Hematologic malignancies refer to cancers of the blood, bone marrow and lymph nodes. The bone marrow transplant (often referred to as hematopoietic stem cell transplant) is a treatment often used to treat hematologic malignancies. Uncommonly, some solid tumors are also treated with bone marrow transplants. It consists of an infusion of bone marrow stem cells to replace cancerous cells.
These cancers develop in blood, bone marrow, and lymph nodes. Chromosomal translocations often are the root cause of the cancers. Hematologic cancers include leukemia, pre-leukemic conditions (e.g., myelodysplastic syndrome and aplastic anemia), lymphoma, multiple myeloma, and other associated diseases such as Waldenstrom macrogloblinemia and amyloidosis.
Epidemiology including risk factors and primary prevention
Hematologic malignancies account for 9.6% of the approximately 1,450,000 new cancer cases. New lymphoma cases outnumber leukemia cases.
Inappropriate replication of cancerous cells leads to increased viscosity of the blood, increased susceptibility to infections, and cytopenias of other cells lines.
Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)
Patients may experience a number of symptoms including fatigue, infections, weight loss, swollen lymph nodes, and bleeding. The initial symptoms often require a work-up including blood work that eventually leads to the diagnosis. Abnormalities in cell blood counts are common and can affect white blood cells, red blood cells, and platelet levels.
Patients are initially treated with three stages of chemotherapy. The first is induction chemotherapy which aims to acutely decrease abnormally high blood counts. The second, or consolidation phase, refers to chemotherapy used to achieve remission of the hematologic cancer. The maintenance phase is chemotherapy given after remission to keep the cancer from returning.
Many patients will be offered hematopoietic stem cell transplants (SCT). Donors for the stem cells can be autologous (from the patient) or allogeneic (from someone else). Allogeneic stem cells can be from a matched unrelated donor or a matched related donor (usually a sibling). Stem cells can be harvested peripherally or from umbilical cords.
Specific secondary or associated conditions and complications
Patients can present with a number of symptoms that should be addressed by physiatry.
- Chemotherapy Induced Peripheral Neuropathy (CIPN) is associated with the use of chemotherapy agents. Platinum (e.g., cisplatin), taxol (e.g., pacilitaxel) agents, vincristine, and bortezomib in particular are associated with CIPN. The CIPN can result in pain, weakness, and numbness, all of which can affect function. Patients with a preexisting neuropathy may be more at risk for developing symptoms.
- Steroid Myopathy is commonly associated with prolonged use of steroids. Steroids are often used in SCT patients to prevent or limit graft versus host disease (GVHD) and are often part of chemotherapy protocols. Patients present with predominantly Type IIB muscle fiber atrophy and proximal greater than distal weakness. This results in difficulty with sit-to-stand transfers and ascending/descending stairs.
- Deconditioning/Asthenia is due to the inflammatory and hormonal effects of the cancer and its treatment, medical complications, prolonged immobility, and inadequate nutrition. Fatigue is commonly associated with this. 1,2,3,4 Gastrointestinal and oral mucosal GVHD may further reduce oral intake and exacerbate malnutrition.
- Cognitive dysfunction can be the result of a number of causes, including a condition called “chemo-brain”, or due to the presence of CNS lesions or leptomeningeal disease. Other causes include cerebrovascular accidents, both hemorrhagic from thrombocytopenia and ischemic from hypercoagulability.5
- Graft Versus Host Disease (GVHD) is a common occurrence after a hematopoietic stem cell transplant. Symptoms vary on the site of the GVHD. Gastrointestinal GVHD can cause significant abdominal pain, nausea, diarrhea and weakness. Skin and fascia are the most common sites for GVHD and can result in skin lesions and skin contractures. Although not well studied, positioning,range of motion exercises and splinting may be of some utility.
- Edema. Patients can suffer from edema due to malnutrition/hypoproteinemia, venous thrombosis and lymphedema. This can have both pain and functional implications. The use of lymphedema wrapping techniques (whether or not the etiology is truly lymphatic dysfunction) may be of benefit. Intravenous infusion of albumin and diuretics are also used. Monitoring of cardiac and renal status is recommended.6
- Avascular necrosis – typically affects major joints including the femoral heads, knees, and shoulders. Chronic use of steroids, older age, female sex, diabetes, tobacco use, lupus, renal transplant, sickle cell anemia, alcoholism and hematologic malignancy are risk factors.7 A history of radiation treatment, use of anti-estrogen medications and certain cytotoxic chemotherapies have also been implicated.8
- Osteoporosis – patients are at increased risk of osteoporosis due to hormonal and inflammatory changes. Up to 50% of post-SCT patients have osteoporosis.9
A number of issues need to be taken into account when treating this patient population:
- Leukopenia and neutropenia can be of concern. Patients may be at high risk for infection and could benefit from reverse isolation and refraining from group therapy sessions.
- Anemia and thrombocytopenia can affect energy levels and ability to participate in therapy. Falls in these patients can be particularly severe due to their bleeding risk.
2. ESSENTIALS OF ASSESSMENT
History should include prior and ongoing cancer treatments, symptoms, complications, and specific impairments. A thorough symptom assessment, including fatigue, pain, and cachexia should be performed. Medications should be reviewed for chemotherapy agents, steroids, or antimicrobial agents.
Physical examination should include evaluating the lungs, mouth, and skin for signs of infection. Pneumonia, oral candidiasis, and herpes oral lesions are commonly found due to their immunosuppression. A detailed neurologic examination should include evaluation of strength, sensation (including proprioception) and cognition.
A musculoskeletal examination may reveal abnormalities that are common in these patients. Muscle atrophy and edema are common. Range of motion should be evaluated in patients with dermatologic GVHD.
An evaluation of transfers, stairs, gait, and endurance are needed.
Laboratory studies should include frequent cell blood counts in patients with pancytopenia. Nutrition and fatigue laboratory studies may be useful, including prealbumin, C-reactive protein, and albumin. A fatigue panel may be useful, consisting of a comprehensive metabolic panel, complete blood count (CBC), vitamin D test, iron test, urinalysis (UA) test, thyroid panel, and hormones, including testosterone (in males). In leukemia patients, a peripheral blast percentage may indicate disease status.
Imaging studies may be helpful in detection of infections especially in immunocompromised patients. Central nervous system imaging is indicated in patients suffering from new neurologic symptoms to rule our metastasis. Patients may be at increased risk of fracture and avascular necrosis due to chronic steroid use. X-rays may be needed in patients with new pain.
Supplemental assessment tools
Clinician assessment tools include the 6-minute walk, FIM score, timed get up and go, Karnofsky score and ECOG score. Patient reported assessment tools include PROMIS and Edmonton Symptom and Assessment Scale.
Early predictions of outcomes
For inpatient rehabilitation, the Return to Primary Bone Marrow Transplant index and the Return to Primary Leukemia Index may be useful in predicting which patients are likely to suffer from medical complications while on inpatient rehabilitation. 10,11 These indices are unvalidated.
Functional assessments should take into account the patient’s home setting. Stairs can be particular difficult for patients with steroid myopathy, and their medical outpatient follow-up appointments can also make for long exhausting days. Patients may require daily blood checks and daily transfusions which can take hours.
Social role and social support system
An evaluation of the social support network should take into account transportation, monetary resources, and available family members. Stem cell transplant patients often must stay close to the hospital with a family member for several months post-transplant.
Physiatrists may provide a great deal of hope to cancer patients, even those with a limited prognosis. Rehabilitation is a phase of treatment where patients can recognize demonstrable gains despite difficult circumstances. Providing realistic support and encouragement can assist patients in persevering through their therapies.
3. REHABILITATION MANAGEMENT AND TREATMENTS
Available or current treatment guidelines
No specific rehabilitation treatment guidelines exist at this time.
At different disease stages
Dietz divided cancer rehabilitation into four stages.12
The first is the preventive stage. Similar approaches have been coined ”buffering” or “prehabilitation.” This stage of cancer rehabilitation occurs before the onset of major treatment. In the case of hematologic patients, rehabilitation before chemotherapy or a stem cell transplant would be an example.
The second type/stage of cancer rehabilitation is supportive rehabilitation. This occurs during cancer treatment. Cancer rehabilitation for long-term cancer survivors would be of this nature.
The third type stage of cancer rehabilitation is restorative. This occurs after a recent cancer treatment to restore function. Most rehabilitation in an inpatient setting is of this category.
The fourth type is palliative. This is done near the end of life. An example would be preparing a patient for discharge home after no further cancer treatment is available. Rehabilitation goals are typically more modest, and given the reduced life expectancy, emphasis is on returning the patient home as soon as possible.
Coordination of care
Coordinating care with the patient’s oncologist and other physicians is necessary during cancer treatment. Patients often have specific chemotherapy regimens and specific treatment protocols that need to be adhered to. Care of the pancytopenia and other medical complications such as infections need to be addressed.
The cancer adaptation team (CAT), which consists of a team of therapists, physiatrist, and nurse, is a model of care useful for rehabilitating patients while on the primary acute care team service. The model published by the Mayo clinic in the 1990s allows intense rehabilitation while the patient receives ongoing cancer treatment.13
Survivorship care is an area of intense growth for cancer rehabilitation.14 Coordinating care with other specialties to address the symptoms and comorbidities of these patients is important.
Patient & family education
Patients and families should be educated about their cancer and its potential effects on energy, endurance, strength, and bleeding, among others. Precautions should be taken with respect to anemia, thrombocytopenia, neutropenia, and hypovolemia.
A number of measuring instruments can be utilized. For patients who acutely have suffered a significant functional decline, measurements such as the FIM, 6-minute walk, ECOG, and Karnofsky can be used.
Higher level cancer survivors may be more accurately described using measurement scores such as the PROMIS and FACT.
Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills
Cancer rehabilitation, in addition to quality of life, may also have an impact on medical outcomes. For example, cancer treatment is often not offered to patients who are severely debilitated.
4. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE
5. GAPS IN THE EVIDENCE-BASED KNOWLEDGE
Gaps in the evidence-based knowledge
Current research suggests many symptoms that cancer patients suffer from are related to pro-inflammatory cytokines due to cancer and its treatment. Research also suggests that exercise and activity can reduce these symptoms in cancer patients. There is also research in the non-cancer realm that exercise/activity can induce an anti-inflammatory effect which can improve similar symptoms in non-cancer patients. There is no published research on the effects of exercise programs on inflammatory cytokines in the cancer population. It is postulated that the improvement in cancer symptoms from exercise is due to an anti-inflammatory mechanism.
- Dimeo FC. Effects of exercise on cancer-related fatigue. Cancer. 2001;92(6 Suppl): 1689-1693.
- Persoon S, Kersten MJ, van der Weiden K, et al. Effects of exercise in patients treated with stem cell transplantation for a hematologic malignancy: A systematic review and meta-analysis. Cancer Treat Rev. Cancer Treat Rev. 2013 Oct;39(6):682-90.
- Siefert ML (2010) Fatigue, pain, and functional status during outpatient chemotherapy. Oncol Nurs Forum. 2010;37(2):E114-E123.
- Bertheussen GF, Kaasa S, Hokstad A, et al. Feasibility and changes in symptoms and functioning following inpatient cancer rehabilitation. Acta Oncol. 2012 Nov;51(8):1070-80.
- Moleski M. Neuropsychological, neuroanatomical, and neurophysiological consequences of CNS chemotherapy for acute lymphoblastic leukemia. Arch Clin Neuropsychol. 2000;15(7):606-630.
- Kerchner K, Fleischer A, Yosipovitch G. Lower extremity lymphedema update: pathophysiology, diagnosis, and treatment guidelines. J Am Acad Dermatol. 2008 Aug;59(2):324-31.
- Seamon J, Keller T, Saleh J, Cui Q. The pathogenesis of nontraumatic osteonecrosis. Arthritis. 2012;2012:601763.
- Shim K, MacKenzie MJ, Winquist E.Chemotherapy-associated osteonecrosis in cancer patients with solid tumours: a systematic review. Drug Saf. 2008;31(5):359-71.
- McClune BL, Polgreen LE, Burmeister LA, Blaes AH, Mulrooney DA, Burns LJ, Majhail NS. Screening, prevention and management of osteoporosis and bone loss in adult and pediatric hematopoietic cell transplant recipients. Bone Marrow Transplant. 2011 Jan;46(1):1-9.
- Fu JB, Lee J, Smith DW, Guo Y, Bruera E. Return to primary service among bone marrow transplant rehabilitation inpatients: An index for predicting outcomes. Arch Phys Med Rehabil. 94(2):356-61, 2/2013.
- Fu JB, Lee J, Smith DW, Bruera E. Frequency and reasons for return to acute care in patients with leukemia undergoing inpatient rehabilitation: A preliminary report. Am J Phys Med Rehabil. 92(3):215-22, 3/2013.
- Dietz JH. Adaptive rehabilitation of the cancer patient. Curr Probl Cancer. 1980 Nov;5(5):1-56.
- Sabers SR, Kokal JE, Girardi JC, et al. Evaluation of consultation-based rehabilitation for hospitalized cancer patients with functional impairment. Mayo Clin Proc. 1999;74(9):855-861.
- Gamble GL, Gerber LH, Spill GR, Paul KL. The future of cancer rehabilitation: emerging subspecialty. Am J Phys Med Rehabil. 2011;90(5, Suppl 1):S76-87.
Original Version of the Topic
Jack B. Fu, MD, Arash Asher, MD. Rehabilitation management of hematologic malignancies and bone marrow transplant (adults and pediatrics). 07/17/2013.
Jack B. Fu, MD
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Arash Asher, MD
Nothing to Disclose