.Siena S, Sartore-Bianchi A, Trusolino L, et al: Final results of the HERACLES trial in HER2-amplified colorectal cancer. 2017 AACR Annual Meeting. Abstract CT005. Presented April 2, 2017.

http://www.abstractsonline.com/pp8/#!/4292/presentation/12323

S. Siena et al, Targeting the human epidermal growth factor receptor 2 (HER2) oncogene in colorectal cancer. Ann Oncol 2018 May; 29(5): 11081119

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Occasionally, a patient largely responds to two induction chemotherapies but is found to have persistent leukemia cells in the marrow. It is known that without farther intervention, such a patient is destined to relapse within a few months. Studies in 1980s and 1990s demonstrate that effective salvage regimens for relapsed or refractory AML include Ara-C and anthracycline-like compounds as the backbone of the regimens. Combinations that included flu-darabine and/or combinations of both Ara-C and anthracycline-like compounds also demonstrated efficacy and three drug salvage regimens are being studied. Also being explored are targeted agents, and allogeneic SCT, alone of in combinaitons. Prognostic significance of cytogenetic and other markers that can guide this choice is also being explored.

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IVIG is approved by the FDA for use in the treatment of the following diseases: Kawasaki disease, dermato/polymyositis, idiopathic thrombocytopenic purpura (ITP), Guillain-Barre syndrome, polyneuropathy, some viral diseases, and some forms of immune deficiency. The place of IVIG in the treatment of ITP is not well clarified. It does not modify the disease as do steroids and splenectomy, but only gains a temporary rise in platelet counts, until definitive therapy can be planned or accomplished. In addition, a number of alternatives exist, including: Anti-RhoD, vincristine, Rituximab, danazol, high dose pulse steroids and even chemotherapy. IVIG is accordingly best used as a temporary measure, to prepare the patient for spenectomy or while discussions of other treatments take place. It is also occasionally used to wait and see if a spontaneous remission of the ITP occurrs; however, this use is less supported by the literature.
Based on the literature, CMS advises the following:IVIG is indicated for chronic ITP only when all of the following conditions are met:

Prior treatment with corticosteroids and splenectomy;
Duration of illness less than 6 months;
Age of 10 years or older;
No concurrent illness/disease explaining thrombocytopenia; and
Platelet counts persistently at or below 20,000/ml.

The Australian guideline sets the plt. level at 30K and adds preoperative use and use in preagnant women as well as for severe bleeding and other indications.

Anderson D, Ali K, Blanchette V, et al. Guidelines on the use of intravenous immune globulin for hematologic conditions. Transfus Med Rev. 2007;21(2 Suppl 1):S9-56.

George JN, Woolf SH, Raskob GE, Wasser JS, Aledort LM, Ballem PJ, Blanchette VS, Bussel JB, Cines DB, Kelton JG, Lichtin AE, McMillan R, Okerbloom JA, Regan DH, Warrier I: Idiopathic thrombocytopenic purpura: A practice guideline developed by explicit methods for the American Society of Hematology. Blood 88:3, 1996

Download 2011 ITP Pocket Guide[1]

Cines DB, Blanchette VS: Immune thrombocytopenic purpura. N Engl J Med 2002 Mar 28; 346(13): 995-1008

Kahn MJ, McCrae KR: Splenectomy in Immune Thrombocytopenic Purpura: Recent Controversies and Long-term Outcomes. Curr Hematol Rep 2004 Sep; 3(5): 317-23

McMillan R, Durette C: Long-term outcomes in adults with chronic ITP after splenectomy failure. Blood 2004 Aug 15; 104(4): 956-60

Australian Guideline(2007)

http://www.nba.gov.au/ivig/pdf/criteria-qrg.pdf

Alan H. Lazarus^{* Mechanism of action of IVIG in ITP} 2002 Blackwell Science Ltd  Vox Sanguinis Volume 83, Issue Supplement s1, pages 53–55, August 2002

In summary, there is a high degree of interest in the use of sorefenib with other drugs or alone for FLT+ AML but corroborating literature is still very preliminary and at the level of case reports. For this reason, it is still experimental at this time.

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Related haploidentical BMT is an alternative method for expanding the potential pool of stem cell donors; any patient shares one HLA haplotype with each biologic parent or child and siblings or half-siblings have a 50% chance of being haploidentical and 50% chance of not being haploidentical. Despite as an optimal matching as possible, such donors have more subtle genetic differences from the transplanted patient than a properly matched sibling. The more differences between the patient and the donor, they higher is the incidence of graft rejection and severe graft vs. host disease. Thus, the disadvantage of the haploidentical approach has been the high incidence of graft rejection and severe GVHD.

Continued research is needed to better define preferred conditioning regimens, methods and degree of T-cell depletion, and optimal CD34+ cell dose in the allograft, all of which modify the risk and severity of graft versus host disease. Although haploidentical transplantation is a potentially curative option for AML patients lacking a suitable sibling or unrelated donor, experts believe that at this time it should be performed only in experienced centers, within the context of clinical trials, especially in patients with poor-risk AML in CR1.

Alternatives include umbilical cell and related donor transplantation.

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• Normal values for absolute neutrophil count (>1000/microL) and platelet count (>100,000/microL), and independence from red cell transfusion.
• A bone marrow biopsy that reveals no clusters or collections of blast cells. Extramedullary leukemia (e.g., central nervous system or soft tissue involvement) must be absent.
• A bone marrow aspiration reveals normal maturation of all cellular components (i.e., erythrocytic, granulocytic, and megakaryocytic series). There is no requirement for bone marrow cellularity.
• Less than 5 percent blast cells are present in the bone marrow, and none can have a leukemic phenotype (e.g., Auer rods). The persistence of dysplasia is worrisome as an indicator of residual AML but has not been validated as a criterion for remission status.
• The absence of a previously detected clonal cytogenetic abnormality (i.e., complete cytogenetic remission, CRc) confirms the morphologic diagnosis of CR but is not currently a required criterion. However, conversion from an abnormal to a normal karyotype at the time of first CR is an important prognostic indicator, supporting the use of CRc as a criterion for CR in AML.

Some patients may fulfill all of the above criteria for CR but may not recover normal peripheral blood counts. These are denoted as CRi, or CR with insufficient hematological recovery (platelets or neutrophils). CRp describes a subset of patients with CRi, wherein patients fulfill all criteria for CR except that platelet counts are <100,000/microL. Lack of full recovery of counts is of significant concern as it may presage relapse. The survival and relapse rates for patients with CRp appear to be worse than those with a CR, but better than those with a partial remission (PR).

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