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Terminal lymphoblastic transformation in polycythemia vera
Terminal Lymphoblastic Transformation in Polycythemia Vera
THEODORE A. BRAICH, M.D. THOMAS M. GROGAN, M.D. MARY J. HICKS, M.D. BERNARD R. GREENBERG, M.D. Tucson,
Arizona
A patient with polycythemia vera and lymphoblastic transformation is discussed. Phenotypic characterization revealed that the predominant leukemic cells were classic “null” lymphoid cells with a minority component of pre-B cells. This case provides evidence that the stem cell disorder in polycythemia vera may involve the lymphocyte early in development. Transformation into acute leukemia appears to be part of the natural history of polycythemia Vera, with an incidence varying from 0 to 50 percent [I]. This leukemia has generally been considered to be of the nonlymphocytic type. It has become apparent that approximately 30 percent of patients with chronic myelogenous leukemia eventually show lymphoblastic transformation [2]. We recently had the opportunity to study a patient with polycythemia Vera whose terminal transformation was lymphoblastic in nature. CASE
From the Section of Hematology/Oncology, Veterans Administration Medical Center, and the Department of Pathology, University of Arizona Health Sciences Center, Tucson, Arizona. Requests for reprints should be addressed to Dr. Bernard Pi. Greenberg, Section of Hematology/Oncology 11 lD, Veterans Administration Medical Center, Tucson, Arizona 85723. Manuscript accepted. October 15, 1984.
304
February 1986
REPORT
Clinical Course. In 1970, at the age of 74, this patient was first noted to have an elevated hemoglobin level. His treatment consisted of only intermittent phlebotomy until 1976 when he was admitted for evaluation. His only symptom then was post-bathing pruritus. Findings on physical examination were unremarkable with the exception of hepatomegaly and splenomegaly. The following laboratory data were obtained: hemoglobin 19.9 g/dl, white blood cell count 15, 100/mm3 (75 percent segmented forms, 12 percent band forms, 7 percent lymphocytes, 3 percent monocytes, 2 percent eosinophils, and 1 percent basophils), and platelet count 1,080,00/mm3. Total blood volume was 86.8 ml/kg, and red blood cell mass was 56.1 ml/kg. Arterial blood gas values were as follows: pH 7.37, oxygen tension 67, carbon dioxide tension 35 (94 percent saturation). The leukocyte alkaline phosphatase score was 190, and the serum BIZ level was 1,500 pg/ml. At that time, he fulfilled the criteria for polycythemia vera developed by the Polycythemia Vera Study Group [3]. Between November 1976 and November 1978, the patient was treated on four separate occasions with phosphorus 32 (total dose 15 mCi). This, combined with intermittent phlebotomy, resulted in good control until September 1980, when a rising platelet count was noted. He then received two weeks of daily busulfan (total dose 112 mg) and two weekly injections of nitrogen mustard (total dose 20 mg). In November 1980, maintenance therapy consisting of monthly courses of chlorambucil was started, but this was discontinued in January 1982 (total dose 560 mg) because of leukopenia. A bone marrow study performed three months later was considered nondiagnostic. The leukopenia persisted, accompanied by a gradual fall in hemoglobin. Bone
The American Journal of Medicine
Volume 80
LYMPHOBLASTiC
TRANSFORMATION
IN POLYCYTHEMIA
VERA-SRAICH
ET AL
Figure 1. Left, the Wright-stained lew kemic cells in the peripheral blood are characterized by high nuclear-to-q& plasmic ratio, one to two nucleoli, and an absence of granules (origlnal magnification X 630, reduced by 20 percent). Right, striking nuclear terminal deoxynu cleotidyl transferase activity is noted in the circulating leukemic blasts (cytocen trifuge preparation of peripheral blood, indirect lmmunofluorescence; original magnification X 1,000, reduced by 20 percent).
marrow study was repeated in July 1982 and revealed total cellularity of 30 percent with 9 percent blasts. The patient subsequently experienced persistent fatigue, weakness, and anorexia. In October 1982, his hemoglobin had fallen to 9.1 g/dl, his platelet count was 74,000/mm3, and his white blood cell count was 38,000/mm3 with 90 percent blasts (Figure 1, left). He was admitted to our hospital but refused any intervention and died shortly thereafter. Morphologic, Immunologic, and Cytochemical Results. The leukemic cells had the morphologic features of lymphoblasts, as shown in Figure 1. These cells had a high nuclear-to-cytoplasmic ratio and one to two prominent nucleoli. Standard indirect immunofluorescent and rosetting methods [4-61 to detect Band T cell markers indicated that the great majority of blasts were terminal deoxynucleotidyl transferase-positive as illustrated (Figure 1, right) (Tdt reagents, Bethesda Research Lab, Bethesda, Maryland). The majority of leukemic cells also demonstrated striking la reactivity (anti-HLA-DR/la-like, Becton Dickinson, Oxnard, California). A minority component (less than 15 percent) was also noted to have cytoplasmic IgM (anti-IgM, Cappel, Cochraneville, Pennsylvania), and the J-5 antibody directed at common acute lymphocytic leukemia antigen was absent (J-5, Coulter Immunology, Hialeah, Florida). Surface immunoglobulin assessment indicated that 1 percent of the cells were surface immunoglobulin-bearing, whereas 3 percent were sheep red blood cell E rosette-positive at 4% (anti-Slg reagents, Cappel, Cochraneville, PA). The cells were also noted to be unreactive with anti-Leu 1 and 4 (Becton Dickinson, Oxnard, CA) precluding a “pre-T” cell proliferation. Sudan black B, chloroacetate esterase, and butyrate esterase stains also gave negative results, helping to exclude myeloblastic and monoblastic differentiation cy-
tochemically. Collectively, the findings indicate a largely “null” lymphoid cell (terminal deoxynucleotidyl transferass-positive, la-positive, common acute lymphocytic leukemia antigen-negative, surface immunoglobulin-negative, T cell-negative) lymphoblastic crisis complicating polycythemia Vera. The occasional cytoplasmic IgM-positive cells indicated a minority component of pre-B cells present. Thus, although much of the “lymphoblastic” transformation was at the near-stem cell level, a portion demonstrated some B cell differentiation, as well described in the blast crisis of chronic myelogenous leukemia.
COMMENTS The similarities between chronic myelogenous leukemia and polycythemia Vera have been appreciated for some time [7]. Attempts to understand the pathophysiology of these two myeloproliferative disorders have been greatly aided in recent years by several important observations. Fialkow et al [8,9], using glucose-6-phosphate dehydrogenase isoenzyme markers, demonstrated that chronic myelogenous leukemia is a clonal disorder involving a multipotential stem cell capable of differentiating into granulocytes, erythrocytes, megakaryocytes, monocytes, macrophages, and some lymphocytes. A clonal origin has also been demonstrated for polycythemia Vera [lo]. Subsequently it has been appreciated that approximately 30 percent of the cases of blastic transformation in chronic myelogenous leukemia are lymphoblastic in origin as determined by morphologic features, presence of terminal deoxynucleotidyl transferase, reaction to acute lym-
February 1986
The American Journal of Medicine
Volume 80
305
LYMPHOBLASTIC
TRANSFORMATION
IN POLYCYTHEMIA
VERA-6RAICH
phocytic leukemia antiserum, and responsiveness to vincristine and prednisone, which are traditionally effective in acute lymphocytic leukemia [2,1 l-141. The phenotype of the lymphoblastic transformation usually is identical to the common type of acute lymphocytic leukemia, i.e. common acute lymphocytic leukemia antigen-positive, lapositive, and terminal deoxynucleotidyl transferase-positive [ 13,161. Further investigations in selected cases of lymphoblastic transformation in chronic myelogenous leukemia revealed a pm-B cell phenotype (common acute lymphocytic leukemia antigen-positive, la-positive, surface immunoglobulin-negative, and cytoplasmic IgMpositive) [ 16,171. There have been two reports of the association of polycythemia Vera and acute lymphocytic leukemia. Hoffman et al [ 181 described a patient with blastic transformation of polycythemia Vera whose blasts were terminal deoxynucleotidyl transferase-positive, but no further characterization was performed. Hann et al [ 191 reported on a child with acute lymphocytic leukemia who had polycy-
ET AL
themia immediately prior to either relapse of previous acute lymphocytic leukemia or the development of a second leukemia. Studies of the leukemic cells from that patient revealed them to be surface immunoglobulin- and sheep erythrocyte receptor-negative; however, a more detailed analysis was not conducted. Our case is unique because detailed phenotyping of the leukemic cells revealed them to be largely classic “null” cell lymphoblasts (terminal deoxynucleotidyl transferasepositive, la-positive, common acute lymphocytic leukemia antigen-negative, surface immunoglobulin-negative, and T cell-negative) with a minority component of cytoplasmic IgM-positive pm-B cells. This observation provides evidence that the stem cell disorder in polycythemia vera may involve the lymphocyte early in development, at the level of the lymphoid stem cell [20] with some B cell differentiation as described in the lymphoblastic crisis of chronic myelogenous leukemia. Further characterization of the leukemic cells in the blastic transformation of polycythemia Vera is clearly warranted.
REFERENCES
2.
3. 4.
5.
6. 7. 8.
9.
10.
11.
366
Landaw SA: Acute leukemia in polycythemia Vera. Semin Hematol 1976; 13: 33-48. Rosenthal S, Canellos GP, DeVita VT, Gralnick HR: Characteristics of blast crisis in chronic granulocytic leukemia. Blood 1977; 49: 705-714. Berlin N: Diagnosis and classification of the polycythemias. Semin Hematol 1975; 12: 339-351. Wirt D, Grogan TM, Payne CM, et al: Phagocytic, lambda light chain, plasma cell myeloma. Am J Clin Pathol 1983; 80: 75-84. Hicks MJ, Jones JF, Thies AC, Minnich LL: The effect of lymphocyte recovery on lymphocyte typing results. Am J Clin Pathol 1981; 76: 745-752. Bollum FJ: Antibody to terminal deoxynucleotidyl transferase. Proc Natl Acad Sci USA 1975; 72: 4119-4122. Dameshek W: Some speculations on the myeloproliferative syndromes. Blood 1951; 6: 372-375. Fialkow PJ, Gartler SM, Yoshida A: Clonal origin of chronic myelocytic leukemia in man. Proc Natl Acad Sci USA 1976; 58: 1468-1471. Fialkow PJ, Denman AM, Jacobson RJ, Lowenthal MN: Chronic myelocytic leukemia: origin of some lymphocytes from leukemic stem cells. J Clin Invest 1978; 62: 815-823. Adamson JW, Fialkow PJ, Murphy S, Prchal JF, Steinmann L: Polycythemia Vera: stem cell and probable clonal origin of the disease. N Engl J Med 1976; 295: 913-916. Savin PS, Anderson PN, Gallo RC: Terminal deoxynucleotidyl transferase activities in human blood leukocytes and lymphoblast cell lines: high levels in lymphoblast cell lines and in blast cells of some patients with chronic myelogenous leukemia in acute phase. Blood 1976; 47:
February
1966
The American
Journal
of Medicine
Volume
12.
13.
14.
15.
16.
17.
18.
19.
20.
60
1 l-20. Greaves MF, Brown G, Rapson NT, Lister TA: Antiserum to acute lymphoblastic leukemia cells. Clin lmmunol Immunopathol 1975; 4: 67-84. Janossy G, Woodruff RK, Peppard MJ, et al: Relation of ‘lymphoid’ phenotype and response to chemotherapy incorporating vincristine-prednisone in the acute phase of Phi positive leukemia. Cancer 1979; 43: 426434. Marks SM, Baltimore D, McCaffrey R: Terminal transferase as a predictor of initial responsiveness to vincristine and prednisone in blastic chronic myelogenous leukemia. N Engl J Med 1978; 298: 812-814. Griffin JD, Todd RF Ill, Ritz J, et al: Differentiation patterns in the blastic phase of chronic myeloid leukemia. Blood 1983; 61: 85-91. LeBien TW, Hozier R, Minowader J, Kersey JH: Origin of chronic myelocytic leukemia in a precursor of pre B lymphocytes. N Engl J Med 1979; 301: 144-147. Vogler LB, Crist VM, Vinson PC: Philadelphia-chromosomepositive pre-B-cell leukemia presenting as blast crisis of chronic myelogenous leukemia. Blood 1979; 54: 1164-l 170. Hoffman R, Estren S, Kopel S, Marks SM, McCaffrey RP: Lymphoblastic-like leukemia transformation of polycythemia Vera. Ann Intern Med 1978; 89: 71. Hann HWL, Fista RS, Rosenstock JG: Polycythemia vera in a child with acute lymphocytic leukemia. Cancer 1979; 43: 1862-1865. Foon KA, Schroff RW, Gale RP: Surface markers on leukemia and lymphoma cells: recent advances. Blood 1982; 60: 1-19.
THEODORE A. BRAICH, M.D. THOMAS M. GROGAN, M.D. MARY J. HICKS, M.D. BERNARD R. GREENBERG, M.D. Tucson,
Arizona
A patient with polycythemia vera and lymphoblastic transformation is discussed. Phenotypic characterization revealed that the predominant leukemic cells were classic “null” lymphoid cells with a minority component of pre-B cells. This case provides evidence that the stem cell disorder in polycythemia vera may involve the lymphocyte early in development. Transformation into acute leukemia appears to be part of the natural history of polycythemia Vera, with an incidence varying from 0 to 50 percent [I]. This leukemia has generally been considered to be of the nonlymphocytic type. It has become apparent that approximately 30 percent of patients with chronic myelogenous leukemia eventually show lymphoblastic transformation [2]. We recently had the opportunity to study a patient with polycythemia Vera whose terminal transformation was lymphoblastic in nature. CASE
From the Section of Hematology/Oncology, Veterans Administration Medical Center, and the Department of Pathology, University of Arizona Health Sciences Center, Tucson, Arizona. Requests for reprints should be addressed to Dr. Bernard Pi. Greenberg, Section of Hematology/Oncology 11 lD, Veterans Administration Medical Center, Tucson, Arizona 85723. Manuscript accepted. October 15, 1984.
304
February 1986
REPORT
Clinical Course. In 1970, at the age of 74, this patient was first noted to have an elevated hemoglobin level. His treatment consisted of only intermittent phlebotomy until 1976 when he was admitted for evaluation. His only symptom then was post-bathing pruritus. Findings on physical examination were unremarkable with the exception of hepatomegaly and splenomegaly. The following laboratory data were obtained: hemoglobin 19.9 g/dl, white blood cell count 15, 100/mm3 (75 percent segmented forms, 12 percent band forms, 7 percent lymphocytes, 3 percent monocytes, 2 percent eosinophils, and 1 percent basophils), and platelet count 1,080,00/mm3. Total blood volume was 86.8 ml/kg, and red blood cell mass was 56.1 ml/kg. Arterial blood gas values were as follows: pH 7.37, oxygen tension 67, carbon dioxide tension 35 (94 percent saturation). The leukocyte alkaline phosphatase score was 190, and the serum BIZ level was 1,500 pg/ml. At that time, he fulfilled the criteria for polycythemia vera developed by the Polycythemia Vera Study Group [3]. Between November 1976 and November 1978, the patient was treated on four separate occasions with phosphorus 32 (total dose 15 mCi). This, combined with intermittent phlebotomy, resulted in good control until September 1980, when a rising platelet count was noted. He then received two weeks of daily busulfan (total dose 112 mg) and two weekly injections of nitrogen mustard (total dose 20 mg). In November 1980, maintenance therapy consisting of monthly courses of chlorambucil was started, but this was discontinued in January 1982 (total dose 560 mg) because of leukopenia. A bone marrow study performed three months later was considered nondiagnostic. The leukopenia persisted, accompanied by a gradual fall in hemoglobin. Bone
The American Journal of Medicine
Volume 80
LYMPHOBLASTiC
TRANSFORMATION
IN POLYCYTHEMIA
VERA-SRAICH
ET AL
Figure 1. Left, the Wright-stained lew kemic cells in the peripheral blood are characterized by high nuclear-to-q& plasmic ratio, one to two nucleoli, and an absence of granules (origlnal magnification X 630, reduced by 20 percent). Right, striking nuclear terminal deoxynu cleotidyl transferase activity is noted in the circulating leukemic blasts (cytocen trifuge preparation of peripheral blood, indirect lmmunofluorescence; original magnification X 1,000, reduced by 20 percent).
marrow study was repeated in July 1982 and revealed total cellularity of 30 percent with 9 percent blasts. The patient subsequently experienced persistent fatigue, weakness, and anorexia. In October 1982, his hemoglobin had fallen to 9.1 g/dl, his platelet count was 74,000/mm3, and his white blood cell count was 38,000/mm3 with 90 percent blasts (Figure 1, left). He was admitted to our hospital but refused any intervention and died shortly thereafter. Morphologic, Immunologic, and Cytochemical Results. The leukemic cells had the morphologic features of lymphoblasts, as shown in Figure 1. These cells had a high nuclear-to-cytoplasmic ratio and one to two prominent nucleoli. Standard indirect immunofluorescent and rosetting methods [4-61 to detect Band T cell markers indicated that the great majority of blasts were terminal deoxynucleotidyl transferase-positive as illustrated (Figure 1, right) (Tdt reagents, Bethesda Research Lab, Bethesda, Maryland). The majority of leukemic cells also demonstrated striking la reactivity (anti-HLA-DR/la-like, Becton Dickinson, Oxnard, California). A minority component (less than 15 percent) was also noted to have cytoplasmic IgM (anti-IgM, Cappel, Cochraneville, Pennsylvania), and the J-5 antibody directed at common acute lymphocytic leukemia antigen was absent (J-5, Coulter Immunology, Hialeah, Florida). Surface immunoglobulin assessment indicated that 1 percent of the cells were surface immunoglobulin-bearing, whereas 3 percent were sheep red blood cell E rosette-positive at 4% (anti-Slg reagents, Cappel, Cochraneville, PA). The cells were also noted to be unreactive with anti-Leu 1 and 4 (Becton Dickinson, Oxnard, CA) precluding a “pre-T” cell proliferation. Sudan black B, chloroacetate esterase, and butyrate esterase stains also gave negative results, helping to exclude myeloblastic and monoblastic differentiation cy-
tochemically. Collectively, the findings indicate a largely “null” lymphoid cell (terminal deoxynucleotidyl transferass-positive, la-positive, common acute lymphocytic leukemia antigen-negative, surface immunoglobulin-negative, T cell-negative) lymphoblastic crisis complicating polycythemia Vera. The occasional cytoplasmic IgM-positive cells indicated a minority component of pre-B cells present. Thus, although much of the “lymphoblastic” transformation was at the near-stem cell level, a portion demonstrated some B cell differentiation, as well described in the blast crisis of chronic myelogenous leukemia.
COMMENTS The similarities between chronic myelogenous leukemia and polycythemia Vera have been appreciated for some time [7]. Attempts to understand the pathophysiology of these two myeloproliferative disorders have been greatly aided in recent years by several important observations. Fialkow et al [8,9], using glucose-6-phosphate dehydrogenase isoenzyme markers, demonstrated that chronic myelogenous leukemia is a clonal disorder involving a multipotential stem cell capable of differentiating into granulocytes, erythrocytes, megakaryocytes, monocytes, macrophages, and some lymphocytes. A clonal origin has also been demonstrated for polycythemia Vera [lo]. Subsequently it has been appreciated that approximately 30 percent of the cases of blastic transformation in chronic myelogenous leukemia are lymphoblastic in origin as determined by morphologic features, presence of terminal deoxynucleotidyl transferase, reaction to acute lym-
February 1986
The American Journal of Medicine
Volume 80
305
LYMPHOBLASTIC
TRANSFORMATION
IN POLYCYTHEMIA
VERA-6RAICH
phocytic leukemia antiserum, and responsiveness to vincristine and prednisone, which are traditionally effective in acute lymphocytic leukemia [2,1 l-141. The phenotype of the lymphoblastic transformation usually is identical to the common type of acute lymphocytic leukemia, i.e. common acute lymphocytic leukemia antigen-positive, lapositive, and terminal deoxynucleotidyl transferase-positive [ 13,161. Further investigations in selected cases of lymphoblastic transformation in chronic myelogenous leukemia revealed a pm-B cell phenotype (common acute lymphocytic leukemia antigen-positive, la-positive, surface immunoglobulin-negative, and cytoplasmic IgMpositive) [ 16,171. There have been two reports of the association of polycythemia Vera and acute lymphocytic leukemia. Hoffman et al [ 181 described a patient with blastic transformation of polycythemia Vera whose blasts were terminal deoxynucleotidyl transferase-positive, but no further characterization was performed. Hann et al [ 191 reported on a child with acute lymphocytic leukemia who had polycy-
ET AL
themia immediately prior to either relapse of previous acute lymphocytic leukemia or the development of a second leukemia. Studies of the leukemic cells from that patient revealed them to be surface immunoglobulin- and sheep erythrocyte receptor-negative; however, a more detailed analysis was not conducted. Our case is unique because detailed phenotyping of the leukemic cells revealed them to be largely classic “null” cell lymphoblasts (terminal deoxynucleotidyl transferasepositive, la-positive, common acute lymphocytic leukemia antigen-negative, surface immunoglobulin-negative, and T cell-negative) with a minority component of cytoplasmic IgM-positive pm-B cells. This observation provides evidence that the stem cell disorder in polycythemia vera may involve the lymphocyte early in development, at the level of the lymphoid stem cell [20] with some B cell differentiation as described in the lymphoblastic crisis of chronic myelogenous leukemia. Further characterization of the leukemic cells in the blastic transformation of polycythemia Vera is clearly warranted.
REFERENCES
2.
3. 4.
5.
6. 7. 8.
9.
10.
11.
366
Landaw SA: Acute leukemia in polycythemia Vera. Semin Hematol 1976; 13: 33-48. Rosenthal S, Canellos GP, DeVita VT, Gralnick HR: Characteristics of blast crisis in chronic granulocytic leukemia. Blood 1977; 49: 705-714. Berlin N: Diagnosis and classification of the polycythemias. Semin Hematol 1975; 12: 339-351. Wirt D, Grogan TM, Payne CM, et al: Phagocytic, lambda light chain, plasma cell myeloma. Am J Clin Pathol 1983; 80: 75-84. Hicks MJ, Jones JF, Thies AC, Minnich LL: The effect of lymphocyte recovery on lymphocyte typing results. Am J Clin Pathol 1981; 76: 745-752. Bollum FJ: Antibody to terminal deoxynucleotidyl transferase. Proc Natl Acad Sci USA 1975; 72: 4119-4122. Dameshek W: Some speculations on the myeloproliferative syndromes. Blood 1951; 6: 372-375. Fialkow PJ, Gartler SM, Yoshida A: Clonal origin of chronic myelocytic leukemia in man. Proc Natl Acad Sci USA 1976; 58: 1468-1471. Fialkow PJ, Denman AM, Jacobson RJ, Lowenthal MN: Chronic myelocytic leukemia: origin of some lymphocytes from leukemic stem cells. J Clin Invest 1978; 62: 815-823. Adamson JW, Fialkow PJ, Murphy S, Prchal JF, Steinmann L: Polycythemia Vera: stem cell and probable clonal origin of the disease. N Engl J Med 1976; 295: 913-916. Savin PS, Anderson PN, Gallo RC: Terminal deoxynucleotidyl transferase activities in human blood leukocytes and lymphoblast cell lines: high levels in lymphoblast cell lines and in blast cells of some patients with chronic myelogenous leukemia in acute phase. Blood 1976; 47:
February
1966
The American
Journal
of Medicine
Volume
12.
13.
14.
15.
16.
17.
18.
19.
20.
60
1 l-20. Greaves MF, Brown G, Rapson NT, Lister TA: Antiserum to acute lymphoblastic leukemia cells. Clin lmmunol Immunopathol 1975; 4: 67-84. Janossy G, Woodruff RK, Peppard MJ, et al: Relation of ‘lymphoid’ phenotype and response to chemotherapy incorporating vincristine-prednisone in the acute phase of Phi positive leukemia. Cancer 1979; 43: 426434. Marks SM, Baltimore D, McCaffrey R: Terminal transferase as a predictor of initial responsiveness to vincristine and prednisone in blastic chronic myelogenous leukemia. N Engl J Med 1978; 298: 812-814. Griffin JD, Todd RF Ill, Ritz J, et al: Differentiation patterns in the blastic phase of chronic myeloid leukemia. Blood 1983; 61: 85-91. LeBien TW, Hozier R, Minowader J, Kersey JH: Origin of chronic myelocytic leukemia in a precursor of pre B lymphocytes. N Engl J Med 1979; 301: 144-147. Vogler LB, Crist VM, Vinson PC: Philadelphia-chromosomepositive pre-B-cell leukemia presenting as blast crisis of chronic myelogenous leukemia. Blood 1979; 54: 1164-l 170. Hoffman R, Estren S, Kopel S, Marks SM, McCaffrey RP: Lymphoblastic-like leukemia transformation of polycythemia Vera. Ann Intern Med 1978; 89: 71. Hann HWL, Fista RS, Rosenstock JG: Polycythemia vera in a child with acute lymphocytic leukemia. Cancer 1979; 43: 1862-1865. Foon KA, Schroff RW, Gale RP: Surface markers on leukemia and lymphoma cells: recent advances. Blood 1982; 60: 1-19.