**4. Acute lymphoblastic leukemia (ALL)**

The classical main treatment for adult acute lymphoblastic leukemia (ALL) is *chemotherapy* drugs and in some patients the transplant of stem cells in adult patients has good results. Advance enhancement maybe calls for a diverse approach from conventional chemotherapy, such as target drugs with TKI (imatinib) and/or immunotherapy.

ALL with Philadelphia chromosome-positive (Ph+) have been noted with impressive response to intensive chemotherapy and imatinib [27].

*CD20 is a B cell*-specific surface antigen on mature B-ALL and precursor B-ALL, as well as in lymphoblastic lymphoma, would manage the probability of rituximab response. The introduction of target therapy (rituximab) in combination with chemotherapy (Hyper-CVAD) (rituximab with hyperfractionated cyclophosphamide, doxorubicin, vincristine and dexamethasone) in lymphoma or leukemia, reported complete remission rate of 90% with minimal toxicity [28, 29].

Acute lymphoblastic leukemia blast cells express specific antigens for CD22 in 90% of patients and have amazing clinical action indeed among intensely before treatment of elderly B-ALL patients and refractory and relapsed B-ALL patients after treatment with inotuzumab ozogamicin. Combination of inotuzumab ozogamicin with other treatments after chemotherapy may too possibly improve clinical outcomes [30].

Blinatumomab: is a CD3 and CD19-directed, to activate a B-cell specific inflammatory and cytolytic response. In 2006 FDA approved Blinatumomab for refractory and relapsed ALL [31]. Blinatumomab activates endogenous T cells by connecting CD19 on benign and malignant B cells with CD3 in the T-cell receptor complex in combination with chemotherapy or as single agents, in preclinical and clinical settings have produced varying response to induce tumor cell lysis via complement-dependent cytotoxicity or with antibody, induce cell death [32, 33].

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*Target Therapy in Hematological Malignancies DOI: http://dx.doi.org/10.5772/intechopen.84696*

period within 4–6 months [35].

related toxicity.

response [38].

**5.2 Dasatinib (Sprycel)**

treated with dasatinib [40].

**5.1 Imatinib (Gleevec)**

**5. Chronic myeloid (***Myelogenous***) leukemia (CML)**

use include nilotinib, dasatinib, bosutinib and ponatinib.

Chronic *Myelogenous* Leukemia (CML) is a clonal myeloproliferative disorder characterized by the increased and unregulated growth of *myeloid* cells due to translocation between long arms of chromosomes 9 and 22t (9;22) that generates tyrosine kinase BCR-ABL1 [34]. CML classified into 3 phases; chronic stable phase (CP) which the myeloid cell series is expanded but cellular differentiation is maintained and effortlessly controlled with treatment for a period that can last for 36–60 months but the accelerated phase (AP) can lasts for less than 12 months. Blast phase (BP) are still poorly understood, characterized by rapid expansion of myeloid or lymphoid with presence of more than 20% blast cells in the peripheral blood or bone marrow resulting in manifestation of ALL or AML and death in short

Chronic myeloid (*Myelogenous)* leukemia treatment progressed significantly through the advancement of tyrosine kinase inhibitors (TKIs), particularly the presentation of imatinib into the clinical use. Imatinib is the drug of choice of the first generation in the chronic phase of CML and considered the golden standard target therapy in CML. The second generations also currently available for clinical

To maintain patients in remission and prevent progression of disease into accelerated and blast phases are the main treatment goals of chronic myeloid leukemias and keep the patients free of complications and with minimal drug

Target therapy with TKIs and allogenic bone marrow transplantation, play

Imatinib mesylate (IM), a phenylaminopyrimidine TKI that is the first drug of its class characterized by BCR-ABL TKI has excellent changes in the strategy of treatment of CML in the last 20 years. In May 2001, FDA has approved imatinib for the treatment of CML patients. Arthralgia, myalgia, nausea, and fluid retention are the common side effects in imatinib. About 97% complete hematologic response and 83% cytogenetic response was documented after many years of regular follow up of CML patients received imatinib [36, 37]. Patients with hematological or cytogenetic resistance to standard dosage of imatinib (400 mg) were begun with tall dosage (600–800 mg). Some of patients are unlikely to be overcome by high doses due to some specific mutations, in these cases alternative target therapy should be considered for patients fails or with suboptimal

Dasatinib is approved in 2006 as a kinase inhibitor of thiazole carboximide agent and molecular formula C22H26CIN7O2S.H2O with highly powerful dual Abl/Src kinase inhibitor against most imatinib-resistant mutants. Dasatinib considering the excellent treatment option for CML cases in chronic phase and other CML phases who develop resistance or fails response to imatinib and for cases with Ph+ALL [39]. Dasatinib is more than 300 times as powerful as imatinib in restraining unmutated BCR-ABL transcripts in vitro. The incidence of resistance to dasatinib is less than other TKI and the disease progression may be reduced among CML cases

important role in improvement curative percentage of CML patients.

*Advances in Hematologic Malignancies*

leukemia (AML).

immunotherapy.

clinical outcomes [30].

Navitoclax is BCL2 inhibitor by ABT-199 with multiple anti-apoptotic of AML. Its antitumor activity is restricted by adverse effects, which is registered by

Vosaroxin could be a topoisomerase II inhibitor which is one of the important randomized trials exploring therapeutic options for refractory and relapsed AML to date and considered basic for cell survival. Vosaroxin induces DNA destruction and is most successful among elderly patients more than 60 years of age with myelodys-

Lysine-specific demethylase 1 (LSD1) is a histone demethylase. LSD1 inhibition leads to the inhibition of growth and metastasis of tumor and also regulates the differentiation of stem cells and has potential novel treatment in acute myeloid

Panobinostat (LBH589) induces AML cell apoptosis in vitro by inhibiting the expression of repair proteins (e.g., BRCA1, CHK1 and RAD51), increasing the efficiency of cytarabine and daunorubicin, and it is promising in t(8;21) AML due to the pathological AML1/ETO protein that recruits histone deacetylases and in combination with Azacitidine (AZA) doubled the rate of response in high risk patients with CMML, MDS or AML not candidate for stem cell transplantation [25]. Vorinostat (suberoylanilidehydroxamic acid [SAHA]) advances cell cycle inhibition of growth and induces differentiation and cell apoptosis of AML and reported

favorable overall survival in AML patients with FLT3 ITD mutations [26].

The classical main treatment for adult acute lymphoblastic leukemia (ALL) is *chemotherapy* drugs and in some patients the transplant of stem cells in adult patients has good results. Advance enhancement maybe calls for a diverse approach from conventional chemotherapy, such as target drugs with TKI (imatinib) and/or

ALL with Philadelphia chromosome-positive (Ph+) have been noted with

*CD20 is a B cell*-specific surface antigen on mature B-ALL and precursor B-ALL, as well as in lymphoblastic lymphoma, would manage the probability of rituximab response. The introduction of target therapy (rituximab) in combination with chemotherapy (Hyper-CVAD) (rituximab with hyperfractionated cyclophosphamide, doxorubicin, vincristine and dexamethasone) in lymphoma or leukemia, reported

Acute lymphoblastic leukemia blast cells express specific antigens for CD22 in 90% of patients and have amazing clinical action indeed among intensely before treatment of elderly B-ALL patients and refractory and relapsed B-ALL patients after treatment with inotuzumab ozogamicin. Combination of inotuzumab ozogamicin with other treatments after chemotherapy may too possibly improve

Blinatumomab: is a CD3 and CD19-directed, to activate a B-cell specific inflammatory and cytolytic response. In 2006 FDA approved Blinatumomab for refractory and relapsed ALL [31]. Blinatumomab activates endogenous T cells by connecting CD19 on benign and malignant B cells with CD3 in the T-cell receptor complex in combination with chemotherapy or as single agents, in preclinical and clinical settings have produced varying response to induce tumor cell lysis via complement-dependent cytotoxicity or with antibody, induce cell

impressive response to intensive chemotherapy and imatinib [27].

complete remission rate of 90% with minimal toxicity [28, 29].

**4. Acute lymphoblastic leukemia (ALL)**

the FDA for treating chronic lymphocytic leukemia (CLL) and AML [23].

plastic disorder (MDS) or acute myeloid leukemia (AML) [24].

**122**

death [32, 33].
