So another factor is needed to justify the expansion of the mutated clone.
Toxoplasma could be one of a restricted group of germs capable of jamming some crucial point of the complex immune reaction (involving T-cells, macrophages, complex cytokine interactions) evoked by protozoa and other 'fastidious' germs.
Helicobacter pylori and mycoplasmas might be in the number.
Another 'coincidence' buried in a prestigious
journal like the New England J. of Medicine
ten years ago. Everybody laughs when I say
that the real title should actually be:
"A Mother Nature's Lecture on CML"
Spontaneous remission in a patient with chronic myelogenous leukemia.
Musashi M, Abe S, Yamada T, Tanaka J, Gotohda Y, Maeda S, Sato Y, Morioka M, Sakurada K, Minagawa T, Asaka M, Miyazaki T.
Third Department of Internal Medicine, Sapporo, Japan.
N Engl J Med. 1997 Jan 30;336(5):337-9.
Unfortunately there is no abstract and full-text is not free, but as a
NEJMed subscriber I think I am allowed to write a short summary for you:
A 45-year-old man was referred to our hospital for evaluation of leukocytosis in January 1985. Three months previously, he had reported tarry stools.
A peptic ulcer was diagnosed and treated with intravenous cimetidine. At that time, leukocytosis, thrombocytosis, and anemia were detected. A bone marrow aspirate showed marked myeloid hyperplasia. Cytogenetic analysis revealed Ph-positive cells in the bone marrow, and a diagnosis of CML was made. During the next month the leukocyte count decreased to 14,400 per cubic millimeter, but it subsequently gradually increased to 31,800 per cubic millimeter before admission to our hospital.
Physical examination on admission revealed anemia and mild hepatosplenomegaly. A complete blood count again showed leukocytosis and thrombocytosis. The neutrophil alkaline phosphatase score was 94 (normal range, 170 to 335). Plasma histamine and prostaglandin E concentrations were within the normal range.
An endoscopic examination revealed an ulcer scar in the duodenal bulb.
Regular follow-up, without chemotherapy, was planned for the patient. In February 1985, the hepatosplenomegaly disappeared. The leukocyte count and platelet count returned to normal in April 1985. As of January 30, 1996, the patient had been well, without any signs of recurrence, for 11 years. Blood counts since June 30, 1994, have been normal.
In 1984 the 'infectious theory' of peptic ulcer was still a matter of debate (1).
Consequently the word helicobacter cannot be found through the whole text (but it's a 1997 paper!).
Intravenous cimetidine had been available for several years, and found quite useful for healing peptic ulcers, and probably making life difficult to H. pylori as well.
In the past, cimetidine had been reported to have also an immunomodulating activity.
Something surely happened in that patient during the following weeks and months, and chronic myeloid leukemia (confirmed by more sophisticated tests over the following years) pulled back gently.
Average survival rate for CML was about <5 years then, with 1/3chance to find a donor for BMT.
In 2000 STI571-Gleevec-Imatinib (2pills/day - no BMT) finally came and life became much easier for CML patients. According to some distiguished scientists, this new drug actually represents, in oncology, the most important achievement in the last two decades.
Thanks to Dr. Brian Druker and his colleagues from Oregon.
In 2000 that japanese man just turned 60, hopefully healthy and CML free.
1) click down here for "Helicobacter connection"
Treatment options and outcome from treatment have improved significantly over the years.
Year Treatment Survival (months)
1920-1950 Splenic irradiation 28
1950-1960 Busulfan 35-45
1960-1970 Hydroxyurea 48-67
1970-1980 1st Allogeneic Stem Cell Transplant for CML
1980-1990 IFNa (Interferon alpha) 55-89
1990-2001 IFNa + Cytosine arabinoside (Ara-C)
Recent studies showing significant improvement over IFNa alone
1995-2001 STI-571 >90% 5yrs survival (2007)
Table 1. Treatment options and survival. (JAMA, August 22/29 p. 896)
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