are actively lymphotoxic and are important in the treatment of hematologic cancers. The drugs do not interfere with the development of normal acquired immunity but delay rejection reactions in patients with organ transplants. 

Ifosamide currently is used as third-line therapy against testicular cancer, although it also has shown activity in a number of solid tumors and hematologic cancers. Patients on ifosfamide (but not cyclophosphamide) commonly exhibit central nervous system (CNS) toxicity. In severe forms, CNS depression can progress to coma and death. 

The second-generation of HDAC inhibitors have shown improved potency over vorinostat, and these include the indole-based dacinostat and panobinostat (http // www.novartisoncology.com/research-innovation/pipelineJsp) [16] originated from Novartis. Both agents inhibit HDAC and the proliferation of cancer cell lines at low nanomolar concentrations and have demonstrated efficacy in a number of solid tumor xenografic models. Dacinostat was advanced to phase I clinical trials in 2002 but discontinued in 2005. Panobinostat is currently in phase 11/111 studies for the treatment of hematological cancers. 

Major Applications Diagnosis of hematologic cancer, nongastric diseases, detection of genetically modified wheat, chromosomes, gene expression, nucleic acid, hepatitis A virus, avian influenza vims subtype H5 and H5Nl,io SARS virus, herpex simplex virus ... 

Shivapurkar, N. Stasmy, V. Takahashi, T. Suzuki, M. Echebiri, C. Reddy, J. Gazdar, A. F. Novel real-time PCR assay using a universal molecular marker for diagnosis of hematologic cancers. Int. J. Cancer 2005,116, 656-660. 

Regenerative medicine is well established in the treatment of many nonsur-gical conditions. Hematopoietic stem cell transplants for hematological cancers. 

In 1957, Thomas and Ferrebee published a report on six patients with end-stage hematologic cancer who received extensive radiation and intravenous marrow cells from healthy donors (Thomas et al. 1957). This pioneering experience in human hematopoietic transplantation led to engraftment in only one case. One year later, Kurnick described the first two cases of autologous transplantation of human marrow cells to treat radiation toxicity. 

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