Therapeutic advances in leukemia and myelodysplastic syndrome over the past 40 years

Abstract

Major therapeutic progress has been accomplished in leukemia and myelodysplastic syndrome (MDS) over the past 40 years, which may not be fully appreciated by the larger medical community. The objective of this review was to briefly highlight the treatment breakthroughs in leukemia and MDS. Therapeutic progress happened through better understanding of disease pathophysiologies and rational development of targeted agents, like imatinib mesylate in chronic myeloid leukemia (CML), and through astute, empirical discoveries in the clinic, like all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia (APL) and chlorodeoxyadenosine in hairy cell leukemia (HCL). Today, the 5- to 10-year survival rates in patients with APL and HCL exceed 80%. In patients with CML, imatinib therapy has been associated with estimated 5- to 7-year survival rates from 85% to 90%. In patients with adult acute lymphocytic leukemia, modern intensive regimens have improved the 5-year survival rates from 20% up to 40%. In patients with chronic lymphocytic leukemia, chemoimmunotherapy recently produced high rates of quality responses and improved long-term outcome. In younger patients with acute myeloid leukemia (AML), the 5-year survival rates range from 40% to 50%, although elderly AML remains a therapeutic challenge. In patients with MDS, it was recently demonstrated that epigenetic therapy with hypomethylating agents improved survival. Much therapeutic progress has been witnessed in leukemia and MDS, and much more is expected to occur soon.

Figure 1

The survival of patients with acute myeloid leukemia (AML) is illustrated by decade overall (Top), among patients aged <60 years (Middle), and among patients aged ≥60 years (Bottom). Data are from 3766 patients with newly diagnosed AML who were referred to the Leukemia Department of the M. D. Anderson Cancer Center from 1973 to the present.

Figure 2

This chart illustrates the survival of patients with acute promyelocytic leukemia at the M. D. Anderson Cancer Center who received chemotherapy (Chemo), all-trans retinoic acid (ATRA) plus chemotherapy, and ATRA plus arsenic trioxide (AS₂O₃).

Figure 3

Top: The survival of patients with adult acute lymphoblastic leukemia (ALL) is illustrated in this chart from M. D. Anderson Cancer Center data for 3 successive regimens from 1980 to the present: before vincristine, doxorubicin, and dexamethasone (Pre-VAD) (1980–1985); VAD (1985–1992); and hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD) (1992–2007). Bottom: Survival on the HCVAD regimen is illustrated in patients with adult ALL overall and by age group (<50 years vs ≥50 years).

Figure 4

This chart illustrates the survival of patients with chronic myeloid leukemia (CML) before and after imatinib (based on M. D. Anderson Cancer Center data from 1736 patients with newly diagnosed CML who were referred from 1970 to the present). Excluding 11 patients who died from causes other than CML, the estimated 7-year survival rate is 89%.

Figure 5

These charts illustrate the survival of patients (Pts) with chronic lymphocytic leukemia (CLL) by treatment era (Top) and specific regimens (Bottom) from M. D. Anderson Cancer Center (MDA) data. CHOP indicates combined cyclophosphamide, doxorubicin, vincristine, and prednisone; F±P, fludarabine with or without prednisone; FMFC, fludarabine and mitoxan trone/fludarabine and cyclophosphamide; FCR, fludarabine, cyclophosphamide, and rituximab.