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Acute Leukemias

This comprehensive overview discusses Acute Lymphoblastic Leukemia (ALL) and Acute Myeloid Leukemia (AML), focusing on epidemiology, genetics, prognosis, treatment responses, toxicities, and fertility considerations in relation to gender differences.

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Acute Leukemias

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  1. Acute Leukemias

  2. Overview Acute Lymphoblastic Leukemia

  3. ALL is more common in males.2 ALL is the most common childhood cancer2,4 Acute Lymphoblastic Leukemia

  4. Epidemiology Acute Lymphoblastic Leukemia

  5. Maleshave a 20% higher risk of developing ALL2 ALL Epidemiology

  6. ALL Survival Rate

  7. Acute Lymphoblastic Leukemia:1,2,3 • Represents 1/3 of childhood cancer cases • Most common diagnosed childhood cancer Childhood Leukemia Prevalence

  8. Prognosis Acute Lymphoblastic Leukemia

  9. ALL Prognosis 5 year Mortality Rate- girls- 9%, boys-11%2

  10. Males have a relative risk of death - 1.2-1.3x higher than females.2 ALL Treatment Response

  11. Other Considerations Acute Lymphoblastic Leukemia

  12. Higher WBC count is associated with a worse prognosis1,2,3 • Hyperleukocytosis is related to at least one complication during treatment3 • Males may have a higher tendency for a higher WBC4 • Hyperleukocytosis is associated with higher rates of testicular relapse.4 ALL White Blood Cell Count

  13. Sanctuary Site - A part of the body where therapeutic drugs can not reach very well that serves as a possible site of cancer relapse1,2 • ALL Sanctuary Sites:1,2,3 • Testis • Epididymis • Present in 5-8% of ALL • cases without testicular • radiation prophylaxis1,2,3 ALL Sanctuary Site

  14. Males experience a higher loss of bone mineral density1,2,3 • Trabecular (spongy) bone may be the target causing the bone loss1 • Contributing factors:1,3 • Chemotherapy (methotrexate and glucocorticoids) • Decreased nutrition • Vitamin D • Diminished physical activity ALL Bone Density and Lifestyle

  15. ALL and Other Involvement

  16. Genetics Acute Lymphoblastic Leukemia

  17. B-Cell ALL T-Cell ALL ALL Genetics No gender differences have been observed 3,4

  18. Translocation: t(9;22)1,4 Function: Activation of tyrosine kinases causing inhibition of apoptosis and uncontrolled cell growth1,4 Prevalence: More prevalent in adults and elderly1,2 Prognosis: Children (ages 1-9)- better outcomes Adolescence (>9 y/o)- very poor outcomes1,2 No gender differences have been observed3 ALL and Philadelphia Chromosome

  19. Overview Acute Myeloid Leukemia

  20. Acute Myeloid Leukemia, M0 Acute Promyelocytic Leukemia, M3 AML is more common in males.3 Acute Myeloid Leukemia Overview Auer Rods

  21. Epidemiology Acute Myeloid Leukemia

  22. Malesare more commonly diagnosed with AML than females1 AML Epidemiology

  23. Prognostic Factors Acute Myeloid Leukemia

  24. Age, Race, Sex1,3 • Morphology/Immunophenotype1 • Subtypes depending on differentiation and type of cell • Molecular Changes1,2 • NPM1, CEBPA, FLT3 • Cytogenetic markers1,2 • t(8;21), inv16, t(15;17) Prognostic Factors

  25. Males have a higher mortality rate1,3 • 5-year survival rate- 25.9%1 AML Survival Rate

  26. AML and Adolescence

  27. Cytogenetics Acute Myeloid Leukemia

  28. Females have a betterprognosis with t(8;21), inv16, and t(9;22).1 • Femalesare diagnosed more often with t(15;17).2 AML Genetics

  29. Females have a betterprognosis with a normal karyotype.1 • Males have an advantage when diagnosed with t(9;11).1 AML Genetics

  30. Loss of a sex chromosome is associated with t(8;21)2,3 • Loss of X chromosome occurs in 30-40% of females3 • Loss of Y chromosome occurs in 50 % of males3 • Loss of Y chromosome associated with t(8;21) improves the prognosis3 AML and Loss of a Sex Chromosome

  31. Molecular Markers Acute Myeloid Leukemia

  32. Most common molecular marker represented in 30% of AML cases3 NPM1

  33. CEBPA

  34. FLT3

  35. Treatments and Toxicities Acute Leukemias

  36. Pancreatitis1 Neurotoxicity1 Cardiomyopathy1 Graft vs. Host2 Neuropathy1 Osteonecrosis1 Leukopenia2 Treatment Overview

  37. Toxicities

  38. Pathogenesis: Reduced left ventricular wall thickness, cardiac muscle and contractility2,3 Clearance: Lower clearance rates in women5 Sex Bias: Anthracycline induced Cardiomyopathy is more common in females due to fat patterning1,3,4 Treatment: Dexrazoxane provides females more protection1 Long-Term Females are more Effects: likely to develop heart disease1 Anthracycline Induced Cardiomyopathy

  39. Other Toxicities

  40. 6-Mercaptopurine HGPRT enzyme may be responsible for differences in drug metabolism among the sexes5

  41. Sex mismatched hematopoietic cell transplants: • Increased risk of acute and chronic Graft vs. host disease in sex mismatch transplant candidates.1,2 • Decreased survival rate2 • Main incompatibility with male patients receiving a transplant from a female donor1,2 Transplant

  42. Fertility Acute Leukemia

  43. Treatments Linked to Decreased Fertility:1,3,4 • Cyclophosphamide • Testicular Radiation • Cranial Radiation • Fertility Assessment Tests:3 • Semen Analysis • Inhibin B Male Fertility • Cryopreservation should be considered before treatment2

  44. Treatments Linked to Ovarian Failure:1,3 • High dose of alkylating chemotherapy • Radiation near the ovaries • Treatment within 2 years of menarche cause the most ovarian dysfunction3 • Chemotherapy Effects Before Puberty:1,2 • Anovulatory cycles • Decreased ovarian size • Premature ovarian failure/menopause Ovarian Failure

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