Case study 1
A 26-Year-Old Man With History of Fatigue, Fevers, and Gingival Bleeding
The following case study focuses on a 26-year-old man who presents to the emergency room with a history of fatigue, fevers, and gingival bleeding for the past three days. Test your knowledge by reading the background information below and making the proper selection.
His physical exam reveals a young, pale skin man with notable ecchymosis and gingival bleeding, otherwise unremarkable. The patient’s white blood cell (WBC) count is 17.000/μl, hemoglobin is 9.4g/dl, and platelet count is 72,000/μl. The WBC differential notes 19 percent lymph, 15 percent monocytes, 6 percent eosinophils, and 60 percent others. The peripheral blood smear shows characteristic population with reddish-blue or dark-purplish cytoplasmic granules and creased, folded, or dumb-bell shaped nuclei. The patient is admitted for initiation of treatment. Subsequent FISH analysis documents a t(15;17) translocation.
What would be the optimal treatment plan for this patient?
Acute promyelocytic leukemia (APL) is one of the variants of acute myeloid leukemia (AML) and is biologically distinct from the other AML variants. The diagnosis of APL is suggested by the clinical features and the characteristic morphologic findings on the peripheral smear. The presentation with bleeding secondary to disseminated intravascular coagulation is unique to APL.
Almost all cases of APL are defined in molecular genetic terms by the presence of a reciprocal translocation between the long arms of chromosomes 15 and 17 (i.e., t[15;17][q22;q12]), with the creation of a fusion gene, PML/RAR-α.1,2 The chromosome breakpoint on chromosome 17 has been mapped to the site of the retinoic acid receptor-alpha (RARα) gene.3,4 Although it is unclear how this translocation results in leukemogenesis, there is evidence that PML/RARα impairs terminal differentiation and subsequent apoptosis of promyelocytes. The impaired interaction between the PML/RARα gene product and endogenous retinoids can be overcome by pharmacologic doses of retinoic acid, constituting the rationale for the use of this agent in the treatment of APL.
In a multivariate analysis of 217 patients with newly diagnosed APL treated in the Italian GIMEMA and the Spanish PETHEMA trials, adverse risk factors were a total WBC count >10,000/microL and a platelet count ≤40,000/microL.5 Using these two parameters, three prognostic categories could be distinguished, with the following estimated probabilities of three-year relapse-free survival (RFS):
Complete hematologic remissions induced by ATRA alone are rarely associated with complete molecular remissions and have had a median duration of only about 3.5 months.
Thus, remission induction therapy using a combination of ATRA plus cytotoxic chemotherapy appears necessary for long-term survival.
Results from a European randomized controlled study demonstrated the efficacy of ATRA in combination with chemotherapy for initial induction. This trial compared daunorubicin/cytarabine alone or in combination with ATRA.2 The study was stopped early when the first interim analysis showed that patients receiving ATRA had a significantly prolonged event-free survival at 12 months (79% vs. 50%) and a reduction in the relapse rate (19% vs. 40%).
The achievement of molecular remission rates of about 95 percent in patients receiving at least two further cycles of anthracycline-based chemotherapy after induction has led to adoption of this strategy as the standard for consolidation3and supports the clinical paradigm of achieving molecular remission as recommended by the International Working group.6
The role for cytarabine in the treatment of APL has been controversial. A recent randomized study of the European APL Group7 reported an increased risk of relapse when cytarabine was omitted from a schedule containing daunorubicin. A joint analysis of the PETHEMA group and European APL group8 noted a trend in favor of cytarabine for high-risk patients with a WBC higher than 10x109/L. In keeping with these results, the most recent Italian study suggests a benefit for cytarabine in combination with ATRA in patients with high-risk disease.9,10
Arsenic trioxide has differentiation, inductive, and apoptotic effects on APL cellsin vitro and has been shown to induce a high rate of complete remissions (CRs) in patients with recurrent APL. Arsenic trioxide degrades PML-RARα transcripts in the cell, but also acts through a PML-RARα independent cytotoxic mechanism.
Various smaller studies have reported on the use of arsenic trioxide in previously untreated patients. In one study, single-agent arsenic trioxide produced a high rate of CR and these remissions were shown to be durable in a significant number of patients.11 These results underscore the strong therapeutic effect of this drug.
A randomized North American Intergroup trial (CALGB 9710) investigated the safety and utility of adding two courses of arsenic trioxide (0.15 mg/kg per day for 5 days each week for 5 weeks) as a first consolidation treatment in 518 adults with newly diagnosed APL achieving CR or partial remission (PR) following a standard induction program. While the overall CR with 89 percent did not differ between the standard arm and the Arsenic arm, high-risk patients who received arsenic had improved DFS than those who did not receive arsenic.12 This study does not yet provide a definitive answer in regard to the place of arsenic trioxide in the current management of APL.
However, these recent studies investigating various risk-adapted treatment approaches in APL do suggest additional benefit for intensified consolidation with either arsenic or cytarabine for patients with high-risk features.
It is worth noting that, while a WBC>10.000 does define high risk for APL, the overall prognosis for these patients is still favorable compared to most otherAMLs.
The UK MRC investigated the role for allogeneic transplant in patients with high-risk features in APL in first CR in the pre-ATRA era and failed to show any benefit.13
Case study submitted by Tahamtan Ahmadi, MD, PhD, Hospital of University of Pennsylvania.
The following case study focuses on a 26-year-old man who presents to the emergency room with a history of fatigue, fevers, and gingival bleeding for the past three days. Test your knowledge by reading the background information below and making the proper selection.
His physical exam reveals a young, pale skin man with notable ecchymosis and gingival bleeding, otherwise unremarkable. The patient’s white blood cell (WBC) count is 17.000/μl, hemoglobin is 9.4g/dl, and platelet count is 72,000/μl. The WBC differential notes 19 percent lymph, 15 percent monocytes, 6 percent eosinophils, and 60 percent others. The peripheral blood smear shows characteristic population with reddish-blue or dark-purplish cytoplasmic granules and creased, folded, or dumb-bell shaped nuclei. The patient is admitted for initiation of treatment. Subsequent FISH analysis documents a t(15;17) translocation.
What would be the optimal treatment plan for this patient?
- This patient has a favorable prognostic chromosomal translocation and as such should receive standard "7+3" induction chemotherapy alone.
- This patient should receive ATRA (tretinoin) plus induction chemotherapy. Given his high-risk features as evidenced by the high WBC, an allogeneic transplant should be considered in first CR.
- The appropriate treatment for this patient includes ATRA plus induction chemotherapy and subsequent ATRA single-agent consolidation.
- This patient has high-risk features, and as such, will require additional consolidation therapy with either an arsenic trioxide or cytarabine-containing regimen.
- This patient has high-risk features, and as such, will require additional consolidation therapy with either an arsenic trioxide or cytarabine-containing regimen.
Acute promyelocytic leukemia (APL) is one of the variants of acute myeloid leukemia (AML) and is biologically distinct from the other AML variants. The diagnosis of APL is suggested by the clinical features and the characteristic morphologic findings on the peripheral smear. The presentation with bleeding secondary to disseminated intravascular coagulation is unique to APL.
Almost all cases of APL are defined in molecular genetic terms by the presence of a reciprocal translocation between the long arms of chromosomes 15 and 17 (i.e., t[15;17][q22;q12]), with the creation of a fusion gene, PML/RAR-α.1,2 The chromosome breakpoint on chromosome 17 has been mapped to the site of the retinoic acid receptor-alpha (RARα) gene.3,4 Although it is unclear how this translocation results in leukemogenesis, there is evidence that PML/RARα impairs terminal differentiation and subsequent apoptosis of promyelocytes. The impaired interaction between the PML/RARα gene product and endogenous retinoids can be overcome by pharmacologic doses of retinoic acid, constituting the rationale for the use of this agent in the treatment of APL.
In a multivariate analysis of 217 patients with newly diagnosed APL treated in the Italian GIMEMA and the Spanish PETHEMA trials, adverse risk factors were a total WBC count >10,000/microL and a platelet count ≤40,000/microL.5 Using these two parameters, three prognostic categories could be distinguished, with the following estimated probabilities of three-year relapse-free survival (RFS):
- Low risk — WBC ≤10,000 and platelets >40,000; RFS 98 percent
- Intermediate — WBC ≤10,000 and platelets ≤40,000; RFS 89 percent
- High risk — WBC >10,000; RFS 70 percent
Complete hematologic remissions induced by ATRA alone are rarely associated with complete molecular remissions and have had a median duration of only about 3.5 months.
Thus, remission induction therapy using a combination of ATRA plus cytotoxic chemotherapy appears necessary for long-term survival.
Results from a European randomized controlled study demonstrated the efficacy of ATRA in combination with chemotherapy for initial induction. This trial compared daunorubicin/cytarabine alone or in combination with ATRA.2 The study was stopped early when the first interim analysis showed that patients receiving ATRA had a significantly prolonged event-free survival at 12 months (79% vs. 50%) and a reduction in the relapse rate (19% vs. 40%).
The achievement of molecular remission rates of about 95 percent in patients receiving at least two further cycles of anthracycline-based chemotherapy after induction has led to adoption of this strategy as the standard for consolidation3and supports the clinical paradigm of achieving molecular remission as recommended by the International Working group.6
The role for cytarabine in the treatment of APL has been controversial. A recent randomized study of the European APL Group7 reported an increased risk of relapse when cytarabine was omitted from a schedule containing daunorubicin. A joint analysis of the PETHEMA group and European APL group8 noted a trend in favor of cytarabine for high-risk patients with a WBC higher than 10x109/L. In keeping with these results, the most recent Italian study suggests a benefit for cytarabine in combination with ATRA in patients with high-risk disease.9,10
Arsenic trioxide has differentiation, inductive, and apoptotic effects on APL cellsin vitro and has been shown to induce a high rate of complete remissions (CRs) in patients with recurrent APL. Arsenic trioxide degrades PML-RARα transcripts in the cell, but also acts through a PML-RARα independent cytotoxic mechanism.
Various smaller studies have reported on the use of arsenic trioxide in previously untreated patients. In one study, single-agent arsenic trioxide produced a high rate of CR and these remissions were shown to be durable in a significant number of patients.11 These results underscore the strong therapeutic effect of this drug.
A randomized North American Intergroup trial (CALGB 9710) investigated the safety and utility of adding two courses of arsenic trioxide (0.15 mg/kg per day for 5 days each week for 5 weeks) as a first consolidation treatment in 518 adults with newly diagnosed APL achieving CR or partial remission (PR) following a standard induction program. While the overall CR with 89 percent did not differ between the standard arm and the Arsenic arm, high-risk patients who received arsenic had improved DFS than those who did not receive arsenic.12 This study does not yet provide a definitive answer in regard to the place of arsenic trioxide in the current management of APL.
However, these recent studies investigating various risk-adapted treatment approaches in APL do suggest additional benefit for intensified consolidation with either arsenic or cytarabine for patients with high-risk features.
It is worth noting that, while a WBC>10.000 does define high risk for APL, the overall prognosis for these patients is still favorable compared to most otherAMLs.
The UK MRC investigated the role for allogeneic transplant in patients with high-risk features in APL in first CR in the pre-ATRA era and failed to show any benefit.13
Case study submitted by Tahamtan Ahmadi, MD, PhD, Hospital of University of Pennsylvania.
case study 2
I.Introduction
I personally selected this case of Acute Myelogenous Leukemia (AML) toenhance my knowledge concerning its clinical manifestations, possible causes,cure and prevention, among others. This knowledge will eventually become anindispensable tool that can be shared to others and will never go out of style. It isa privilege to embrace this challenge in the form of service to humanity and thefulfillment of our nursing profession. Our core competence is the bare essentialtowards its success.As a nursing profession, it is imperative to learn new techniques inmodern science in order to develop skills that would benefit the medical world.This learning potential must be relayed to posterity and develop new techniques,state -of –the- art technology that caters the modern man. In the final analysis, theachievement of one’s endeavor may usher us to find the light we are seeking for.First of all what is leukemia? Leukemia is a cancer of the blood, and ischaracterized by uncontrolled proliferation and accumulation of leukocytes (white blood cells). Most leukemic cells never mature into functioning leukocytes.Where in the body is deprived of vital components of its immune system. Also,the cells accumulate in the blood and in certain organs, forcing out healthy cellsand interfering with the function of that organ. There many different types of leukemia but the four most important forms are derived from only two types of cells, lymphocytes and myelocytes. Acute myelogenous leukemia is disorders .
for further reading , please refer to the link - http://www.scribd.com/doc/8659558/Case-Study-on-LEUKEMIA
case study 3
Patient A, a bright, energetic boy, 8 years of age, had shown less enthusiasm for his normal activities for a few days. He told his mother he felt tired and was sometimes nauseated, and his mother found that he had a low-grade fever (37.8 degrees Centigrade). Mrs. T, the patient's mother, took Patient A to his pediatrician, who noted no abnormalities on physical examination. He told Mrs. T that the patient probably had a virus. A week later, Patient A was still not feeling better, and Mrs. T took him to the pediatrician again. On physical examination, the pediatrician noted that the patient appeared pale and had slight lymphadenopathy. Suspecting infection, the pediatrician prescribed a 10-day course of an antibiotic. After completing the course of antibiotics, Patient A still did not feel better and continued to have a low-grade fever. At that time, the pediatrician noted ecchymoses of the skin and slight splenomegaly, findings that had not been previous evident. He ordered laboratory and imaging studies to rule out leukemia. The complete blood count demonstrated slight anemia and leukopenia; the chest x-ray was normal, and computerized tomography confirmed splenomegaly.
The signs and symptoms of pediatric leukemia are often insidious and persistent [28]. The most common symptom associated with ALL is a low-grade fever of unknown etiology [28]. Many symptoms related to leukemia are associated with other diseases and conditions, and care is needed in making a differential diagnosis. Reactive lymphadenopathy is common in children and adolescents, and clinicians should first rule out infectious or inflammatory conditions. Because of this, symptoms of ALL are present for an average of 4 to 6 weeks before the diagnosis is made [16,28]. Further evaluation for leukemia is warranted when fever persists for more than 2 weeks and when findings on physical examination include pallor, petechiae, ecchymoses of the skin or mucous membranes, or lymphadenopathy. Splenomegaly (or hepatomegaly) at the time of diagnosis of ALL is common [28]. Imaging studies should be carried out to determine the presence of leukemic involvement.
The pediatrician talked with Mr. and Mrs. T privately (without Patient A present) and carefully explained that their son may have leukemia and that he was referring Patient A to a pediatric cancer care center in a neighboring city. Patient A's parents were both devastated by the news. The pediatrician encouraged them to express their emotions and to ask questions. He patiently answered all questions, checking often to make sure they understood. He also reassured Mr. and Mrs. T that he would be available to talk with them or their son at any time. Mr. and Mrs. T told the pediatrician that they did not want Patient A to know about the diagnosis until it was confirmed. The pediatrician tried to persuade them to carefully consider this decision.
A cancer diagnosis is overwhelming for parents, and clinicians discussing the diagnosis should use clear language, encourage questions, check often for understanding, and offer reassurance and support. In addition, clinicians should elicit and validate parents' and patients' emotions [138]. The American Academy of Pediatrics recommends that clinicians refer children to pediatric cancer centers for diagnostic testing for leukemia (and lymphoma), where the availability of appropriate technology and subspecialists helps to ensure an accurate diagnosis [56]. Many parents wish to protect their child by withholding information about the diagnosis, but clinicians should encourage parents to share information with their child, as studies have shown that children often recognize the severity of their illness and wish to be included in discussions about diagnosis and treatment [145,146,147]. Open discussion can help a child feel less fear about the unknown and feel trust for their family and caregivers [145,147].
After much discussion, Mr. and Mrs. T decided not to tell Patient A the suspected diagnosis, but they did tell him he would need to see another physician and possibly have more tests. Patient A was concerned about the tests and wanted to know if they would be painful. The patient and his parents met with the pediatric oncologist, who performed a bone marrow aspiration, ensuring that Patient A was comfortable during the procedure. Examination of the bone marrow sample showed the presence of leukemic blast cells consistent with ALL. A lumbar puncture was performed, again ensuring that the patient was comfortable, and there was no evidence of leukemic involvement of the central nervous system. Cytogenetic examination of bone marrow cells demonstrated hyperploidy.
Pain interventions during diagnostic procedures are important, and the goal is to achieve unconsciousness, amnesia, and analgesia to ensure optimum comfort and cooperation [52]. Preventing pain during diagnostic procedures is also important to avoid a child's fear of future diagnostic testing and to avoid posttraumatic stress years later [53]. The sample obtained during bone marrow aspiration should be enough for both cytogenetic examination and immunophenotyping.
The pediatric oncologist met with Patient A and his parents to discuss the findings. Before the oncologist could discuss the diagnosis, Patient A's mother requested that the oncologist speak with only her and her husband before telling the patient. Both Mr. and Mrs. T seemed to be masking their emotions. The oncologist noted that Patient A should be included in the conversation, but Mr. and Mrs. T were adamant. Reluctantly, the oncologist discussed the diagnosis and prognostic factors with the parents only; he told them that the prognostic factors were favorable and noted that a clinical trial would be the best option. Mr. and Mrs. T began to express strong emotions, with Mrs. T crying and Mr. T becoming angry. They did not ask any questions, and Mr. T said he did not want his son to be a "guinea pig" in a clinical trial. The oncologist encouraged them to consider the decision carefully and to talk about the diagnosis with Patient A. When the oncologist suggested that Patient A be involved in the decision about participating in a clinical trial, both parents argued that he was too young to make such a decision. The oncologist provided Mr. and Mrs. T with educational resources and the names of some parents who had agreed to talk with parents of children with newly diagnosed leukemia. He also told them that a decision would need to be made quickly, as treatment should begin as soon as possible.
The emotional behavior of Mr. and Mrs. T indicates that they are having a difficult time dealing with their son's diagnosis. It is important for the clinician to be empathic and to encourage them to express their emotions. The clinician should also reiterate the importance of Patient A being involved with discussions about the diagnosis and treatment. Among the favorable prognostic factors are Patient A's age; age at the time of diagnosis is a strong prognostic factor, and disease-free survival is better for children 1 to 9 years of age than for other age groups [32,69]. In addition, hyperploidy is associated with a highly favorable prognosis [32,66]. These factors will allow treatment with a standard-risk protocol. Clinical trial participation should always be encouraged, as it provides the maximum opportunity for cure and long-term survival. The age threshold for a child participating in a discussion about a clinical trial has been debated, but most agree that individual decisions should be made on the basis of the child's level of maturity and physiologic and psychologic state [156,159]. The Children's Oncology Group recommends that the clinician and parents seek the child's perspective and that the clinician should encourage the parents and patient to make the decision jointly as a family [154]. During the clinical trial discussion, the clinician should discuss all facets of the clinical trial, emphasizing that a trial involves several possible treatment options, one of which is the treatment their child would receive outside of the clinical trial [162].Parents of children with cancer have suggested that providing educational resources and arranging for discussions with other parents are helpful for making decisions about a clinical trial [161].
Mr. and Mrs. T met with other parents and gained support for their emotional reactions. They also decided that Patient A should know about the diagnosis. He had many questions, and they arranged a meeting with the oncologist. The oncologist also discussed the possibility of a clinical trial, and Patient A said he wanted to participate; his parents supported his decision.
Patient A received induction therapy, CNS prophylaxis, consolidation therapy, and 3 years of maintenance therapy. Throughout his treatment, the patient received support from his extended family, friends, and classmates. He was tutored at home and managed to keep up with his school work. Four years after diagnosis, Patient A has no evidence of disease and he has returned to a "normal" life of school and activities. The pediatric oncologist documented the patient's complete diagnosis and a comprehensive account of treatment in a survivorship care plan, which he forwarded to the patient's pediatrician.
As Patient A continues routine health care, the survivorship care plan will provide the information his pediatrician and subsequent physicians need to understand his health risks according to his cancer type and its treatment [386,387]. His physicians should also consult the Children's Oncology Group's evidence-based guidelines for the long-term follow-up care of childhood cancer survivor to provide individualized follow-up care and screening [356,357]. Lastly, Patient A's physicians should use every healthcare visit as an opportunity to educate Patient A (and his parents) about his specific health risks and the importance of appropriate prevention measures, engaging in healthy lifestyle behaviors, and avoiding risky behaviors.
CASE STUDY 2
E is a Puerto Rican girl, 10 years of age, whose brother, Patient M, 5 years of age, is in the second year of his 3-year course of chemotherapy for ALL. Before Patient M was diagnosed with cancer, E enjoyed helping her mother with his care and teaching him how to count and to say the alphabet. E also enjoyed taking dance classes, and she and her classmates would visit each other's homes to practice. E's mother, Mrs. P, does not work outside the home and had been very involved in E's activities before the diagnosis. E's father, Mr. P, works full-time on the weekdays and paints houses on the weekends to ensure that the family can live in a nice neighborhood outside of the city. Several Puerto Rican families live in the neighborhood, and the P family enjoys close ties within this community. Both Mr. and Mrs. P speak Spanish as a first language and use English sparingly.
Because of the financial strain and the long drive to the hospital, the family moved into a 2-bedroom condominium closer to the hospital. E's family is the only Hispanic family in the complex, and E spends much time at home alone, as Mr. P continues to work two jobs and Mrs. P spends most of each day at the hospital. E's grades begin to drop, and she does not complete assignments or closely follow directions. E's teacher feels that she is disinterested in academics and her classmates. At home and at the hospital, E argues frequently with Mrs. P and cries often, saying that she wants to live with her friends in her former neighborhood because she feels "bored." In general, Mrs. P is embarrassed and frustrated by E's behavior. She often physically handles E following outbursts, resulting in E's crying and embarrassment. Conversely, Mrs. P is very kind to the staff and her son. If E is not present, Mrs. P does not exhibit signs of emotional distress.
E has lost many things that were important to her: dance lessons, familiar school, and friends, and her behavior and outbursts may be indicative of loneliness as well as jealously and resentment she feels against the time and attention Mrs. P provides Patient M. Cancer-free siblings are often reactive to the loss of day-to-day family routine, restrictions on their social activities, and inability to help their siblings with cancer. In addition, cancer-free siblings receive the least attention in the family, and their parents often overlook or underestimate their emotional and health-related responses [326]. E's feelings and behaviors increase the risk of unhealthy psychosocial adjustment and lower educational achievements.
Noting the emotional behaviors of E and her mother, Patient M's healthcare team seeks to provide psychosocial support for the family. A female member of the medical team who has been involved with Patient M's treatment and a professional interpreter arrange to talk with Mr. and Mrs. P and E independently so that they can share their concerns and express their emotions openly. The team member reassures the parents that E is expressing feelings and behaviors typical of cancer-free siblings. She acknowledges that the move has been difficult for the entire family, and points out that it is particularly so for E because of the social support she lost in addition to the time lost with her family. In the discussion with E, the team member acknowledges how difficult the adjustment is for E and emphasizes that her parents love her. E says that she misses being with her mother and brother and wishes she could be more involved. She also misses her father and wishes he could spend more time with the family. On the basis of the discussions with the family, the team member recommends several interventions, including a problem-solving skills training program for Mrs. P, family therapy, and a sibling program for E. The team member also encourages Mrs. P to involve E in Patient M's care and helps Mr. and Mrs. P seek additional practical resources to help them meet the challenges associated with Patient M's illness.
Family-centered care is essential in pediatric cancer, and the healthcare team must emphasize the importance of family cohesion and communication [334,35,336]. Helping Mr. and Mrs. P understand the reasons for E's behavior enhances the likelihood that they will agree to have her participate in a psychosocial intervention[339]. The use of a professional interpreter helps to make Mr. and Mrs. P more comfortable and provides for better comprehension [126]. The recommendation for a problem-solving program for Mrs. P is especially appropriate, as such training has been shown to have increased effectiveness for Spanish-speaking mothers[347]. Family therapy will help Mr. and Mrs. P and E communicate more openly with each other, and the therapeutic peer support group can help E with psychosocial adjustment.
Four months after the intervention, E says that she feels she has more of an active role in Patient M's treatment and that she is helping him with pain and emotional management. E is able to speak with her mother and father about problems at school and emotional aspects related to Patient M's cancer and the move. Mrs. P is noticeably affectionate with E. The family has received financial assistance with help from a cancer society, and Mr. P has negotiated with his employer to be off on every Friday and has quit his second job, allowing him to spend more time with his family. The family also makes arrangements to see friends in their former neighborhood occasionally. E is interacting with schoolmates again and is also performing better academically.
The signs and symptoms of pediatric leukemia are often insidious and persistent [28]. The most common symptom associated with ALL is a low-grade fever of unknown etiology [28]. Many symptoms related to leukemia are associated with other diseases and conditions, and care is needed in making a differential diagnosis. Reactive lymphadenopathy is common in children and adolescents, and clinicians should first rule out infectious or inflammatory conditions. Because of this, symptoms of ALL are present for an average of 4 to 6 weeks before the diagnosis is made [16,28]. Further evaluation for leukemia is warranted when fever persists for more than 2 weeks and when findings on physical examination include pallor, petechiae, ecchymoses of the skin or mucous membranes, or lymphadenopathy. Splenomegaly (or hepatomegaly) at the time of diagnosis of ALL is common [28]. Imaging studies should be carried out to determine the presence of leukemic involvement.
The pediatrician talked with Mr. and Mrs. T privately (without Patient A present) and carefully explained that their son may have leukemia and that he was referring Patient A to a pediatric cancer care center in a neighboring city. Patient A's parents were both devastated by the news. The pediatrician encouraged them to express their emotions and to ask questions. He patiently answered all questions, checking often to make sure they understood. He also reassured Mr. and Mrs. T that he would be available to talk with them or their son at any time. Mr. and Mrs. T told the pediatrician that they did not want Patient A to know about the diagnosis until it was confirmed. The pediatrician tried to persuade them to carefully consider this decision.
A cancer diagnosis is overwhelming for parents, and clinicians discussing the diagnosis should use clear language, encourage questions, check often for understanding, and offer reassurance and support. In addition, clinicians should elicit and validate parents' and patients' emotions [138]. The American Academy of Pediatrics recommends that clinicians refer children to pediatric cancer centers for diagnostic testing for leukemia (and lymphoma), where the availability of appropriate technology and subspecialists helps to ensure an accurate diagnosis [56]. Many parents wish to protect their child by withholding information about the diagnosis, but clinicians should encourage parents to share information with their child, as studies have shown that children often recognize the severity of their illness and wish to be included in discussions about diagnosis and treatment [145,146,147]. Open discussion can help a child feel less fear about the unknown and feel trust for their family and caregivers [145,147].
After much discussion, Mr. and Mrs. T decided not to tell Patient A the suspected diagnosis, but they did tell him he would need to see another physician and possibly have more tests. Patient A was concerned about the tests and wanted to know if they would be painful. The patient and his parents met with the pediatric oncologist, who performed a bone marrow aspiration, ensuring that Patient A was comfortable during the procedure. Examination of the bone marrow sample showed the presence of leukemic blast cells consistent with ALL. A lumbar puncture was performed, again ensuring that the patient was comfortable, and there was no evidence of leukemic involvement of the central nervous system. Cytogenetic examination of bone marrow cells demonstrated hyperploidy.
Pain interventions during diagnostic procedures are important, and the goal is to achieve unconsciousness, amnesia, and analgesia to ensure optimum comfort and cooperation [52]. Preventing pain during diagnostic procedures is also important to avoid a child's fear of future diagnostic testing and to avoid posttraumatic stress years later [53]. The sample obtained during bone marrow aspiration should be enough for both cytogenetic examination and immunophenotyping.
The pediatric oncologist met with Patient A and his parents to discuss the findings. Before the oncologist could discuss the diagnosis, Patient A's mother requested that the oncologist speak with only her and her husband before telling the patient. Both Mr. and Mrs. T seemed to be masking their emotions. The oncologist noted that Patient A should be included in the conversation, but Mr. and Mrs. T were adamant. Reluctantly, the oncologist discussed the diagnosis and prognostic factors with the parents only; he told them that the prognostic factors were favorable and noted that a clinical trial would be the best option. Mr. and Mrs. T began to express strong emotions, with Mrs. T crying and Mr. T becoming angry. They did not ask any questions, and Mr. T said he did not want his son to be a "guinea pig" in a clinical trial. The oncologist encouraged them to consider the decision carefully and to talk about the diagnosis with Patient A. When the oncologist suggested that Patient A be involved in the decision about participating in a clinical trial, both parents argued that he was too young to make such a decision. The oncologist provided Mr. and Mrs. T with educational resources and the names of some parents who had agreed to talk with parents of children with newly diagnosed leukemia. He also told them that a decision would need to be made quickly, as treatment should begin as soon as possible.
The emotional behavior of Mr. and Mrs. T indicates that they are having a difficult time dealing with their son's diagnosis. It is important for the clinician to be empathic and to encourage them to express their emotions. The clinician should also reiterate the importance of Patient A being involved with discussions about the diagnosis and treatment. Among the favorable prognostic factors are Patient A's age; age at the time of diagnosis is a strong prognostic factor, and disease-free survival is better for children 1 to 9 years of age than for other age groups [32,69]. In addition, hyperploidy is associated with a highly favorable prognosis [32,66]. These factors will allow treatment with a standard-risk protocol. Clinical trial participation should always be encouraged, as it provides the maximum opportunity for cure and long-term survival. The age threshold for a child participating in a discussion about a clinical trial has been debated, but most agree that individual decisions should be made on the basis of the child's level of maturity and physiologic and psychologic state [156,159]. The Children's Oncology Group recommends that the clinician and parents seek the child's perspective and that the clinician should encourage the parents and patient to make the decision jointly as a family [154]. During the clinical trial discussion, the clinician should discuss all facets of the clinical trial, emphasizing that a trial involves several possible treatment options, one of which is the treatment their child would receive outside of the clinical trial [162].Parents of children with cancer have suggested that providing educational resources and arranging for discussions with other parents are helpful for making decisions about a clinical trial [161].
Mr. and Mrs. T met with other parents and gained support for their emotional reactions. They also decided that Patient A should know about the diagnosis. He had many questions, and they arranged a meeting with the oncologist. The oncologist also discussed the possibility of a clinical trial, and Patient A said he wanted to participate; his parents supported his decision.
Patient A received induction therapy, CNS prophylaxis, consolidation therapy, and 3 years of maintenance therapy. Throughout his treatment, the patient received support from his extended family, friends, and classmates. He was tutored at home and managed to keep up with his school work. Four years after diagnosis, Patient A has no evidence of disease and he has returned to a "normal" life of school and activities. The pediatric oncologist documented the patient's complete diagnosis and a comprehensive account of treatment in a survivorship care plan, which he forwarded to the patient's pediatrician.
As Patient A continues routine health care, the survivorship care plan will provide the information his pediatrician and subsequent physicians need to understand his health risks according to his cancer type and its treatment [386,387]. His physicians should also consult the Children's Oncology Group's evidence-based guidelines for the long-term follow-up care of childhood cancer survivor to provide individualized follow-up care and screening [356,357]. Lastly, Patient A's physicians should use every healthcare visit as an opportunity to educate Patient A (and his parents) about his specific health risks and the importance of appropriate prevention measures, engaging in healthy lifestyle behaviors, and avoiding risky behaviors.
CASE STUDY 2
E is a Puerto Rican girl, 10 years of age, whose brother, Patient M, 5 years of age, is in the second year of his 3-year course of chemotherapy for ALL. Before Patient M was diagnosed with cancer, E enjoyed helping her mother with his care and teaching him how to count and to say the alphabet. E also enjoyed taking dance classes, and she and her classmates would visit each other's homes to practice. E's mother, Mrs. P, does not work outside the home and had been very involved in E's activities before the diagnosis. E's father, Mr. P, works full-time on the weekdays and paints houses on the weekends to ensure that the family can live in a nice neighborhood outside of the city. Several Puerto Rican families live in the neighborhood, and the P family enjoys close ties within this community. Both Mr. and Mrs. P speak Spanish as a first language and use English sparingly.
Because of the financial strain and the long drive to the hospital, the family moved into a 2-bedroom condominium closer to the hospital. E's family is the only Hispanic family in the complex, and E spends much time at home alone, as Mr. P continues to work two jobs and Mrs. P spends most of each day at the hospital. E's grades begin to drop, and she does not complete assignments or closely follow directions. E's teacher feels that she is disinterested in academics and her classmates. At home and at the hospital, E argues frequently with Mrs. P and cries often, saying that she wants to live with her friends in her former neighborhood because she feels "bored." In general, Mrs. P is embarrassed and frustrated by E's behavior. She often physically handles E following outbursts, resulting in E's crying and embarrassment. Conversely, Mrs. P is very kind to the staff and her son. If E is not present, Mrs. P does not exhibit signs of emotional distress.
E has lost many things that were important to her: dance lessons, familiar school, and friends, and her behavior and outbursts may be indicative of loneliness as well as jealously and resentment she feels against the time and attention Mrs. P provides Patient M. Cancer-free siblings are often reactive to the loss of day-to-day family routine, restrictions on their social activities, and inability to help their siblings with cancer. In addition, cancer-free siblings receive the least attention in the family, and their parents often overlook or underestimate their emotional and health-related responses [326]. E's feelings and behaviors increase the risk of unhealthy psychosocial adjustment and lower educational achievements.
Noting the emotional behaviors of E and her mother, Patient M's healthcare team seeks to provide psychosocial support for the family. A female member of the medical team who has been involved with Patient M's treatment and a professional interpreter arrange to talk with Mr. and Mrs. P and E independently so that they can share their concerns and express their emotions openly. The team member reassures the parents that E is expressing feelings and behaviors typical of cancer-free siblings. She acknowledges that the move has been difficult for the entire family, and points out that it is particularly so for E because of the social support she lost in addition to the time lost with her family. In the discussion with E, the team member acknowledges how difficult the adjustment is for E and emphasizes that her parents love her. E says that she misses being with her mother and brother and wishes she could be more involved. She also misses her father and wishes he could spend more time with the family. On the basis of the discussions with the family, the team member recommends several interventions, including a problem-solving skills training program for Mrs. P, family therapy, and a sibling program for E. The team member also encourages Mrs. P to involve E in Patient M's care and helps Mr. and Mrs. P seek additional practical resources to help them meet the challenges associated with Patient M's illness.
Family-centered care is essential in pediatric cancer, and the healthcare team must emphasize the importance of family cohesion and communication [334,35,336]. Helping Mr. and Mrs. P understand the reasons for E's behavior enhances the likelihood that they will agree to have her participate in a psychosocial intervention[339]. The use of a professional interpreter helps to make Mr. and Mrs. P more comfortable and provides for better comprehension [126]. The recommendation for a problem-solving program for Mrs. P is especially appropriate, as such training has been shown to have increased effectiveness for Spanish-speaking mothers[347]. Family therapy will help Mr. and Mrs. P and E communicate more openly with each other, and the therapeutic peer support group can help E with psychosocial adjustment.
Four months after the intervention, E says that she feels she has more of an active role in Patient M's treatment and that she is helping him with pain and emotional management. E is able to speak with her mother and father about problems at school and emotional aspects related to Patient M's cancer and the move. Mrs. P is noticeably affectionate with E. The family has received financial assistance with help from a cancer society, and Mr. P has negotiated with his employer to be off on every Friday and has quit his second job, allowing him to spend more time with his family. The family also makes arrangements to see friends in their former neighborhood occasionally. E is interacting with schoolmates again and is also performing better academically.