CORRESPONDENCE

Vance of hygienic care of the arm and the avoidance of particular behaviors. Apart from these comments, we want to applaud Simon and Cody’s effort to underscore the necessity of proper at- tention to a clinical problem which may concern a considerable number of women.

Gianfilippo Bertelli, MD Dario Dini, MD

Gilbert0 G. For-no, MD Albert0 Goxxa, MD

National Institute for Cancer Research,

Genova, Italy 1. Simon MS, Cody RL. Cellulitis after axillary lymph node dissection for carcinoma of the breast. Am J Med. 1992;93:543-548. 2. DeLisa JA, Miller RM, Melnick RR, et al. Re- habilitation of the cancer patient. In: DeVita VT, Hellman S, Rosenberg SA, eds. Cancer-Principles and Practice of Oncology. Philadelphia: JB Lippincott; 1989:2333-2368. 3. Bertelli G, Venturini M, Forno G, et al. An analysis of prognostic factors in response to conservative treatment of postmastectomy lymphedema. Surg Gynecol Obst. 1992;175:455460. 4. Brennan MJ, Weitz J. Lymphedema 30 years after radical mastectomy. Am J Phys Med Rehab. 1992;71:12-14.

Submitted January 4,1993, and accepted April 15, 1993.

PAROXYSMAL NOCTURNAL HEMOGOBINURIA- MARKER FOR CLONAL MYELOPATHY? To the Editor:

The identification by Graham and colleagues’ of patients with paroxys- mal nocturnal hemoglobinuria (PNH) having pre-existing agnogenic my- eloid metaplasia or subsequently de- veloping myelodysplasia is an astute clinical observation. The authors con- elude that the identified PNH defect may represent a marker of the un- derlying myelopathic process and provide a second manifestation of a single stem cell disorder. An alterna- tive mechanism for this association may, however, be proposed.

It is known that the PNH cell pop- ulation is clonal, the concomitant anomalies in multiple cell lines argue for a somatic mutation in a multipo- tent stem cell. As the PNH clone must

have grown from a single cell to a large population of the marrow out- put, it would appear to have a growth advantage; conversely, the suscepti- bility of PNH cells to complement-in- duced lysis must certainly place them at a disadvantage. A possible expla- nation for this paradox is that the growth advantage may be relative rather than absolute, implying that the PNH clone may grow to a clini- cally relevant size only when normal hematopoietic cells are themselves not growing normally.z Indeed, it has been suggested that small PNH clones are common in normal peo- ple.3 In both agnogenic myeloid meta- plasia and myelodysplasia the major specific pathophysiologic mecha- nism is ineffective hemopoiesis, in- cluding a decreased proportion of cells in the deoxyribonucleic acid (DNA) synthesis phase of the mitotic cycle and an increased death frac- tion.4 This means that the nonmalig- nant PNH clone may serve as a marker, not of a single stem cell dis- order, but of abnormal maturation of coexistig marrow cells.

Perhaps future synthesis and mat- uration analysis of “non-Pm ery- throid colonies in the bone marrow may provide further insight into the interesting association demonstrat- ed by the authors.

Ajay Anand, MD Nassau County Medical Center

East Meadow, New York

1. Graham DL, Gastineau DA. Paroxysmal nocturnal hemoglobinuria as a marker for clonal myelopathy. Am J Med. 1992;93:671-674. 2. Editorial. Paroxysmal nocturnal hemoglobinuria. Lancet. 1992;339:395-396, 3. Dacie JV. Paroxysmal nocturnal hemoglobinuria. Sangre. 1980;25:890-895. 4. Golde DW, Cline MJ. Human preleukemia- identification of a maturation defect in vitro. NEJM. 1973;288:1983.

Submitted December 29,1992, and accepted March 26, 1993.

The Reply: We appreciate the comments by

Dr. Ajay Anand regarding our de- scription of patients with paroxys- mal nocturnal hemoglobinuria (PNH) co-existing with either agno- genie myeloid metaplasia (AMM) or

myelodysplasia (MDS). Dr. Anand suggests that a possible alternate mechanism for this association is that these patients have a second clonal disorder leading to a relative growth advantage for the marrow population exhibiting the PNH de- fect and its subsequent co-expres- sion as a clinical disorder.

This is an intriguing hypothesis but requires that each individual have defects in two separate stem cell lines. Proving or disproving this hypothesis is difficult given the ret- rospective data we presented. Sev- eral methods may be considered to test this theorem.

Our findings of a 19% (g/47) oc- currence of PNH with either AMM or MDS is higher than would be ex- pected coincidentally. The precise incidence of MDS and AMM is diffi- cult to define, but the prevalence of PNH would have to approach 19% to be only coincidental.

In general, chromosomal markers specific for PNH have not been iden- tified. Teyssier et al2 performed serial ehromosomal analyses on a patient with PNH and MDS who subse- quently developed acute megakary- oblastic leukemia (AMkL). This pa- tient developed MDS 3 months after the diagnosis of PNH. Chromosomal analysis at the time of diagnosis with MDS revealed a trisomy 9 which re- mained through the time of transfor- mation to AMkL. Only one karyotype was identified at the diagnosis of MDS. In our series of 5 patients with MDS and PNH, 3 had a ehromosomal analysis performed at the time of di- agnosis with MDS. Two of 3 exhib- ited a single karyotypically identifi- able clone while the third had 2 populations (46,XY/47,XYY). This would argue against 2 separate stem cell populations with disparate ab- normalities being present.

Decay accelerating factor (DAF) has been shown to be lacking in the abnormal cells of patients with PNH.S Devine et al4 analyzed the mar-

row blasts of a patient with PNH who developed acute myeloblastic leukemia (AML). Only 3% of the mar-

August 1994 The American Journal of Medicine@ Volume 97 203