Hematopoietic Precursor Cell Cultures (CFU-C) in Diagnosis and Prognosis of Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML).

Background Diagnosis and prognosis of patients with established MDS/CMML is currently based on WHO criteria and the IPSS prognostic Index. High variation of survival in subgroups warrants the search for additional criteria. A comparison of CFU-C cultures with WHO criteria and IPSS score has not yet been done in a large patient group. Patients and methods We analyzed in a single center retrospective cohort study 93 untreated consecutive patients (55 male/ 38 female; median age: 66 years; range: 13 – 88 years) admitted between July 1992 and June 2002 and diagnosed as MDS/CMML (RA/RARS(4), MDS-U (2), RCMD (26), RAEB I/II (44) and CMML I/II (17). All patients had an unequivocal diagnosis of MDS or CMML according to WHO criteria. Simultaneous examinations of blood, bone marrow (cytology and biopsy), BM-cytogenetics and BM-and PB cultures for CFU-GM and BFU-E were done. Culture results were scored blindly and classified either as “Low risk CFU-C“ including normal growth (N=2), no colony growth (N=6) or reduced growth of normal colonies (N=19) or as „High risk CFU-C’s“ including excess normal growth in PB termed “MPS pattern” (N=5), discrete leukemic cluster growth (N=22), abundant leukemic cluster growth (N=14) or the „CMML pattern“ defined as giant“ pseudonormal“ CFU-GM and strongly reduced BFU-E (N=23). Culture score was compared with the WHO diagnosis and with the IPSS score in all 93 patients and survival was assesed in 82 patients treated with conventional therapy (12 allografted patients were excluded) after minimal observation time of 3 years in July 2005. Results | | Low risk CFU-C score | High risk CFU-C score | |:------------------:| -------------------- | --------------------- | | RA/RARS/RCMD/MDS-U | 15 | 16 | | RAEBI/II | 12 | 30 | | CMML-I/II | | 17 | Comparison of WHO diagnosis with culture score The typical CMML pattern was observed in 13 of 17 patients with CMML (Specificity 94%). | | low risk CFU-C score | low risk CFU-C score | High risk CFU-C score | High risk CFU-C score | |:--------------:| -------------------- | -------------------- | --------------------- | --------------------- | | IPSS Score | alive/dead | mean survival(d) | alive/dead | mean survival(d) | | Low and Int-1 | 4/4 | 2022+/−543 | 8/39 | 965+/−143 | | Int-2 and High | 1/1 | 1024+/−701 | 1/26 | 565+/−92 | Comparison of IPSS Score with culture score Mean survival time for patients with a low/intermediate-1 IPSS score was less than half if they had a high risk CFU-score (p<0.01, ANOVA t-test). For patients with an intermediate-2/high IPSS score the prognostic information gained with the cultures was similar, but low patient number did not permit statistical analysis. Conclusions Hematopoietic precursor cultures yield additional information in patients with MDS / CMML. For diagnosis, CMML has a typical growth pattern, that may help distinction of clonal from reactive monocytosis. For prognosis, the culture pattern adds information to the IPPS score, leukemic growth being strongly predictive of short survival.