HOMEPAGE Resources for SBM

1999 Spring Year2 Case4 - Multiple Myeloma

Case History
Learning Objectives
Web References
Literature References


CASE HISTORY

March 15, 1999

The patient is a 58 year old retired construction worker. He lives in Buffalo with his wife and feels well today.

His illness goes back to May of 1998, while living in Florida, he developed nausea and tiredness. He had taken early retirement in Florida and was on disability because of an injury he received to his back during construction work. The symptoms of tiredness and nausea occurred intermittently but on a daily basis. When he felt nauseated, he would also feel some dizziness. He actually developed some sweats at night where his pillow would be soaked. He has a history of diabetes as well as hypertension but these were well controlled. He was taking glyburide for his diabetes. He would check his glucose levels and they were within the 99-120 range. He did not have any vomiting but he had a few episodes of dry heaves. His bowels were regular. His appetite was good. He had no weight loss but did lose some taste for food. He also developed some numbness and tingling in his feet. In addition, he reports frequent urination, especially at night. He was fairly active but was too fatigued to play golf, which is one of his most favorite activities. He was working part time in a grocery store but had to stop because of these symptoms. These symptoms did not really interfere very much with his lifestyle and he eventually sought medical attention, not because of these symptoms, but because he ran out of his medication. He went to a hospital in Florida. Because he had not been followed there as a patient, there he was referred to the emergency department. He told them about his symptoms and also mentioned that he had had some vague chest pains. He said that as soon as he mentioned the chest pain that they became much more interested and did tests including blood tests and EKG’s. Based on the results of the blood tests, he was told that he would have to be admitted to the hospital. (Although he is not aware of the nature of the blood tests, information from his records reveals that he had renal failure with an elevated creatinine.) He had multiple tests for the first two days in the hospital after which he was told that he had multiple myeloma. He was told that this is a cancer of the bone marrow. A bone marrow test was also done.

Initially when he was told of the diagnosis, he felt, "Why me?" However, he decided to develop a positive attitude and to fight to do as well as he could.

He was begun on chemotherapy. After the first course of chemotherapy he decided to move back to Buffalo where there was family and a better support system. He was seen at several area hospitals He was in the service in 1957 and also in 1968-71 where he was in Viet Nam. He subsequently found out that about 70 people who were in Viet Nam during this time have developed multiple myeloma, which it is felt might be related to Agent Orange exposure. He applied to the VA for disability because of myeloma and was granted 100% disability.

He smoked up to 4 packs of cigarettes a day since age 14. He quit while he was in the hospital. He does not drink alcohol.

When he returned to Buffalo he was continued on chemotherapy. He would receive 96 hours of intravenous chemotherapy through a Mediport implanted on his chest. Following this he would receive 4 days of high dose steroids. This would cause his blood sugar to go very high and he would have to take insulin during this period of time. The chemotherapy resulted in weakness. He lost his sense of taste as well as all his hair. However he says he maintained a very positive attitude that helped a great deal. He felt that all the physicians and nurses caring for him were great and made him feel very comfortable with his treatment. He does recall that sometime during the course of his illness his kidney function was abnormal and that he received some treatment for this. Eventually his kidney function returned to normal.

After 6 months of therapy, he was told that chemotherapy seemed to have some effect but that it would not cure his disease. It was suggested that he have a bone marrow transplant. He was sent to a regional transplant center. He initially received high dose chemotherapy for 2 days after which bone marrow material was harvested intravenously. He then returned home for several weeks. When he returned to the transplant center, he again received chemotherapy and then was given back his own bone marrow again. He was placed on multiple antibiotics to prevent infections. He did not really have any serious complications following his transplant. About 30 days following his transplant his bone marrow was checked again at which time no myeloma was noted. He is now in 100% remission.

At the current time he feels well. He feels his positive attitude has made a large difference. He is going to Florida on vacation for several weeks.

LAB AND CLINICAL INFORMATION

5/98
Seen in Florida. Presented with renal failure with elevated creatinine. IgA monoclonal paraprotein. IgA 2.26 grams/L. Bone marrow - 50-75% involved with pleomorphic plasma cells. Begun on chemotherapy with VAD (vincristine, Adriamycin (doxorubicin) and dexamathasone).
5/26/98
Hypogammaglobulinemia. Decrease in IgA kappa paraprotein. Free kappa light chains present in serum.
5/22/98
Beta2 microglobulin - 3.7
7/27/98
Creatinine 2.2 Beta2 microglobulin - 4.7
8/98
Bone marrow after 3rd cycle: 3-15% plasma cells which stain for monoclonal kappa light chains
9/14/98
Finished 4th cycle of VAD. Bone survey - small lytic lesions in skull and distal right humerus.
Creatinine 1.7 Beta2 microglobulin - 2.9
10/98
Cycle 5 VAD
11/98
Cycle 6 VAD
12/7/98
To transplant center for Bone Marrow Transplant (BMT) evaluation
Bone marrow - moderate plasmacytosis. 1% total cells by flow cytometry CD-38 positive for cytoplasmic kappa chains.
Serum protein electrophoresis- large monoclonal spike obscuring beta region. Little polyclonal staining.
Urine protein electrophoresis - immunoelectrophoresis: Large kappa Bence Jones protein in gamma region.
Quantitative immunoglobulins: IgG 283 IgA 1680 IgM 36 IgD <1.0 IgE <29
Beta2 microglobulin - 2.3
12/10/98
High dose Cytoxan plus GCSF mobilization prior to stem cell harvest.
12/22/98
Stem cell harvest
1/8/99
Admitted for BMT. Received iv Melphalan 1/9-1/10.
1/12/99
Stem cells reinfused - 11.15 x 106 CD34 cells/kg and 1.34 x 108 mononuclear cells/kg.
2/5/99
Bone marrow aspirate/biopsy and flow cytometry - no evidence of myeloma
2/22/99
WBC 9.0 HGB 10.5 Plat 177
Creatinine 1.2 mg/dL (reference range 0.7-1.4)
Glucose 130 mg/dL (70-115)
Protein, total 6.4 g/dL (6.0-8.5)
Albumin 3.5 g/dL (3.5-5.0)
Calcium 9.0 mg/dL (8.5-10.5)
3/99
Consider trial of alpha-interferon
Current post- BMT medications:
Acyclovir
Nystatin swish and swallow
Amoxicillin
Pentamidine inhalation 1/month (rash after Bactrim)


LEARNING OBJECTIVES

Review the histology of bone marrow and of plasma cells.
Review the immunology of immune globulins.

Epidemiology
How common is multiple myeloma in the US?
What is the age and gender of patients with the disease?
Pathogenesis/etiology
Genetic predisposition
Chromosomal abnormalities
Radiation
Role of IL-6
Role of chronic antigenic stimulation
Virus
Clinical manifestations
How often is disease clinically silent?
Physical exam-how useful?
Bone involvement
Renal involvement
Hematologic/coagulation abnormalities
Differential Diagnosis
Monoclonal gammopathy of unknown significance
Other plasma cell diseases
Diagnostic Approach
X-ray studies
Urine findings - Bence Jones proteins etc.
Serum proteins
Staging of disease
Complications
Amyloidosis-which type?
Cryoglobulinemia
Hyperviscosity syndrome
Recurrent infection
Renal failure
Bleeding disorders
Osteolytic bone lesions - role of osteoclastic activating factors
Hypercalcemia
Pathology
Basic lesion is infiltration of bone marrow and other sites by malignant plasma cells.
What is a plasmacytoma?
Renal involvement - Amyloid, pyelonephritis
What is myeloma kidney?
Treatment
Chemotherapy
Bone marrow transplant

WEB REFERENCES

Hematopathology Index
DESCRIPTION:Seventy seven good images. Numbers 59-64 are for multiple myeloma.
URL: http://www-medlib.med.utah.edu/WebPath/HEMEHTML/HEMEIDX.html

Multiple Myeloma - Cornell
DESCRIPTION:Kristen Clark found this. Excellent source. Lecture for 2nd year meds.
Summaries of a number of recent research papers.
URL: HTTP://myeloma.med.cornell.edu

Multiple Myeloma - Hematology
DESCRIPTION:Nice review with some treatment details.
URL: HTTP://www.medstudents.com.br/hemat/hemat6.htm

Multiple Myeloma Treatment with Interferon
DESCRIPTION:A paper analyzing results of several studies on maintenance treatment of multiple myeloma with inteferon.
URL: HTTP://www.medscape.com/adis/CDI/1997/v14.n05/cdi1405.03.trip/cdi1405.03.trip.html

Plasmacytoma, Multiple myeloma 4-345
DESCRIPTION:Radiologic images
URL: http://www.sbu.ac.uk/~dirt/museum/p4-345.html


LITERATURE REFERENCES

Bart Barlogie, M.D., et. al
Plasma Cell Dyscrasias
JAMA, 268: 2947 (1992)

Charles R. J. Singer
ABC of Clinical Haematology: Multiple Myeloma and Reated Conditions
Brit. Med J., 314: 960 (1997)

Michael Hallek, et. al.
Multiple Myeloma: Increasing Evidence for a Multistep Transformation Process
Blood, 91: 3 (1998)

Regis Bataille, M.D., Ph.D. and Jean-Luc Harousseau, M.D.
Multiple Myeloma
NEJM, 336: 1657 (1997)

John A. List, M.D., Ph.D.
The Role of Cytokines in the Pathogenesis of Monoclonal Gammopathies
Mayo Clinic Proceedings, 69: 691 (1994)

James R. Berenson, M.D.
Bisphosphonates in Multiple Myeloma
Cancer, Supplement (Oct 15), 80: 1661 (1997)

Elliott F. Osserman, M.D., et al.
Multiple Myeloma and Related Plasma Cell Dyscrasias
JAMA, 258: 2930 (1987)

Joan Blade, M.D., et al.
Renal Failure in Multiple Myeloma
Arch. Intern. Med., 158: 1889 (1998)

G. David Roodman, M.D., Ph.D.
Mechanisms of Bone Lesions in Multiple Myeloma and Lymphoma
Cancer, Supplement (Oct 15), 80: 1557 (1997)

Raymond Alexanian, M.D. and Meletios Dimopoulos, M.D.
The Treatment of Multiple Myeloma
NEJM, 330: 484 (1994)

Robert A. Kyle, M.D.
Multiple Myeloma
in Conn's Current Therapy - 1998
Ed. by Robert Rakel Saunders, p. 426, 1998