374 Letters and Correspondence

3. Gonaalez-Redondo JM, Sloming TA, Kutlar F, Kutlar A, McKie VC, Huisman C substitution in the donor splice site

4. Huisman THJ: The p- and delta-thalassemia repository. Hemoglobin 16237-258,

5 . Chakraborty R , Kamboh MI, Nwamkwo M, Fernell RE: Caucasian genes in

THJ: Severe Hb S-B"-thalassemia with a T ofthefirstintronofthepglobingene. BrJHaematol71:l 13-117, 1989.

1992.

American blacks: new data. Am J Human Genet 5 0 145-155, 1992.

Acute Lymphocytic Leukemia in Acrodermatitis Enteropathica

To the Editor: Acrodermatitis enteropathica, due to a rare autosomal reces- sive allele, is a disorder in the transport of zinc across the duodenal mucosa [I ,2]. The untreated condition leads to growth delay, neurologic sequelae, intestinal malabsorption, dermatitis, alopecia, dystrophic nails, and death. We report a patient who developed acute lymphoblastic leukemia while being inconsistently treated with zinc

The patient, a 25-year-old man, was born in a rural area 5 hr (by bus) south of Guadalajara, Mexico. His parents were first cousins. A sister died at 8 months with skin lesions and chronic diarrhea. He had red, indurated, and blistering skin lesions beginning in his first month and had had alopecia since infancy. When seen in Los Angeles at age 5 years 7 months, his weight was 14. I kg (50th percentile for 3 years), the height was 87 cm (50th percentile for 2 years), and the head circumference was 48.5 cm (IO-25th percentile). Amphotericin B and topical betamethasone valerate were given for possible chronic mucocutaneous candidiasis, although a skin biopsy showed subacute dermatitis and no organisms. Diiodohydrox- yquinoline also had little effect.

Zinc sulfate (70 mgiday) was started at age 6 years 1 1 months, and the skin lesions greatly improved. The serum zinc level was normal at ages 8 and 10 years, but was low on one occasion at age 11 years (35 p.g/dl; normal 55-150). At age 13 years 3 months, his weight had improved to the 5-10th percentile (35.7 kg), although height was at the 50th percentile for 9.5 years (135 cm). When the patient returned to Mexico at age 14 years, zinc formula was sent from relatives in the United States, but he occasion- ally ran out. When seen at age 15 years after 3 4 months of no zinc, he was despondent and had a red, papular rash around the mouth and eyes. He relapsed again when he ran out of zinc for several months at age 16 years, causing the zinc level to fall to 24 pg/dl. Both episodes reversed with zinc administration. The patient worked on a ranch feeding cows, cutting hay, and fenilizing corn fields near his hometown over the next several years He did not handle pesticides. When he was examined in Los Angeles at ages 18, 19,20, 21, and 24 years, serum zinc levels were 35, 87, 230, 62, and 70 pg/dl, respectively (normal 60-130).

He presented at age 25 years with enlarged cervical lymph nodes, dizzi- ness, epistaxis, and blurred vision. There were chronic hyperpigmentation around the mouth and dystrophic changes of the nails of the hands and feet (Fig. 1). Liver and spleen were enlarged. The hematocrit was 0.153 (nor- mal 0.40-0.49), the hemoglobin was 55 g/liter (normal 139-168), the white blood cell count was 66.2 X IO'iliter (normal 4.0-8.4 X lo9) with 90% blasts, and the platelet count was 22 X IO'/liter (normal 153403 X

lo')). Blasts accounted for 90% of the nucleated cells in the bone marrow, most of which were larger (15-25 pm in diameter) than normal small lymphocytes. Auer rods were not identified, and blasts were negative for Sudan black B stain. Because greater than 10% of the blasts consisted of large cells, the morphologic type was classified as acute lymphoblastic leukemia (ALL), L2, according to the FAB system. Leukemic cells were classified as pre-B cells (TdT, CDlO, HLA-DR, clgM) on the basis of immunohistochemical studies. An attempt before chemotherapy to obtain cytogenetics on bone marrow cells was unsuccessful.

Among adults with acrodermatitis enteropathica, two with cancer have

Fig. 1. The patient at age 25 years. Chronic skin change around the mouth (A) due to episodes of dermatitis. Note dystrophic changes of the nails of the feet (B).

been described. One patient had a dermatofibrosarcoma at age 48 years and a malignant melanoma at age 57 years 131, and the other had a squamous cell carcinoma of the skin at age 30 years 141. Our case is the only known patient with leukemia and acrodetmatitis enteropathica. As a single case, the association could be due to chance. However, zinc has roles in immune function, gene replication, and gene expression 151, so that a link between low zinc and leukemia is plausible. Further repolting would be helpful in assessing the incidence of leukemia in this rare disorder.

HENRY J. LIN EMIL D. KAKKIS

NORA C.J. SUN

STEVEN LIM

ARNOLD W. GUREVITCH

Division of Medical Genetics, Department of Pediatrics,

Department of Pathology,

Division of Hematology,

Department of Medicine, Harbor-UCLA Medical Center, Division of Dermatology, Torrance, California

REFERENCES 1. Danbolt N, Closs K: Akrodermatitis enteropathica. Acta Dern-Venereol Stockh

22: 127-1 69, 1942.

Letters and Correspondence 375

stem cell damage by chemotherapy and bone marrow purging altered the expression of “self’ antigens, and this together with T-cell depletion con- tributed to the development of antiplatelet autoantibody. We believe that immune mechanisms must be studied when isolated and unexpected periph- eral thrombocytopenia is present after autologous bone marrow transplanta- tion or peripheral blood stem cell transplantation.

2. Moynahan W: Acrodematitis enteropathica: A lethal inherited human zinc defi- ciency disorder. Lancet ii:399400, 1974.

3. Shelley WE: Malignant melanoma and dermatofibrosarcoma in a 60-year-old patient with lifelong acrodematitis enteropathica. J Am Acad Dermatol 6:63-66, 1982.

4. Mori 0, Hachisuka H, Kasuda M, Kaji H, Sasai Y : Acrodematitis enteropathica with giant squamous cell carcinomas. J Am Acad Dermatol 23:1174-1175, 1990.

5. Vallee EL, Falchuk KH: The biochemical basis of zinc physiology. Physiol Rev 73:79-118. 1993.

Autoimmune Thrombocytopenia After Autologous Bone Marrow Transplantation

To the Editor: Autoimmune thrombocytopenia has been reported after allogeneic and autologous bone marrow transplantation (BMT and ABMT) [I]. Recently, Colman et al. [2] reported a case of refractory thrombocy- topenia after BMT due to a combination of alloimmunization to HLA antigens and to the presence of an acquired antiplatelet autoantibody. We describe a case of autoimmune thrombocytopenia following ABMT.

A 19-year-old male was diagnosed in October, 1992, with T lymphoblas- tic non-Hodgkin’s lymphoma with a bulky mediastinal mass, pleural and bone marrow infiltration, and a high lactate dehydrogenase (LDH) level. The immunophenotyping of these lymphoblasts showed expression of CD2, CD3, CD4, and CD8 markers. A complete remission (CR) was obtained with a modified LSA,-L, protocol (Memorial Sloan-Kettering Cancer Center Protocol). A long period of aplasia was observed after chemotherapy. The patient had no HLA-compatible sibling, and he re- ceived purged autologous bone marrow with a monoclonal antibody (anti- CD2) and complement, plus peripheral blood stem cells mobilized with recombinant human granulocyte colony-stimulating factor (rH-G-CSF). The conditioning regimen consisted of cyclophosphamide, BCNU, and etoposide (CBV protocol). He received antimicrobial prophylaxis with ciprofloxacin, itraconazol, and acyclovir. Twenty-four hours after infusion of bone marrow, intravenous rH-G-CSF was administered until day 21 posttransplant. Pneumocystis carinii prophylaxis was given with trimethoprimlsulfamethoxazole (TMP/SMX) commencing when there was evidence of neutrophil engraftment and continuing until day 150 posttrans- plant.

The platelet and neutrophil counts fell, reaching 4 X IO’iliter and 0.1 X 10’iliter on days +6 and +8, respectively. Over the 210 days of follow-up, platelet count has been less than 40 X IO’iliter, with engraft- ment of neutrophil and red cells on days +26 and +35 . Infusions of pooled random-donor platelets and random single-donor platelets were adminis- tered until day + I 0 0 in an attempt to keep the platelet count above 20 X IO’iliter. The patient did not experience thrombocytopenia-associ- ated bleeding during the time of follow-up.

On day + 180, 1 month after discontinuing TMP/SMX and without any evidence of lymphoma or viral disease, an investigation for indirect anti- platelet antibody using immunofluorescence antiglobin techniques and di- rect testing utilizing a flow cytometry method showed the presence of an autoantibody of IgG class. No lymphocytotoxic antibodies were detected. A bone marrow examination demonstrated a normal number of megakary- ocytes.

Now, the blood count is as follows: hemoglobin 13 gidl, hematocrit 42.5%, white blood cell (WBC) count 4.0 X IO’iliter with 2.2 X lO’/liter neutrophils, and platelet count 39 X lO’/liter. The patient does not have any clinical manifestation and is not receiving any treatment.

The etiology of formation of autoantibodies after allogeneic or autolo- gous bone marrow transplantation is not well known [ 3 ] . Different mecha- nisms have been postulated: ablative chemoradiotherapy, stem cell damage during in vitro manipulation [4], and immune system imbalance due to inadequate function of certain critical T-suppressor clones [ 5 ] . In our case,

ACKNOWLEDGMENTS

J.A. Garcia Vela was supported by the Asociacion Espafiola Contra El Cancer.

J.A. GARCIA VELA F. ONA

M.C. MONTESERIN A.M. LASTRA

J. GARCIA LARANA J. LOPEZ

J. PEREZ OTEYZA J. ODRIOZOLA

Department of Hematology, Hospitales de Getafe,

Ramon y Cajal, Madrid, Spain

REFERENCES

1. Klumpp TR, Block CC, Caligiuri MA, Rabinowe SN, Soiffer RJ, Rizt J: Immune- mediated cytopenia following bone marrow transplantation: Case report and re- view of the literature. Medicine 7173-83, 1992.

2. Colman RW, Rao AK, Rubin RN: Refractory thrombocytopenia in a 27-year-old female following allogeneic bone marrow transplantation. Am J Hematol 44 :284 288, 1993.

3. Deeg HJ: Delayed complications and long-term effects after bone marrow trans- plantation. Hematol Oncol Clin North Am 454-657, 1990.

4. Minchinton RM, Water AH: Autoimmune thrombocytopenia and neutropenia after bone marrow transplantation. Blood 66:752, 1985.

5. Lum LG: Immune recovery after bone marrow transplantation. Hematol Oncol Clin North Am 4:659-675. 1990.

Successful Treatment of Steroid-Resistant Hemolysis in Chronic Lymphocytic Leukemia With Cyclosporine A

To the Editor: We recently saw two patients with chronic lymphocytic leukemia (CLL) and hemolytic anemia refractory to steroids who were successfully treated with cyclosporine A (CSA) for the hemolytic syndrome as well as for the reduction of the leukemic cell mass.

A 58-year-old male patient with B-CLL had two episodes of Coombs test-positive hemolytic anemia in 6/87 and 2192 that responded well to high-dose steroid treatment. In 8/92 he presented with general weakness, a slight icterus of the sclera, progressive lymphadenopathy, and splenome-

Pathological laboratory data were as follows: leukocytes 45.5 X 1O9/Iiter with 62% lymphocytes and 22% normoblasts in the differential count, reticulocytes 80%, erythrocytes 1.67 X lO”/liter, hematocrit 19%, hemo- globin 68 giliter, platelets 188 X lO’/liter, bilirubin 132 pmoliliter, indi- rect bilirubin 11 8 pmoliliter, haptoglobin <0.05 giliter, lactate dehydroge- nase (LDH) 1,354 Uiliter. The direct Coombs test was strongly positive, and the bone marrow aspirate revealed maximally stimulated erythropoie- sis.

Since treatment with 150 mg prednisolone (2 mglkglday) and a drug trial with cyclophosphamide proved to be ineffective, CSA as another immuno-