PSYCHIATRIC SEQUELAE IN SERIOUSLY ILL CHILDREN AND THEIR FAMILIES

CONSULTATION-LIAISON PSYCHIATRY

0193-953X/96 $0.00

+

.20

PSYCHIATRIC SEQUELAE IN SERIOUSLY ILL CHILDREN AND THEIR FAMILIES Margaret L. Stuber, MD

Recent advances in the treatment of pediatric illnesses have transformed a number of previously fatal conditions to life-threatening but potentially survivable conditions. The new intensive regimens, however, although offering the chance of prolonged or permanent remission of the underlying disease, are also problematic. The technology and intensity of treatment can itself be highly stressful, even traumatic, both physically and psychologically for children and their parents. Survivors and their families may be left with long-term medical and psychiatric sequelae. Those who are fortunate enough to survive the initial illness may have exchanged a life-threatening illness for a chronic condition. For example, pediatric acute lymphocytic leukemia, generally fatal within months only a few decades ago, now can be treated with intensive chemotherapy and radiation resulting in a long-term survival of approximately 65%.' The treatment, however, involves multiple and often prolonged hospital stays; painful procedures, such as bone marrow aspirations; and months of outpatient chemotherapy. Many children require courses of daily cranial irradiation, which are usually frightening for the child, who must be separated from parents for the treatment. Parents must often take prolonged leaves of absence or quit jobs to care for the child, who is vulnerable to deadly infection or bleeding. Even This work was supported by a Clinical Mental Health Academic Award (grant K07M401604) from the National Institute of Mental Health.

From the Division of Child and Adolescent Psychiatry, University of California Los Angeles School of Medicine, Los Angeles, California

THE PSYCHIATRIC CLINICS OF NORTH AMERICA

-

VOLUME 19 NUMBER 3 * SEPTEMBER 1996

481

482

STUBER

after the treatment is complete, later complications, often called late effects, may emerge. The chemotherapy puts children at higher risk of other malignancies in future years,17,35 and the cranial irradiation adds the probability of learning disabilities and a drop in overall intelligence.12,40

Similar issues are raised by organ transplantation, another lifesaving procedure recently made available to children with end-stage kidney, heart, and liver disease. Although these children have a very high chance of survival after successful tran~plantation,2~ they must continue on immunosuppressive drugs for the rest of their lives, putting them at risk for other malignancies.26Even if the new organ is performing well, survivors face the chronic problems of multiple daily medications, medical follow up, and added vulnerability to illness. Thus, the psychiatric impact of serious pediatric illness includes not only acute responses to life threat and treatment, but the psychiatric implications of the chronic difficulties and ongoing interventions that are the cost of survivorship for many conditions. Although the child is generally the most obvious focus of the various stressors, the child’s family may be equally or even more affected in the long term. This article reviews what is known of the psychiatric sequelae in survivors of life-saving pediatric interventions for serious medical illnesses and their families. The relative contributions of the underlying illness and the intensive treatments that are now commonly used are examined. Potential mediators of later psychiatric complications are discussed. Finally, interventions, both for prevention and treatment, are suggested based on the current state of knowledge. Childhood cancer and organ transplantation are used as the primary examples throughout, because these represent areas of recent dramatic technical advance. TYPES OF PSYCHIATRIC SEQUELAE

Given the stressors listed previously, there has been considerable clinical concern about the emotional consequences for survivors and families who have been through serious pediatric illnesses. Koocher and O ’ M a l l e ~referred ~~ to childhood cancer survivors and their families as suffering from the Damocles’ syndrome, in reference to the ongoing threat with which they lived. Early epidemiologic studies found a significantly higher rate of psychological adjustment difficulties among children with physical disorders than among healthy children.47A number of subsequent studies examining the adjustment of survivors, however, have found that the overall level of functioning is not significantly different than that of healthy comparison groups. In a phone interview study of 95 adult survivors of pediatric cancer, the survivors appeared to be functioning normally in the areas of educational achievement, occupational status, interpersonal relationships, marital status, pregnancies, employee benefits and insurance, and medical and health behavi o r ~Similarly, .~~ a study of 219 childhood cancer survivors now in their

PSYCHIATRIC SEQUELAE IN SERIOUSLY ILL CHILDREN AND THEIR FAMILIES

483

third and fourth decades found survivors to be comparable with controls in the areas of education, employment, and insurance.lSStudies of pediatric organ transplant recipients have also found good adjustment in long-term survivor^.^ Other studies, however, have suggested that a subgroup of survivors does have significant problems. For example, Koocher and O'Malley's2' classic investigation of pediatric oncology survivors found that, although 53% of the 117 survivors studied appeared well-adjusted, 11%had severe to disabling problems. Problems with self-esteem, depression, anxiety, peer relationships, and school and work were common. A later study of 41 adolescent survivors found good or excellent global functioning in 6l%, with depression reported rarely, and selfconcept scores higher than normative values. Concerns about their bodies, however, were reported by over half of the group, with 27% rated as counterphobic and 26% as hypo~hondriacal.'~ Problems noted in other studies have included despair, hopelessness and somatic complaint^,"^ deficits in social c0mpetence,3~behavioral difficulties,", 37 and increased difficulty with school perf~rmance.~' Pediatric cancer survivors have reported persistent illness-related concerns, negative body image, and 33, 37 somatic preoccupation.lO, Not all changes after serious illness are viewed as being negative. Sixty percent of the adolescents in the Fritz et a1 study14 identified a positive effect of the illness. A study of more than 300 childhood cancer survivors aged 14 to 29 found that survivors reported feeling more positive than their peers, with fewer general health concerns; however, they continued to have worries about cancer-related illnesses and reported more negative health status than their peers.32Cancer survivors were found to have significantly fewer depressive symptoms than controls in a study that also found that survivors were more likely to report low anxiety and high defensiveness.'O This is consistent with a repressive 69 coping style or the use of denial to deal with ongoing difficultie~.~~. Behavioral and emotional difficulties appeared to improve with time,"', although school difficulties persisted.s1 Families are also affected by a child's serious illness. Although some studies of families of chronically ill patients have found them to respond with increased cohesion,16 a study of 88 adolescent cancer survivors found that survivors reported lower levels of family cohesion than a control group of healthy adolescent^.^' The experience of serious illness may change the overall development of the family, requiring change and 43 adaptation that most but not all families are able to accommodate.21* Although the data on siblings is contradictory and beset by methodologic difficulties, it is clear that serious illness in a sibling is stressful and can result in negative behavioral change and distress during treatment.8 A study of 254 siblings of pediatric cancer patients found that siblings reported distress about the lack of attention to their needs, the separations and disruptions in the family, the impact of cancer treatment, and their fear of death. They also indicated, however, that they felt they were more compassionate and that their families were closer

484

STUBER

as a result of the e ~ p e r i e n c eSiblings .~~ who have been directly involved in the care of the ill child, such as bone marrow or solid-organ donors, appear to be emotionally affected by the experience. Donor’s adverse responses seem to be at least partially dependent on the medical outcome of the ill sibling.@ More is known about the parents of seriously ill children and adolescents. A descriptive study of 37 parents of childhood cancer survivors found that the parents reported pervasive concerns about their children’s future health and the possibility of relapse.3o In addition to the many studies of anxiety, depression, and overall adaptation done with pediatric survivors and their families, recently investigators have begun to explore the possibility of posttraumatic stress. Early observers of serious illness in children noted that survivors resembled people who had been traumatized, like war veterans.39,31 Recent studies have specifically investigated the presence of symptoms of posttraumatic stress in childhood cancer survivors and their parents.44,48, 57, Although there is some evidence that some survivors are reporting trauma symptoms years after the end of successful treatment, parents are much more affected, reporting significantly more symptoms than control parents.20 @

CAUSES OF PSYCHIATRIC SEQUELAE

As mentioned previously, there are a number of potential sources of stress when a child has a serious medical illness. One is the diagnosis itself and the fears that it raises. The American Psychiatric Association has recently recognized the highly stressful nature of a potentially fatal illness by adding ”learning that one/one’s child has a life-threatening illness” to the list of stressors considered capable of precipitating posttraumatic stress disorder in their Diagnostic and Statistical Manual-IV (DSM-IV).’ Prior to this, chronic illness was specifically mentioned as not meeting this criterion. In addition to the diagnosis, the treatment is a potential stressor. Saylor et a1,5* assessing depression and anxiety among 39 hospitalized pediatric patients, found that the most consistently significant predictor of psychological distress was the number of physical stressors, such as placement of intravenous lines. Because successful treatment of many serious childhood illnesses requires intensive and painful, intrusive treatment, these interventions may be a source of psychiatric morbidity. Alternatively, it may be the consequences of the treatment that may be the greater stressor. As mentioned previously, the aggressive procedures now done to treat serious childhood illness are not only intrusive and painful, but they can have long-term adverse medical sequelae. Interestingly, visible physical impairment was not found to predict psychosocial adjustment in a group of 116 childhood cancer s ~ r v i v o r sFunctional .~~ impairment as a result of disease and treatment for childhood cancer, however, increased the risk of maladjustment from

PSYCHIATRIC SEQUELAE IN SERIOUSLY ILL CHILDREN AND THEIR FAMILIES

485

twofold to fourfold in a study of 183 survivors. School-related problems were significantly increased for those who had undergone cranial radiation as part of the treatment.37Similarly, Kazak and Meadowszzfound that children who had brain damage secondary to treatment demonstrated more adjustment difficulties. Although childhood brain-tumor survivors appeared to have more inhibition of activities and school performance than other cancer survivors, however, they did not demonstrate any more evidence of psychopathology.’l Several recent studies have underscored the importance of the perception of the stressor in determining the responses. There is some evidence that the procedures and treatment may be perceived as more traumatic than the actual life threat posed by the illness, particularly for younger children.60* Commonly used objective or data-based assessments of treatment intensity or even statistical predictions of life threat are not predictive of posttraumatic stress symptoms in childhood cancer survivors59;however, the survivors’ appraisal of the stressor predicts psychosocial a d j ~ s t m e n tAppraisal .~~ of treatment intensity by the child survivor or parent is a strong predictor of that individual’s posttraumatic stress.61There also appears to be an interaction between the distress reported by a survivor’s mother and the appraisal of intensity of treatment made by the This is of potential importance not only for intervention with parents, but because children and parents otherwise appear to be responding to somewhat different aspects of the diagnosis and treatment.59 Other potential sources of psychiatric problems are the medical consequences of the illness and treatment. Visible deformities, such as scarring after burns and amputations for malignancies, although perhaps the most obvious, have not proved to be the primary source of psychiat42 Cranial irradiation for leukemia or brain tumors may ric diffi~ulty.~~, leave an invisible but functionally significant mark, resulting in a range of impairments including learning disorders and mild to moderate decreases in intelligence, depending on the amount of radiation used.’2,67 There is evidence that children who have sustained such brain damage are more vulnerable to psychological problems than other survivors who do not have neuropsychologic sequelae.zz Serious illness in childhood can alter the normal developmental trajectory of a child or adolescent. Missed days of school, isolation from peers, or temporary disfigurement is disruptive to the developing sense of identity, as well as development of cognitive and social skills during the acute phase of the illness. Even after the child is generally well and back in usual activities, ongoing treatment, such as the immunosuppressives taken by transplant recipients, or the insulin injections of diabetics, can be experienced as stigmatizing by children and especially by adolesc e n t ~The . ~ ~medications may also cause side effects that are experienced as aversive, such as weight gain. Survivors may respond with avoidance, resulting in nonadherence with medical advice and more acute medical problems.55 Beliefs and prejudices in the community about specific conditions

486

STUBER

can also adversely effect survivors. Stories of the lengths to which people have gone to keep human immunodeficiency virus-infected children out of schools are well known, but in the early days of organ transplantation schools were also reluctant to have transplant survivors return to school, fearful of medical sequelae. Adolescent cancer survivors prefer to keep their experience a secret from friends and teachers, fearful of being seen as different from their peers.58Adult survivors of pediatric cancer have been refused entry into the uniformed services, often face difficulties in getting life insurance in the early years off treatment, and may be less likely to marry or marry later.I9 Family members may also experience far ranging consequences of their involvement in the child’s illness and treatment. Anxiety, guilt, helplessness, or emotional over-involvement with the child during the acute phase of the illness can have long-term effects on the parental marriage or on the development of a sibling. This is particularly profound in cases where the family member is an active contributor to the treatment, such as organ donors,68 or when the illness is genetic or secondary to treatment, such as lymphoproliferative disease after immunosuppression for organ transplantation. The recent introduction of the potential for family members to donate not only kidneys but parts of their livers for children with end-stage organ failure has created new and unique situations for families.15These new high-technology interventions raise ethical concerns and present perplexing choices for families.53 Concrete consequences of the illness, or secondary adversities, may also present persistent problems. These include need for the family to live on one income rather than two, or payment of medical bills, which limit the activities or social options of the family. Families may choose to remain at jobs that maintain their medical insurance, because they are otherwise limited by ”pre-existing condition” clauses. Such difficulties may become more or less frequent in the future, depending on the evolution of health service delivery systems and their financing. MEDIATING FACTORS

Understanding why certain children and their parents develop symptoms, whereas others exposed to the same event do not, has been of interest to many researchers. There appear to be two types of mediators: (1) those internal to the individual, and (2) those that are external. Internal factors include not only epidemiologic variables, such as age, gender, and ethnicity, but also the child’s characteristic ways of interpreting or responding to potentially stressful events. Age is known to be an important determinant of the responses of children to a variety of events. Younger children, who are less cognitively sophisticated in their understanding of death, do not respond to life threat in the same way as older children.26When adolescents were asked about their understanding of having undergone a bone marrow transplantation for cancer as children, many stated that they had not understood that their lives

PSYCHIATRIC SEQUELAE IN SERIOUSLY ILL CHILDREN AND THEIR FAMILIES

487

were in danger until some time after the transplant.62The relative importance of life threat and treatment intensity appears to vary with age, with younger children putting more of an emphasis on painful or frightening procedure^.^^ Current age appears to be less important than age at diagnosis and treatment. It is extremely difficult, however, to assess children below the age of 7 years adequately given our present assessment Gender and time since treatment ended are less significant predictors than might be expected,'" although some types of adjustment do appear to improve over time.", 51 Siblings' responses also appear to be influenced by age. Older siblings were more likely than younger siblings to report positive effects of having a child with cancer in the family in a study of 254 siblings, ages 5 to 18 years.50 A child's understanding of the meaning of death, and therefore of life threat, normally varies significantly with the age of the child. Koocherz6,27 found that the Piagetian framework of cognitive development provides a reasonable explanation of the progression of the way a child thinks about death. Preschool age children, in the preoperational or prelogical phase of thinking, are unlikely to see death as permanent, and have a magical sense of things coming back to life. As children progress to the concrete operational thinking of school age, they are more able to understand the permanence of death and begin to understand that death can be a consequence of serious injury or illness. Only in adolescence, when abstract thinking is obtained, is death understood in the ways that adults comprehend it. In addition to ability to understand, the interpretation of the event is influenced by age. Adolescents, who are developmentally working on separation and independence are very stressed by the dependence and lack of control inherent in the patient role.13Serious illness and treatment have a profound impact on the adolescents' diet, activities, and schedule at a time when these aspects of their lives are generally being hotly debated by the teens and their parents or are finally coming under the adolescents' control. Nonadherance to treatment recommendations, despite knowledge of the potential consequences, is common among adolescents. Some studies have found, however, that adolescents report not only enhanced closeness in the family but also increased perceptions of mastery.56 Psychological characteristics also influence the experience and sequelae of serious illness. Among these may be the individual's trait anxiety, which includes baseline anxiety as well as the predisposition to respond to events with anxiety. In a comparison of cancer survivors and their parents to controls, trait anxiety was strongly correlated with symptoms of post-traumatic stress for survivors, mothers, and fathers, although anxiety was not significantly different between subjects and controls.22Such anxiety appears to contribute to the appraisal of the stressful event, which, as discussed previously, appears to be a major contributor to a distressed response. Coping style also influences the symptoms seen or reported by survivors and their families. Repression or denial has been noted by several researchers as a common coping

488

STUBER

style for childhood cancer patients, resulting in the apparent absence of depressed or anxious symptoms.10,46, 69 The match between the events and the coping approach, however, may also be important, with active management of emotional response most helpful in situations in which the threat was unavoidable, such as most aspects of treatment.66 The external factors that appear to mediate the impact of the illness include social support and family factors. In a study of adolescent survivors of serious burns, Orr4zfound that perceived social support was the only significant predictor of emotional sequelae, more powerful than size or location of the burn. Social support also appears to be an important mediator for family members of children with physical disabilities4 and cancer survivors.z2There is some evidence that the family’s ability to accommodate to the changing needs of an ill family member may be a major predictor of long-term adjustmentzzor even the medical survival of the ill family member.16 A largely unexplored area is the impact of culture and ethnicity on the psychiatric sequelae of medical events. Some initial investigations have suggested that there are significant differences in the way children of various backgrounds respond to painful procedures45or their distress during treatment.70The high priority traditionally accorded patient autonomy in western medicine is also not universally embraced by some other cultures, who prefer to use the family as the focus for communication and support regarding their illnesses6 Because most of the results reported in this article are from studies on citizens of the United States who are of European heritage, it cannot be assumed that generalizations can be made to diverse children and families. For example, cultures that do not put so high a value on independence may be less concerned by the patient role and more upset by the impact on the family or community of an illness. INTERVENTIONS

Given what is known about the precipitating and mediating factors, it seems that the best intervention for reducing long-term sequelae of serious medical illness for both child and family is to decrease the acute stressors at the time of diagnosis and treatment. Unfortunately, at present the primary means of decreasing the life threat posed by a disease is to increase the intensity of the treatment. Because perception of intensity or life threat appears to be more critical than objectively measurable ”reality,” however, it may be possible to decrease the perceived treatment intensity even if the actual number of procedures cannot be safely reduced. A number of studies have found that psychological preparation, such as hypnosis or cognitive-behavioral intervention, is useful as an adjunct to pharmacologic interventions in decreasing anxi23, 34, 71 It is not ety, helplessness, and distress during painful proced~res.’~, yet known whether such interventions can prevent long-term emotional distress.

PSYCHIATRIC SEQUELAE IN SERIOUSLY ILL CHILDREN AND THEIR FAMILIES

489

It should be noted that interventions to reduce the distress of children and parents about a serious diagnosis or intensive treatment do not attempt to hide the actual life threat posed by the underlying illness nor the nature of any intrusive treatment. This is not legal in the United States, nor is it considered ethical, because people cannot give informed consent for treatment without information about possible consequences. There are also data that open communication with children about life-threatening situations results in less emotional distress than protecting them from difficult Some cultures, however, continue to believe that it is destructive to “take away a person’s hope” by telling them that they have a potentially fatal illness.6 Analyses of the impact of treatment on quality of life and a growing understanding of children’s pain have resulted in alterations in the treatment protocols for some illnesses. Until relatively recently it was assumed that children did not feel pain in the same way that adults do, and analgesics were rarely prescribed for ~hildren.~’ Now it is appreciated that it is the expression of pain rather than the distress that differs in children. Pediatric cancer protocols have been modified to decrease the number of invasive, painful procedures, such as bone marrow aspirations. More effective medications have been found for the nausea associated with chemotherapy and for the topical anesthetic used for placing intravenous lines. Protective isolation for immunosuppressed patients has been modified, sparing bone marrow and other organ transplant patients from prolonged separations from loved ones. Treatment has also been modified with an eye to long-term medical sequelae and resultant psychiatric complications. For example, the neuropsychological consequences of high-dose cranial radiation have significantly influenced cancer treatment research, as oncologists seek combinations of treatments that effectively eradicate central nervous system involvement in leukemia with the minimum impact on brain functioning40 Little intervention research has been done with survivors and their parents and siblings. Ostroff and S t e i n g l a ~ sargue ~ ~ that such interventions should be family-focused and propose a model of the multiple family group. A major goal of such intervention is to help the family to return to a normal developmental trajectory, rather than remaining organized around the illness. Successful group work with adolescents is challenging, given their reluctance to identify with the illness to that extent. Parents are, however, often eager to have the type of support provided by a group and can sometimes persuade their adolescents to parti~ipate.~~ SUMMARY

Going through a life-threatening illness as a child or adolescent is a tremendously stressful experience for the entire family. Although the majority of survivors do go on to adjust and function well, some have

490

STUBER

ongoing problems. These problems include evidence of posttraumatic stress, learning difficulties, depression, and anxiety. Their parents appear to be even more severely affected, possibly because they had a better appreciation at the time of the true dangers posed by the illness and the treatment. Little is yet known about their siblings, although it is clear that the acute stage of illness and treatment effects the entire family. Areas needing study include the long-term sequelae on siblings of survivors, as well as a better understanding of the precipitants and mediators of the problems noted in survivors and parents. Only then can interventions and preventative measures be undertaken and tested. Also needed is a better understanding of the impact of cultural differences on precipitants, mediators, and symptoms.

References 1. American Cancer Society: Cancer Facts and Figures. Atlanta, American Cancer Society, 1994 2. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 4. Washington, DC, American Psychiatric Association, 1994 3. Bailey LL, Gundry SR, Razzouk AJ, et al: Bless the babies: One hundred fifteen late survivors of heart transplantation during the first year of life. J Thorac Cardiovasc Surg 105:805-815, 1993 4. Barakat L, Linney JA: Children with physical handicaps and their mothers: The interrelation of social support, maternal adjustment, and child adjustment. J Pediatr Psycho1 17725-739, 1993 5. Bennett D: Depression among children with chronic medical problems: A meta-analysis. J Pediatr Psycho1 19:149-170, 1994 6. Blackhall LJ, Murphy ST, Frank G, et al: Ethnicity and attitudes toward patient autonomy. JAMA 274:820-825, 1995 7. Bleyer WA: Acute lymphoblastic leukemia in children. Advances and prospectus. Cancer 65 (suppl 3):689-695, 1990 8. Breyer J, Kunin H, Kalish LA, Patenaude A F The adjustment of siblings of pediatric cancer patients-a siblings and parent perspective. PsychoOncology 2:201-208, 1993 9. Brown R, Kaslow N, Hazzard A, et al: Psychiatric and family functioning in children with leukemia and their parents. J Am Acad Child Adolesc Psychiatry 31:495-502,1992 10. Canning EH, Canning RD, Boyce WT: Depressive symptoms and adaptive style in children with cancer. J Am Acad Child Adolesc Psychiatry 31:1120-1124, 1992 11. Carpentieri SC, Mulhern RK, Douglas S, et al: Behavioral resiliency among children surviving brain tumors: a longitudinal study. Journal of Clinical Child Psychology, 22:236-246, 1993 12. Copeland DR Neuropsychological and psychosocial effects of childhood leukemia and its treatment. CA Cancer J Clin 42:283-295, 1992 13. Eiser C: Growing Up With a Chronic Disease: The Impact on Children and Their Families. London, Jessica Kingsley Publishers, 1993 14. Fritz G, Williams J, Amylon M: After treatment ends: Psychosocial sequelae in pediatric cancer survivors. Am J Orthopsychiatry 58:552-561, 1988 15. Goldman LS Liver transplantation using living donors: Preliminary donor psychiatric outcomes. Psychosomatics 34:235-240, 1993 16. Gonzalez S, Steinglass P, Reiss D: Putting the illness in its place: Discussion groups for families with chronic medical illnesses. Fam Process 28:69-87, 1989 17. Green DM: Effects of treatment for childhood cancer on vital organ systems, Cancer 10:3299-3305, 1993 18. Hays DM, Landsverk J, Sallon SE, et al: Educational, occupational, and insurance

PSYCHIATRIC SEQUELAE IN SERIOUSLY ILL CHILDREN AND THEIR FAMILIES

491

status of childhood cancer survivors in their fourth and fifth decades of life. J Clin Oncol 10:1397-1406, 1992 19. Jay S, Elliott C, Katz E, Siege1 S: Cognitive-behavioral and pharmacological interventions for children’s distress during painful medical procedures. J Consult Clin Psychol 55~860-865, 1987 20. Kazak A, Barakat L, Meeske K, et al: Post traumatic stress, family functioning, and social support in survivors of childhood leukemia and their mothers and fathers. J Consult Clin Psychol, in press 21. Kazak A, Christakis D, Alderfer M, Coiro MJ: Young adolescent cancer survivors and their parents: Adjustment, learning problems, and gender. Journal of Family Psychology 8174-84, 1994 22. Kazak A, Meadows A: Families of young adolescents who have survived cancer: Social-emotional adjustment, adaptability, and social support. J Pediatr Psychol 14:175191, 1989 23. Kazak A, Penati B, Boyer B, et al: A randomized controlled prospective outcome study for a psychological and pharmacological intervention protocol for procedural distress in pediatric leukemia. J Pediatr Psychol, in press 24. Klintmalm GB, Husberg BS, Starzl TE: The organ transplanted patient-immunological concepts and immunosuppression. In Makowka L (ed): The Handbook of Transplantation Management. Austin, TX, R. G. Landes Co, 1991, pp 72-108 25. Kocoshis SA, Tzakis AG, Todo S, et al: Pediatric liver transplantation: History, recent innovations, and outlook for the future. Clin Pediatr 32:386-392, 1993 26. Koocher GP: Childhood, death, and cognitive development. Developmental Psychology 9:369, 1973 27. Koocher GI? Talking with children about death. Am J Orthopsychiatry 44:404, 1974 28. Koocher GP, MacDonald BL: Preventive intervention and family coping with a child’s life-threatening or terminal illness. In Akamatsu TJ, Parris MA (eds): Family Health Psychology. Series in Applied Psychology: Social Issues and Questions. Washington, DC, Hemisphere, 1992, pp 67-86 29. Koocher J, OMalley J: The Damocles Syndrome. New York, McGraw-Hill, 1981 30. Leventhal-Belfer L, Bakker AM, Russo C: Parents of childhood cancer survivors: A descriptive look at their concerns and needs. Journal of Psychosocial Oncology, 11:1942, 1993 31. Levy DM: Psychic trauma of operations in children. American Journal of Diseases of Children 69:7-25, 1945 32. Lozowski SL: Views of childhood cancer survivors: Selected perspectives. Cancer 71:3354-3357, 1993 33. Madan-Swain A, Brown RT: Cognitive and psychosocial sequelae for children with acute lymphoblastic leukemia. Clinical Psychology Review 11:267-294, 1991 34. Manne SL, Bakeman R, Jacobson PB, et al: Adult-child interaction during invasive medical procedures. Health Psychol 11:241-249, 1992 35. Meadows AT, Hobbie W: The medical consequences of cure. Cancer 58:524-528, 1986 36. Meadows AT, McKee L, Kazak AE: Psychosocial status of young adult survivors of childhood cancer: A survey. Med Pediatr Oncol 17:466470, 1989 37. Mulhern RK, Wasserman AL, Friedman AG, Fairclough D Social competence and behavioral adjustment of children who are long-term survivors of cancer. Pediatrics 83~18-25, 1989 38. Nader K, Stuber M, Pynoos R: Posttraumatic stress reactions in preschool children with catastrophic illness: Assessment needs. Comprehensive Mental Health Care 1:223239, 1991 39. Nir Y: Post-traumatic stress disorder in children with cancer. In Eth S, Pynoos RS (eds): Posttraumatic Stress Disorders in Children. Washington, DC, American Psychiatric Press, 1985, pp 123-132 40. Ochs J, Mulhern R, Fairclough D, et al: Comparison of neuropsychological functioning and clinical indicators of neurotoxicity in long-term survivors of childhood leukemia given cranial radiation or parenteral methotrexate: A prospective study. J Clin Oncol 9:145-151, 1991

492

STUBER

41. OMalley JE, Foster D, Koocher G, Slavin L: Visible physical impairment and psychological adjustment among pediatric cancer survivors. Am J Psychiatry 13794-96, 1980 42. Orr DA, Resnikoff M, Sity GM: Body image, self-esteem, and depression in burninjured adolescents and young adults. J Bum Care Rehabil 10454461, 1989 43. Ostroff J, Steinglass P: Psychosocial adaptation following treatment: A family systems perspective on childhood cancer survivorship. In Baider L, Copper CL, Kaplan DeNour A (eds): Cancer and the Family. New York, John Wiley & Sons, 1995 44. Pelcovitz D, Kaplan S Disorders of extreme stress and PTSD in cancer survivors. Presented at the Annual Meeting of the International Society for Traumatic Stress Studies. Los Angeles, November, 1992 45. Pfefferbaum B, Adams J, Aceves J: The influence of culture on pain in anglo and hispanic children with cancer. J Am Acad Child Adolesc Psychiatry 29:642-647, 1990 46. Phipps S, Fairclough D, Mulhern RK: Avoidant coping in children with cancer. J Pediatr Psychol 20:217-232, 1995 47. Pless IB, Roghmann KJ: Chronic illness and its consequences: Observations based on three epidemiological studies. J Pediatr 79:351-359, 1971 48. Pot-Mees CC: The Psychosocial Effects of Bone Marrow Transplantation in Children. Delft, Eburon Publishers, 1989 49. Rait DS, Ostroff JS, Smith K, et al: Lives in a balance: Perceived family functioning and the psychosocial adjustment of adolescent cancer survivors. Fam Process 31:383397, 1992 50. Sargent JR, Sahler OJZ, Roughmann KJ, et al: Sibling adaptation to childhood cancer collaborative study: Siblings perceptions of the cancer experience. J Pediatr Psychol 20~151-164,1995 51. Sawyer MG, Rice M, Haskell C, et al: School performance and psychological adjustment of children treated for leukemia at long term follow-up. The American Journal of Pediatric Hematology/Oncology 11:146-152, 1989 52. Saylor CF, Pallmeyer TI', Finch AJ, et al: Predictors of psychological distress in hospitalized pediatric patients. J Am Acad Child Adolesc Psychiatry 26:232-236, 1987 53. Sexson S, Rubenow J: Transplants in children and adolescents. In Craven J, Rodin GM (eds): Psychiatric Aspects of Organ Transplantation. Oxford, Oxford University Press, 1992, pp 33-49 54. Singer PA, Siegler M, Whittington PF, et al: Ethics of liver transplantation with living donors. N Engl J Med 321:620-622, 1989 55. Slater JA: Psychiatric aspects of organ transplantation in children and adolescents. Child and Adolescent Psychiatric Clinics of North America 3:557-598, 1994 56. Smith K, Ostroff J, Tan C, et al: Alterations in self-perceptions among adolescent cancer survivors. Cancer Invest 9:581-588, 1991 57. Stuber M, Christakis D, Housekamp B, et al: Post trauma symptoms in childhood leukemia survivors and their parents. Psychosomatics 37254-261, 1996 58. Stuber ML, Gonzalez S, Benjamin H, et al: Fighting for recovery: Group interventions for adolescents with cancer and their parents. The Journal of Psychotherapy Practice and Research 4:286-296, 1996 59. Stuber ML, Gonzalez S, Meeske K, et al: Post traumatic stress after childhood cancer 11: A family model. Psychooncology 3:313-319, 1994 60. Stuber ML, Kazak A, Meeske K, et al: Posttraumatic stress in survivors of childhood leukemia and their parents. Presented at the Annual Meeting of the American Academy of Child and Adolescent Psychiatry. New Orleans, October 1995 61. Stuber ML, Meeske K, Gonzalez S, et al: Post-traumatic stress in childhood cancer survivors I: The role of appraisal. Psychooncology 3:305-312, 1994 62. Stuber ML, Nader K O Psychiatric sequelae in adolescent bone marrow transplantation survivors: Implications for psychotherapy. The Journal of Psychotherapy Practice and Research 4:30-42, 1995 63. Stuber ML, Nader KO, Pynoos RS: Appraisal of life threat and acute trauma responses in childhood bone marrow patients. J Trauma Stress, in press 64. Stuber ML, Nader K, Yasuda P, et al: Stress responses after pediatric bone marrow transplantation: Preliminary results of a prospective, longitudinal study. J Am Acad Child Adolesc Psychiatry 50:407-414, 1991

PSYCHIATRIC SEQUELAE IN SERIOUSLY ILL CHILDREN AND THEIR FAMILIES

493

65. Varni JW, Katz ER, Colegrove R, et al: Perceived stress and adjustment of long-term survivors of childhood cancer. Journal of Psychosocial Oncology 12:l-16, 1994 66. Weisz JR, McCabe MA, Dennig M D Primary and secondary control among children undergoing medical procedures: Adjustment as a function of coping style. J Consult Clin Psycho1 62:324-332, 1994 67. Williams JM, Davis KS: Central nervous system treatment for childhood leukemia: Neuropsychological outcome studies. Cancer Treat Rev 13113-127,1986 68. Wolcott D, Wellisch D, Fawzy F, Landsverk J: Psychological adjustment of adult bone marrow transplant donors whose recipient survives. Transplantation 41:484-488, 1986 69. Worchel FF, Rae WA, Olson TK, Crowley SL: Selective responsiveness of chronically ill children to assessment of depression. J Pers Assess 59:605-615, 1992 70. Zeltzer L, LeBaron S Does ethnicity constitute a risk factor in the psychological distress of adolescents with cancer? J Adolesc Health 6:8-11, 1985 71. Zeltzer L, LeBaron S Hypnosis and nonhypnotic techniques for reduction of pain and anxiety during painful procedures in children and adolescents with cancer. J Pediatr 97132-138, 1982

Address reprint requests to Margaret L. Stuber, MD 760 Westwood Plaza Room 48-240 A Los Angeles, CA 90024-1759