BACKGROUND INFORMATION
Multiple Sclerosis is an immune-mediated disease in which a body’s immune system is abnormally responding against the central nervous system (CNS), which consists of the brain, spinal cord, and optic nerves. (1) There are four types of MS: Relapsing-Remitting, Secondary-Progressive, Primary-Progressive, and Progressive-Relapsing. Relapsing-Remitting is the most common form of MS. About 85% of MS patients are initially diagnosed with RRMS (3) These patients experience exacerbations when new symptoms will appear unannounced. (3) With Secondary-Progressive, the current symptoms will worsen over time. (3) Frequently, patients with RRMS will ultimately acquire SPMS. These patients commonly have relapses. (3) A rare form of MS is Primary-Progressive which accounts for about 10% of all MS patients. (3) No relapses occur with this form. Instead, the disease will slowly worsen from initial diagnosis. (3) An extremely rare form of MS includes steadily worsening of disease, acute relapses and no remissions, with or without recovery. (3) Clinically, it is characterized by phases of remissions that ultimately transition into a slow or abrupt (depending on type and condition) disability.
MS is caused by the immune system attacking the myelin sheath, the protective covering of the core of nerve fibers in the CNS and miscommunication between the brain and the rest of the body. T cells move from the bloodstream into the CNS and attack the myelin. (1) Without this “outer-shell,” nerves will become damaged and scar tissue may. When this scar tissue becomes inflamed, lesions form and cause extreme pressure to be put onto nerves. Electrical signals are disrupted when there is no myelin; this causes neurodegeneration. (1) MS is considered a chronic disease meaning it progressively worsens. (2) Progression is the consequence of ongoing inflammatory damage to neurons and axons. More than 2.3 million people are affected by MS worldwide. (1) Women are more likely to develop MS then men due to certain proteins found in the brain. (1) Research shows that genetics increase the risk for developing MS, although environmental factors also increase the risk.
Diagnosis includes blood tests, a spinal tap, and an MRI. Symptoms vary per patient, depending on severity and progression of disease. Some symptoms include vision loss, loss of muscle control, numbness, incontinence, and slurred speech. Treatment may help the symptoms, but the disease is not curable. Researchers argue if there is a distinct treatment, such as high dosage chemotherapy, that can potentially reverse a disability such as MS or can be the initial cause of the degenerative disease.
Methodology
ARTICLE 1: “Multiple Sclerosis and cancer: When two wrongs make a right?” (4)
Researchers reported the case of MM, 14-year-old boy who was diagnosed with MS at 8-years-old and Hodgkin’s lymphoma at 10-years-old. (4) Patient MM, received aggressive immunoablation for approximately six months. (4) Immunoablation uses high-dose chemotherapy. It sequentially destroys the person’s immune system and is then rebuilt with or without hematopoietic stem-cell transplantation. (4)
ARTICLE 2: “Incidence of therapy-related acute leukemia in mitoxantrone-treated multiple sclerosis patients in Germany”
Through a retrospective meta-analysis from six centers, researchers observed six cases of therapy-relayed acute leukemia (TRAL) after the completion of Mitoxantrone in multiple sclerosis patients. (5) Mitoxantrone (MX) is the treatment of aggressive multiple sclerosis (5). Stroet et al., evaluate the incidence of MX-associated TRAL in vast MX-treated patients in a country with high MX usage. (5) Data from six MS centers were analyzed using observation periods beginning between 1993 and 2005 and ending between 2007 and 2010. Continuous variables and dichotomous variables were exhibited. (5) To
summarize individual results, a meta-analysis with effects model was computed. (5) Measures for heterogeneity, the state of being diverse in content were also measured. (5)
FINDINGS & DATA
ARTICLE 1: “Multiple Sclerosis and cancer: When two wrongs make a right?” (4)
After MM received aggressive chemotherapy (immunoblation) for Hodgkin’s lymphoma, his multiple sclerosis symptoms appear to have remitted, the patient has remained progression and disease activity-free for over six years. (4) The low efficacy of immunotherapy in MS has been indicated due to certain immune system cells (T and B cells) being left behind the remind the CNS to start attacking itself again. (4) When patient MM was 8-years-old, his MRI showed white and grey matter called lesions. He was then diagnosed with multiple sclerosis. At age 10, MM was diagnosed with Hodgkin’s lymphoma. He was treated with aggressive chemotherapy for approximately six months, as stated before. Patient MM was immediately treated with steroids, such as prednisone to try to shrink the lesions as much as possible. (4) MM received chemotherapy without HSCT two years after the MS onset to treat a concurrent diagnosis of Hodgkin’s lymphoma. (4) MM’s immune system was able to “rebuild” without the need for HSCT, or any significant infection or malignancy. (4) After chemotherapy, MM initially made physical and cognitive improvements, which has been maintained over a seven-year-period, with no MS relapses or disease activity on an MRI. (4) Prior to immunoablation, and as a result of his MS, MM was wheelchair bound, unable to propel himself, had severe speech difficulties, significantly reduced daily living skills and a documented decline in intellectual functioning. Since chemotherapy, patient MM has shown recovery in multiple areas of daily function. HE can now play sports, take care of personal hygiene and feeding, and his speech has shown significant improvement. (4)
ARTICLE 2: “Incidence of therapy-related acute leukemia in mitoxantrone-treated multiple sclerosis patients in Germany”
With meta-analysis from six data centers, Stroet el al., observed six cases of acute myeloid leukemia (AML). (5) In all of these cases, but one, Mitoxantrone was a potential influencing factor. (5) Between 1990, and 2010, 11 cases of TRAL were reported to the Drug Commission of the German Medical Association. (5) An average of 8.4% of all MS patients were treated with MX and approximately 122,000 MS patients in Germany estimated frequency of TRAL ranges between 0.9% and 0.13%, according to Flachenecker et al. (5) TRAL onset was on average 26.8 months following the completion of MX treatment. (5) Two patients ending in fatalities while four went into remission. (5)
DISCUSSION
ARTICLE 1: “Multiple Sclerosis and cancer: When two wrongs make a right?” (4)
All of patient MM’s medications have were ceased to determine if his MS had actually remitted. (4) Has his MS remitted? Does patient MM have any symptoms at all currently? Anderson et al. did not include these findings. Also, if patient MM’s multiple sclerosis eventually relapses, will a doctor give him chemotherapy for MS if he is cancer free?
Many controversial issues remain; is this ethically right? Particularly in children or individuals who do not currently have cancer and are receiving the treatment solely for MS. Which patients should be chosen for the risky but promising treatment? Hematopoietic stem-cell transplantation (HSCT) involves use of chemotherapy, which is exceptionally expensive. HSCT has been criticized because it involves injecting the patient’s own stem cells taken before immunoablation, resulting in a risk of re-introducing the autoreactive T and B cells back into the patient. (4) This is hypothesized to increase the risk that the MS process will become reactivated, resulting in a patient relapse, which has been observed following HSCT after chemotherapy in MS patients. (4) The alternative approach is to allow the patient to “rebuild” their own immune system endogenously (without HSCT) after chemotherapy, removing the risk of reinfusing autoreactive cells. (4) This approach has been used successfully recently, not only with MS, but also in a variety of other autoimmune conditions. (4)