Late Effects after Transplantation for Pediatric Severe Aplastic Anemia. Jean E. Sanders, M.D.
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1 Late Effects after Transplantation for Pediatric Severe Aplastic Anemia Jean E. Sanders, M.D.
2 Patient Characteristics Acquired Fanconi Number Gender F:M 63:74 9:6 Etiology: Idiopathic Hepatitis PNH Insecticide Age at Diagnosis Median (range) 10.7 ( ) 6.3 ( ) Years Dx to Tx Median (range) 0.1 ( ) 2.0 ( ) Age at Transplant Median (range) 11.1 ( ) 9.0 ( ) Years Follow-up Median (range) 21.8 (1 38.1) 20 (2-30)
3 Transplant Characteristics First Transplant Regimen S-TBI Fx TBI 12 Gy Fx TBI 2-6 Gy CY + ATG PAPAPACY None Acquired Fanconi 4 11 Second/Third Regimens 15/4 Donor Related Unrelated Syngeneic Acute GVHD 41 (30%) 9 (60%) Chronic GVHD 36 5
4 Survival of Acquired and Fanconi AA Children
5 Late Causes of Death 1-5 years Suicide Chronic GVHD Measles Pneumonia Hemolytic Anemia 5-32 years Pulmonary Failure Malignancy Suicide HIV Hepatitis C Liver Failure Chronic GVHD Acquired Fanconi 2 1 1
6 Mortality Risk Factors Multivariate Analysis Diagnosis Acquired AA Fanconi AA HR (95% CI) (1.4-14) P-value 0.03 Chronic GVHD No Yes ( ) (1.4-10)
7 Survival among AA children with and without chronic GVHD
8 Risk Factors for Chronic GVHD Multivariate Analysis Buffy Coat No Yes Donor Match related Mismatch related Unrelated HR (95% CI) ( ) (2.6-19) 1.98 ( ) P-value
9 Unrelated Donor Transplants N = acquired 15 survive 1-24 years 3 Fanconi 2 survive 5 and 10 years Among the 16 acquired 11 (69%) had chronic GVHD Among the 3 Fanconi 1 died of chronic GVHD
10 Chimerism Not determined for 22 patients transplanted prior to 1976 Among the 130 after that time: 2 were twins 2 (1.5%) had autologous recovery 1 had stable mixed donor/host chimerism 103 had 100% donor chimerism
11 Gonadal Function Acquired AA -- Females Pre-Pubertal Post-Pubertal No. patients Still Pre-pubertal Evaluable Normal develop 30 Abnormal gonad f n -- 1 Early menopause -- 1
12 Gonadal Function Acquired AA -- Males Pre-Pubertal Post-Pubertal Number patients Still pre-pubertal Evaluable Normal develop Abn l gonadotropin 8 9 Low testosterone 0 1
13 Pregnancies after Transplant Regimen CY TBI Gender Female Male* Female Pre-birth Evaluable pregnancies Live Births 58 (82%) 47 (80%) Abortions Birth Defects
14 Growth of Acquired CY AA Children
15 Malignancy Fanconi Patients 2/15 (13%) Fanconi patients developed malignancy 9 and 12 years post-tx 1 developed adenocarcinoma of the colon and is surviving 1 developed metastatic squamous carcinoma which was cause of death
16 Malignancy Acquired AA patients 19/137 (13%) developed malignancy 1-31 years after transplant. 3 thyroid malignancy all survive 1 PNH developed MDS second tx 1 developed melanoma successful treated 7 developed squamous cell carcinoma which was cause of death for 1 3 developed breast cancer which was the cause of death for 1 1 patient died of metastatic cervical cancer 2 hepatocarcinoma assoc. with Hepatitis C 1 survives after liver transplant and 1 died
17 Hepatitis C disease 104 children transplanted prior to 1992 and 37 (35%) are known to be Hepatitis C positive. Among the 31 surviving with Hep C 1 required a liver transplant 12 were treated with ribavirin and/or interferon 5 no longer Hep C + 7 failed and 1 received a liver transplant 18 remain untreated
18 Quality of Life Formal QOL data available for 49 adult survivors of this pediatric AA transplant. SF-36 physical function and mental function studies among survivors and controls were not different from each other Also not different from controls was educational status, work or school status, financial situation or marital status. In contrast, insurance issues were significantly different for the transplant recipients for both health and life insurance.
19 Summary Marrow transplantation offers effective therapy for children with severe AA Majority who survive beyond one year after transplant grow up to become normal functioning adults. The children grow up and have normal children of their own. Overall, these former patients are doing very well.
20 INFANT ACUTE LEUEKMIA LATE EFFECTS Jean E. Sanders, MD Fred Hutchinson Cancer Research Center and the University of Washington School of Medicine
21 Infant ALL Population Number patients 25 Survival 23 Cause of Death 2 Relapse Time post HCT Age last follow-up 9.3 (1.8-21) yrs 10.5 ( ) yrs
22 Infant AML Population Number patients 9 Survival 6 Cause of Death Relapse 1 Secondary malignancy 1 Chronic GVHD 1 Time post HCT 18 (1-25) yrs Age last follow-up 20 ( ) yr
23 Infant Transplant Regimens Chemotherapy plus TBI 29 Busulfan + Cytoxan 5
24 Secondary Malignancies Number patients 3 Astrocytoma 1 fatal Thyroid (papillary) 1 alive Nerve Sheath tumor 1 alive
25 Cognitive Evaluations I Q Development School Performance
26 I Q Studies Number Studied 12 FSIQ 103 (66-119) PIQ 108 (63-120) VIQ 100 (75-126)
27 Development (subjective) Number patients 30 Normal 10 Speech delay 18 Motor delay 2 Catch-up speech/motor 20
28 School Performance Number evaluable 19 No problems noted 9 Special education 7 ADHD 3 Comments: A student Enjoys School Starting college Needs help Memory issue
29 Pulmonary Function Number Evaluable 20 Normal Function 17 Restrictive Lung Dz 3
30 Cardiac Studies Number patients 13 Normal Echocardiogram 9 Valve insufficiency 3
31 Dental Issues Number evaluated 15 Normal examination 2 Abnormal exam 13 Small jaw 5 Small palate 3 Missing teeth 5 Short roots 8
32 Endocrine Issues Growth Puberty Thyroid
33 Growth Growth Hormone evaluation 25 patients GH deficiency 17 pts (68%) GH therapy 10 pts Growth Z-scores -1.5 (-5.7 to +0.6)
34 BUCY 1 14 STANDARD DEVIATION CENTIMETERS / YEAR PRE YEARS POST TRANSPLANT YEARS OF AGE BOYS (N=18) GIRLS (N=18)
35 Puberty Evaluable patients 12 Normal development 7 Delayed development 3 Precocious puberty 3
36 Thyroid Function Number patients tested 18 Normal 2 CHT 11 Hypothyroid 2 Thyroiditis 1 Malignancy 2 - both Rx
37 Thyroid dysfunction by BMT age
38 Thyroid dysfunction by regimen
39 Conclusions Infants have the same problems after transplant as older transplanted children. Cognitive function is satisfactory even after TBI regimens. Development is delayed during the first year, but catch-up occurs. Dental issues must be followed. Endocrine problems may occur which need to be treated.
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