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Acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL), also known as acute lymphocytic leukemia, is a cancer of the white blood cells, characterised by the overproduction and continuous multiplication of malignant and immature white blood cells (referred to as lymphoblasts) in the bone marrow. It is a hematological malignancy. It is fatal if left untreated as ALL spreads into the bloodstream and other vital organs quickly (hence "acute"). It mainly affects young children and adults over 50. more...

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Initial symptoms of ALL are quite aspecific, but worsen to the point that medical help is sought:

  • Generalised weakness and fatigue
  • Anemia
  • Frequent or unexplained fever and infections
  • Weight loss and/or loss of appetite
  • Excessive bruising or bleeding from wounds, nosebleeds, petechiae (red pinpoints on the skin)
  • Bone pain, joint pains (caused by the spread of "blast" cells to the surface of the bone or into the joint from the marrow cavity)
  • Breathlessness
  • Enlarged lymph nodes, liver and/or spleen

The signs and symptoms of ALL result from the lack of normal and healthy blood cells because they are crowded out by malignant and immature white blood cells. Therefore, people with ALL experience symptoms from their red blood cells, white blood cells, and platelets not functioning properly. Laboratory tests which might show abnormalities include blood counts, renal functions, electrolytes and liver enzymes.


Diagnosing leukemia usually begins with a medical history and physical examination. If there is a suspicion of leukemia, the patient will then proceed to undergo a number of tests to establish the presence of leukemia and its type. Patients with this constellation of symptoms will generally have had blood tests, such as a full blood count.

These tests may include complete blood count (blasts on the blood film generally lead to the suspicion of ALL being raised). Nevertheless, 10% have a normal blood film, and clinical suspicion alone may be the only reason to perform a bone marrow biopsy, which is the next step in the diagnostic process.

Bone marrow is examined for blasts, cell counts and other signs of disease. Pathological examination, cytogenetics (e.g. presence of the Philadelphia chromosome) and immunophenotyping establish whether the "blast" cells began from the B lymphocytes or T lymphocytes.

If ALL has been established as a diagnosis, a lumbar puncture is generally required to determine whether the malignant cells have invaded the central nervous system (CNS).

Lab tests (mentioned above) and clinical information will also determined if any other medical imaging (such as ultrasound or CT scanning) may be required to find invasion of other organs such as the lungs or liver.


The etiology of ALL remains uncertain although some doctors believe that ALL develops from a combination of genetic and environmental factors. However, there is no definite way of determining the cause of leukemia.

Scientific research has shown that all malignancies are due to subtle or less subtle changes in DNA that lead to unimpaired cell division and breakdown of inhibitory processes. In leukemias, including ALL, chromosomal translocations occur regularly. It is thought that most translocations occur before birth during fetal development. These translocations may trigger oncogenes to "turn on", causing unregulated mitosis where cells divide too quickly and abnormally, resulting in leukemia. There is little indication that propensity for ALL is passed on from parents to children.


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Relationships Between Specific Measures of Body Function, Activity, and Participation in Children with Acute Lymphoblastic Leukemia
From Rehabilitation Oncology, 1/1/04 by Marchese, Victoria G


Because of the increasing survival rates for children with acute lymphoblastic leukemia (ALL) and the extensive side effects of the treatments, it is important to examine the relationships between specific measures of body function, activity, and participation to assist in developing appropriate physical therapy intervention programs. The study population comprised 29 children (age, 4 to 17 years) with ALL from The Children's Hospital of Philadelphia. For use as indicators of body function, hemoglobin, ankle dorsiflexion active range of motion, and ankle dorsiflexion and knee extension strength were measured with blood levels, goniometry, and hand-held dynamometry, respectively. Activity was measured through the Timed Up and Down Stairs and 9-Minute Run-Walk tests. Participation was indicated by a health-related quality of life measure, the PedsQL. Our findings identified relationships between specific measures of body function, activity, and participation. We therefore recommend that therapists provide interventions with equal emphasis on all 3 components to offer a comprehensive program.


Children with acute lymphoblastic leukemia (ALL) are at risk for developing short- and long-term impairments in body function, activity limitations, and participation restrictions. Some of these include decreased hemoglobin levels,1 osteonecrosis,2,3 ankle dorsiflexion active and passive range of motion,4,5 strength,5-7 gross and fine motor performance,8-10 fitness,11-13 and attendance in school.14

Physical therapists strive toward providing children with interventions that produce meaningful functional outcomes and ultimately maximizes the children's ability to participate in school, play, and the activities of daily living.15 To provide a comprehensive physical therapy intervention program, therapists may need to address body function, activity, and participation for children with ALL to promote health and prevent secondary complications. Identifying any relationships between these 3 components will assist therapists in determining intervention programs that may emphasize specific components to achieve maximal outcomes.

A previous study of children with ALL (age, 4 to 15 years) who were in the delayed intensification phase of chemotherapy identified a strong correlation (r = -0.79, p

We used the International Classification of Functioning, Disability, and Health (ICIDH-2),18 a health classification system, as the framework for the present study. The ICIDH-2 classifies functioning at the levels of body/part (body function), whole person (activity), and whole person in social context (participation) and proposes that the complex relationship between these three components affects health conditions.

The aim of the present study was to assess the relationships between specific measures of body function (hemoglobin levels, ankle dorsiflexion active range of motion [AROM], ankle dorsiflexion and knee extension strength), activity (assessed using the Timed Up and Down Stairs [TUDS] and 9-Minute Run-Walk tools), and participation (as reported through the PedsQL measure) in children with ALL and to quantify the variance in participation explained by body function and activity. An understanding of the relationship between body function, activity, and participation will provide some evidence for therapists in their decision-making process when selecting a framework for intervention programs for children with ALL. Our hypothesis was that there is a relationship among measures of body function, activity, and participation in children with ALL. Further, we hypothesized there would be little relationship (r = 0.00 to 0.25) between an isolated body function measure (eg, hemoglobin, ankle dorsiflexion active range of motion, ankle dorsiflexion, and knee extension strength) and a multidimensional measure of participation (PedsQL) and a moderate relationship (r = 0.50 to 0.75) between activity measures that encompass whole body function (eg, TUDS, 9-Minute Run-Walk) and participation (PedsQL).



The study population comprised 29 children (male, 20; female, 9) with ALL who were 4 to 17 years of age (mean, 8.3, SD = 2.9). All the children were receiving maintenance chemotherapy and were 8 to 32 months from diagnosis. The children were treated according to risk-stratified Children's Cancer Group (CCG) protocols at The Children's Hospital of Philadelphia (CHOP). The exclusion criteria for the study included previous history of cancer, history of a neurologic disorder prior to the diagnosis of ALL, diagnosis of a developmental or genetic disorder, and currently receiving physical therapy services. Physician approval, consent from the parent, and assent from the child prior to his or her participation in the study were obtained. The study was approved by the Institutional Review Boards of The Children's Hospital of Philadelphia and MCP Hahnemann University. The children in this study were participants in a larger study that examined the effects of physical therapy intervention in children with ALL receiving chemotherapy.5

Measurement Tools

Hand-held dynamometry (Nicholas Hand-Held Dynamometer, Lafayette Instruments, Lafayette, IN) was used to measure knee extension strength and ankle dorsiflexion strength.19 Ankle dorsiflexion active range of motion was measured with a goniometer.20 The Timed Up and Down Stairs measure was used to represent functional mobility. The TUDS test requires the children to ascend and descend 12 stairs as fast as possible.21,22 The 9-Minute Run-Walk test was used to measure maximal functional capacity and endurance of the cardiorespiratory system.23 Children are instructed to run as far as possible in 9 minutes; they are allowed to walk, but the objective is to cover as much distance as possible during the 9 minutes.21

The PedsQL (Pediatric Quality of Life Inventory 4.0 and Cancer Module 3.0) measure was used to assess health-related quality of life. This tool incorporates a general core and disease/symptom-specific modular approach for pediatric chronic health conditions.24,25 There are separate versions for 4 age groups: toddler (2 to 4 years of age), young child (5 to 7 years), child (8 to 12 years), and adolescent (13 to 18 years). The PedsQL allows for parent and child proxy. There are 4 separate questionnaires that may be completed: the child general PedsQL, parent general PedsQL, child cancer PedsQL, and parent cancer PedsQL. Children younger than 5 years do not fill out the forms because of the difficulty they may have with reading and understanding the questions.24 The PedsQL generic core form consists of the following scales: physical functioning, emotional functioning, social functioning, and school functioning. The disease/symptom-specific module addresses (1) pain and hurt, (2) nausea, (3) procedural anxiety, (4) treatment anxiety, (5) worry, (6) cognitive problems, (7) perceived physical appearance, and (8) communication skills.

Testing Procedures

Two experienced physical therapists performed all the testing. For 27 of the children, testing was done at either CHOP or a satellite clinic; the remaining 2 children were seen in the home. Approximately 1 hour was required to perform all testing procedures. When measuring knee extension strength, each child was positioned in prone with the knee flexed to 90° and the thigh stabilized. Ankle dorsiflexion strength was measured with the child long-sitting with the knee extended and the ankle in neutral (90°). The child's weight, measured on a standard scale, was obtained from the medical record and had been taken within 2 weeks of the testing session. Weight was used to normalize the dynamometer strength measures. Ankle dorsiflexion AROM was measured with each child sitting with the knee flexed to 90° and the foot in neutral alignment.20

The time needed for each child to ascend and descend 12 stairs was measured using a stopwatch. The use of a railing was permitted. In addition, each child was asked to run or walk as far as possible for 9 minutes; the distance was measured to the nearest foot with a wheeled counter once the test was completed. The 9-Minute Run-Walk was performed indoors for children tested at CHOP or satellite clinics; the children tested at home performed the test outdoors.

Children and parents completed the PedsQL measure (general and cancer-specific) at the end of the testing session. The primary investigator obtained the children's hemoglobin levels from the medical record. These blood levels were obtained within 2 weeks of the physical therapy testing session. Hemoglobin measures were examined to observe changes in physiologic stability.

Data Analysis

Pearson product-moment correlation coefficients were used to examine the relationships between hemoglobin level, ankle dorsiflexion AROM, ankle dorsiflexion and knee extension strength, TUDS, 9-Minute Run-Walk, and parent and child PedsQL. Data were analyzed on 29 subjects for all correlations except those involving the PedsQL, for which there were data from 28 subjects; one child lived in a group home where a parent was not available. In addition, only 28 children completed the child general and cancer-specific PedsQL because 1 child was only 4 years of age, and patient proxy is not available for children younger than 5 years.

Stepwise estimation regression analyses were performed to examine the variance in participation explained by body function and activities. The independent variables entered into the regression analyses were body function (hemoglobin level, dorsiflexion active range of motion, and ankle dorsiflexion and knee extension strength) and activity (TUDS, 9-Minute Run-Walk). The dependent variables were the parent general, parent cancer, child general, and child cancer PedsQL scores. A regression analysis was performed for each dependent variable.


Relationships Between Body Function and Activity Measures

The correlation results are presented in Table 1. Ankle dorsiflexion strength scores were correlated with TUDS (r = 0.41) and 9-Minute Run-Walk (r = 0.42). All other body function and activity variables were not significantly correlated.

Variance in Participation Explained by Body Function and Activity

Table 2 depicts the correlations between body function, activity, and participation measures. TUDS was the only variable that correlated with the parent general PedsQL (Table 2). Children with more efficient TUDS scores had less frequency of problems as reported by parents on the general PedsQL measure. Ankle dorsiflexion strength and knee extension strength were the only variables that correlated with the child cancer PedsQL (Table 2). Children with greater strength had more frequency of problems reported on the child cancer PedsQL measure. For the parent general PedsQL, only TUDS was accepted into the regression equation. Eighteen percent of the variance accounted for in the parent general PedsQL was explained by the TUDS. For the child cancer PedsQL, only ankle dorsiflexion strength was accepted into the regression equation. Twenty-two percent of the variance accounted for in the child cancer PedsQL was explained by ankle dorsiflexion strength. None of the independent variables were entered into the regression equation for parent cancer and child general PedsQL measures.


The data failed to support our hypothesis that there would be a moderate relationship (r = 0.50 to 0.75) between specific measures of activity and participation. However, there was a fair correlation between TUDS and parent general PedsQL scores (r = 0.42), but the activity variables and the parent cancer PedsQL were not related. The general PedsQL has a physical functioning scale that the cancer PedsQL lacks. The physical functioning scale included questions such as, "In the past month, how much of a problem have you had with walking more than 1 block? Participating in sports activities? Doing chores? Having hurts or aches? Having a low energy level?" Parents perceived a lower frequency of problems regarding the general PedsQL items when their children performed the TUDS relatively faster. This finding may reflect a parent's perception that ascending and descending stairs is a task that relates to their children's participation in their daily routines.

Our hypothesis of a moderate relationship between activity measures (TUDS and 9-Minute Run-Walk) and participation measures (PedsQL) was not accepted for the child general PedsQL or the child cancer PedsQL. Further the TUDS and 9-Minute Run-Walk scores did not explain the variance in the children's PedsQL. This finding is not consistent with the relationship identified between the TUDS and the parent general PedsQL, in light of the fact that the child general PedsQL also contains a physical functioning scale.

Body function measures (hemoglobin level, ankle dorsiflexion active range of motion, and ankle dorsiflexion and knee extension strength) did not explain any of the variance in the PedsQL as identified through the parents general and cancer PedsQL and the children's general PedsQL. However, relationships were identified between child cancer PedsQL and ankle dorsiflexion strength (r = 0.47) and between this measure and knee extension strength (r = 0.45).

Because the two strength measures were related (r = 0.61), only the ankle dorsiflexion strength measure was entered into the regression equation because it had the higher correlation coefficient. Children with higher ankle dorsiflexion strength perceived an increased frequency of problems, according to the responses to the questions on the cancer PedsQL. This result may reflect the situation that the children with greater strength were possibly those who participated in organized sports and were more physically active. Therefore these children may have been more aware of their participation limitations than were other children, who were not involved in such activities.

Why there was a relationship between the strength measures and the child cancer PedsQL but not with the child general PedsQL is unclear. The child general PedsQL had the items pertaining to physical function and the child cancer PedsQL addressed questions on pain, anxiety, cognitive problems, perceived physical appearance, and communication. A possible consideration was as children become older strength increases, and older children may perceive greater problems with physical appearance and communication. However, post-hoc analysis identified that age did not significantly correlate with the child cancer PedsQL.

Even though 18% (parent general PedsQL) and 22% (child cancer PedsQL) of the variance accounted for was explained by the TUDS and ankle dorsiflexion strength, respectively, other variables may have influenced these relationships. The child's environment may need to be considered because if there are no stairs in a child's home or school, stair climbing may not be perceived to impact the child's health-related quality of life. Personal factors such as a family's cultural beliefs may influence how children and parents perceive the importance of the tested variables in relation to health-related quality of life. In addition, because of the small correlation coefficients it is difficult to know whether the TUDS and ankle dorsiflexion strength can explain a parent's perception of their child's health-related quality of life or the child's perception of their own health-related quality of life, especially because the findings were not consistent across parent and child or general and cancer PedsQL measures.

The constructs and measurement tools in this study need to be considered when interpreting the results. The body function components measured were very specific (eg, range of motion of a single joint, strength measures for two muscle groups). Although these measures were chosen based on knowledge that children with ALL may have impairments of these body functions, these measures do not represent all possible body function impairments. In addition, although the activity components measured require multiple body functions, including active range of motion, strength, and endurance, they were still very specific to the tasks of ascending and descending stairs (TUDS) and walking and running (9-Minute Run-Walk). Other tasks that may be important to children but perhaps not well addressed by the measures used are riding a bike, swimming, dancing, and karate. Further, the tool we used to measure health-related quality of life was an aggregate measure. The total parent and child general PedsQL scores included items pertaining to physical, emotional, social, and school functioning; and the parent and child cancer total PedsQL scores included items referring to pain, nausea, anxiety, cognitive problems, perceived physical appearance, and communication. The positive aspect of the PedsQL was the broad scope of the measure-a multidimensional approach to participation. However this may have influenced analyses in our study because the numbers of questions pertaining to physical performance and participation in daily routines were limited.

Children and parents did not perceive having problems with the items measured by the PedsQL. Therefore the measurement tool may not have been sensitive enough for our patient population to identify a decrease in health-related quality of life even when the children had identified body function impairments and activity limitations. The PedsQL measured the frequency children and parent's perceived having problems with the items but did not identify difficulties or concerns with quality of how the children performed activities. A recommended alternative to the PedsQL is to use goal attainment scaling to generate individualized outcomes for participation.26

The children in our study were physically active: 82% of the children participated in gym class. The children reported playing soccer, riding horses, swimming, hiking, riding bikes, playing basketball, and dancing. The children's body function impairments and activity limitations may be too subtle to affect health-related quality of life. We recommend investigation of the relationships among measures of body function, activity, and participation when children are in the early phases of chemotherapy.

Our findings also need to be interpreted based on the limitations of the small sample size, sample population, and location of the testing sessions. The peak incidence rate of ALL occurs in children 2 to 5 years of age whereas the youngest child in our study population was 4 years old. Our present results cannot be generalized to younger children with ALL. Although the testing location was not consistent for all children in the study, efforts were made to ensure a safe and optimal environment.


Our present study identified significant relationships between ankle dorsiflexion strength and TUDS score, ankle dorsiflexion strength and 9-minute Run-Walk score, ankle dorsiflexion strength and child cancer PedsQL responses, knee extension strength and child cancer PedsQL responses, and TUDS score and parent general PedsQL responses. Because we examined relationships between specific measures only and until further research expands upon our findings, we recommend that therapists provide interventions with equal emphasis on all 3 components to offer a comprehensive program. Additional studies need to be performed to determine whether relationships between body function, activity, and participation arise when testing occurs earlier in the children's chemotherapy treatment and to explore outcomes when other joint range of motion, strength measures, functional tests, and individualized measures for participation are performed.


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Victoria G. Marchese, PT, PhD1

Lisa A. Chiarello, PT, PhD, PCS2

1 Rehabilitation Services, St. Jude Children's Research Hospital, Department of Physical Therapy, The Children's Hospital of Philadelphia, Programs in Rehabilitation Sciences, Drexel University

2 Programs in Rehabilitation Sciences, Drexel University

Copyright Rehabilitation in Oncology 2004
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