**3. From chemotherapy to targeted drugs**

The most recent advances, spanned across the last 3 decades, can be largely attributed to a terrific improvement in technology and a definitely better knowledge of leukemia biology (**Table 4**) [15]. Specifically, after the first recognition of recurrent genomic imbalances in the 1970s, patients' risk of recurrence, and therefore the most appropriate treatment (more or less intensified), were defined by cytogenetic analyses [16–17]. Subsequently, quantitative polymerase chain reaction (PCR) based techniques allowed an accurate and reliable quantitation of the residual


**7**

**Author details**

ALL patients [22].

diseases.

Bologna, Italy

Pier Paolo Piccaluga

Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology, Bologna University School of Medicine,

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*Address all correspondence to: pierpaolo.piccaluga@unibo.it

provided the original work is properly cited.

*Introductory Chapter: A Brief History of Acute Leukemias Treatment*

disease, this becoming a major factor in determining the choice of treatment (more or less intensified chemotherapy, stem cell transplantation, and targeted drugs) especially in ALL [18]. Finally, next generation sequencing, the first AML genome studied in 2008 [19], quickly led to a refined molecular classification of both AML and ALL [20–21], unveiling new therapeutic targets and hopefully nearing the new era of personalized medicine. Indeed, in the current century, a series of amazing new drugs have been licensed for acute leukemia treatment, including tyrosine kinase inhibitors, BCL2 inhibitors, IDH2 inhibitors, demethylating agents, and monoclonal antibodies including the novel bispecific T-cell engagers (**Table 3**). On the other hand, the latest frontier of cellular therapy relies on the chimeric antigen receptor T-cell therapies (CAR-T), firstly demonstrated to be effective in younger

We may certainly expect that further improvements in our understanding of leukemogenesis will lead to later significant success in curing these still terrible

*DOI: http://dx.doi.org/10.5772/intechopen.96439*

#### **Table 4.**

*Evolution of technologies that re-defined leukemia diagnosis and prognostication.*

#### *Introductory Chapter: A Brief History of Acute Leukemias Treatment DOI: http://dx.doi.org/10.5772/intechopen.96439*

*Acute Leukemias*

in mice [10]. This prompted further clinical research in humans and in 1957 Donald Thomas described the first intravenous infusion of bone marrow in humans [11]. In the following decades, tremendous progresses were made and successful bone marrow transplantations were recorded in acute leukemia patients, wither with relapsed/refractory disease and in complete remission [12–14]. By time, bone marrow transplantation evolved to stem cell transplantation, with different sources being available such as marrow, peripheral blood, and umbilical cord blood. At the same time, donation was not limited to siblings but extended to voluntary matched donors, the first registry being funded in UK in 1974, and even only partially

Overall, however, the success of anti-leukemic treatments was achieved not only by developing new drugs and schemes (**Table 2**) [15] but also by dramatically improving supportive cares (**Table 3**) [15], especially as far as blood and derivates transfusion as well as anti-microbe drugs were concerned. Particularly, after the first blood transfusion in a leukemic patient in 1873, the most significant advancement was represented by blood groups description in 1901 by Landsteiner et al. Eventually, in 1937 the first hospital blood bank was established and blood products

The most recent advances, spanned across the last 3 decades, can be largely attributed to a terrific improvement in technology and a definitely better knowledge of leukemia biology (**Table 4**) [15]. Specifically, after the first recognition of recurrent genomic imbalances in the 1970s, patients' risk of recurrence, and therefore the most appropriate treatment (more or less intensified), were defined by cytogenetic analyses [16–17]. Subsequently, quantitative polymerase chain reaction (PCR) based techniques allowed an accurate and reliable quantitation of the residual

1960\* Metaphase cytogenetics; *Peter Nowell* and *David Hungerford* describe the Philadelphia chromosome

1978 Thiopurine methyltransferase polymorphisms related to response and toxicity

compatible ones, in the so called haploidentical transplant (**Table 3**).

such as platelets were successfully administered in 1954 [15].

1670\* Examination of the blood with the compound microscope

1998 Minimal residual disease by the polymerase chain reaction 2001 Classification of AML risk based on cytogenetic features

2016 Genomic Classification and Prognosis in Acute Myeloid Leukemia

*Evolution of technologies that re-defined leukemia diagnosis and prognostication.*

2017 Integration of Next-Generation Sequencing to Treat Acute Lymphoblastic Leukemia

1877 *Paul Ehrlich* introduced histochemical staining

1975 Production of monoclonal antibodies

2008 First whole genome sequencing in AML

1980 Fluorescent in situ hybridization 1985 Polymerase chain reaction 1996 Gene expression arrays

**3. From chemotherapy to targeted drugs**

**Year Development**

1934 Flow cytometry

**6**

*\*Approximately.*

**Table 4.**

disease, this becoming a major factor in determining the choice of treatment (more or less intensified chemotherapy, stem cell transplantation, and targeted drugs) especially in ALL [18]. Finally, next generation sequencing, the first AML genome studied in 2008 [19], quickly led to a refined molecular classification of both AML and ALL [20–21], unveiling new therapeutic targets and hopefully nearing the new era of personalized medicine. Indeed, in the current century, a series of amazing new drugs have been licensed for acute leukemia treatment, including tyrosine kinase inhibitors, BCL2 inhibitors, IDH2 inhibitors, demethylating agents, and monoclonal antibodies including the novel bispecific T-cell engagers (**Table 3**). On the other hand, the latest frontier of cellular therapy relies on the chimeric antigen receptor T-cell therapies (CAR-T), firstly demonstrated to be effective in younger ALL patients [22].

We may certainly expect that further improvements in our understanding of leukemogenesis will lead to later significant success in curing these still terrible diseases.
