Acute Lymphoblastic Leukemia Following Hodgkin's Disease

Acute Lymphoblastic Leukemia Following Hodgkin’s Disease

ABDUS SALEEM, M.D.* and ROSALIE L. JOHNSTON, M.D.

Departments of Pathology, Baylor College of Medicine and The Methodist Hospital, Houston, TX 77030

ABSTRACT

Over 100 instances of acute leukemia have been reported in the course of Hodgkin’s disease. The type of leukemia almost always is nonlympho- blastic. Only five well documented cases of acute lymphoblastic leukemia (ALL) have been found by us in the world literature. One case who de veloped ALL six years after intensive radiotherapy for Hodgkin’s disease is herewith reported. The patient responded to treatment with Predisone, Vincristine and intrathecal methotrexate and maintained a complete remis sion on 6-mercaptopurine for nine months. When last seen, the bone marrow revealed a mild increase in blasts indicative of an early relapse.

The incidence of second malignancy cervical area. He was treated initially with developing in the course of Hodgkin’s penicillin but had no significant im disease (HD) has been reported from 1.6 provement. An excisional node biopsy to 2.2 percent.1,13,14 Acute non-lympho- was performed and a diagnosis of blastic leukemias (ANLL) are among the Hodgkin’s disease, mixed cellularity, was commonest second tumors.2,14 There is made. The general architecture of the some controversy in the literature lymph node was partially effaced, though whether acute lymphoblastic leukemia several germinal centers were still pres (ALL) occurs in the course of Hodgkin’s ent. Most of the node consisted of sheets disease.2 A report is presented here of a 35 of lymphocytes with interspersed plasma year old patient who developed ALL six cells, eosinophils and histiocytes. Several years after intensive radiotherapy for HD. atypical histiocytes and Reed-Sternberg cells were identified (figure 1). The pa tient underwent exploratory laparotomy, Case Report splenectomy, open liver biopsy, multiple intraabdominal node biopsies and bone H. F., a 35 year old white male was in marrow biopsy. No other evidence of good health until six years ago when he Hodgkin’s disease was found and the pa noted a small lump in the right anterior tient was classified as clinical stage 1-A. All blood studies were unremarkable. Ex * Address for reprints: Abdus Saleem, M.D., De partment of Pathology, The Methodist Hospital, ternal cobalt radiation therapy delivered Houston, TX 77030. 4,000 rads utilizing the mantel technique. 100 0091-7370/0300-0100 $00.90 © Institute for Clinical Science, Inc. ACUTE LYMPHOBLASTIC LEUKEMIA FOLLOWING HODGKIN’S DISEASE 1 01

The patient was followed for six years and had been asymptomatic and in remis sion until June, 1977 when he became anemic. At this time the patient noted the onset of left flank pain and fever. On ad mission to High Plains Baptist Hospital, the patient was found to have a white blood cell count of 16,300 with 1 percent bands, 11 percent segmented neutrophils, . . . . 21 percent lymphocytes, 1 percent mono cytes and 66 percent blasts. Hemoglobin was 7.9 g, hematocrit was 22 and platelets were within normal limits. Physical examination showed no lymphadenop- athy or hepatomegaly. Numerous lymphoblasts and prolymphocytes were V I ■«* present in the peripheral blood. Bone *VJ marrow aspirate showed a marked prolif eration of lymphocytic precursors. Mega * » H I * * » ■»., - * ^ i karyocytes were adequate. A diagnosis of 1 W -* II acute lymphoblastic leukemia was made • (figure 2). F ig u r e 1. Lymph node biopsy. Normal ar Shortly thereafter, the patient was re chitecture replaced by sheets of lymphocytes, atypi ferred to The Methodist Hospital in Hous cal histiocytes, eosinophils and Reed-Sternbergcell. ton. Repeat bone marrow biopsy was (H&E x 500). hypercellular (95 percent) with approxi mately 67 percent of the population con CBC’s. The patient was readmitted to our sisting of peroxidase and Sudan black B hospital on 9/6/77 because of weakness negative blasts. PAS stain showed an oc casional blast with coarse PAS positive granules. The morphology and cyto chemistry confirmed the diagnosis of acute lymphoblastic leukemia. The patient was given chemotherapy with Vincristine and prednisone for one month. He also received intrathecal methotrexate. On 7/18/77, the bone mar row and peripheral blood showed no in crease in blasts. The patient was felt to be in complete remission. He was started on maintenance chemotherapy with 6-mercaptopurine and was again given intrathecal methotrexate. On discharge, the prednisone was tapered and the pa tient was subsequently maintained on 6-mercaptopurine. Complete blood counts were made at weekly intervals—the patient was fol F ig u r e 2. Lymphoblasts in bone marrow aspi lowed by a hematologist with weekly rate. (Wrights stain X 1250). 1 0 2 SALEEM AND JOHNSTON and weight loss. Admission laboratory ANLL. Only five reported cases of acute data showed a hematocrit of 31, white lymphoblastic leukemia occurring in the blood cells (WBC) 3,000 and 450,000 course of Hodgkin’s disease were found platelets. Bone marrow aspiration and by us.3,7,8,9,10 In reported cases where biopsy showed a hyperplastic marrow ALL occurred simultaneously with HD without any increase in blasts, and the and the cases where a diagnosis of Stem patient was felt to be still in remission. He cell leukemia was made are not included was again discharged on 6-mercapto- in the present study. purine. Bloomfield and Brunning2 in a critical The patient was again seen on 1/3/78 review of English literature reported 17 without complaints and with a hemoglo cases of ANLL. The instances of ALL fol bin of 16, hematocrit of 45, WBC of 6400 lowing Hodgkin’s disease, in their opin with no blasts and platelets of351,000. He ion, were poorly documented and they was noted to have no progressive questioned if ALL ever occurs in the adenopathy or hepatosplenomegaly. The course of HD.2 Both HD and ALL may, at patient was admitted on 12/5/78 to times, present a diagnostic challenge. HD evaluate the state of his leukemia. His may be difficult to differentiate from CBC showed a hematocrit of 41, WBC non-Hodgkin’s lymphoma (NHL), since 5,300 with normal differential, adequate Reed-Stemberg cells have been seen in platelets and no blasts. The bone marrow lymph nodes and bone marrow from pa revealed an orderly myelopoiesis and tients with NHL.6’12'17,18 Moreover, NHL erythropoiesis. Nine percent blast forms frequently peripheralizes into acute were noted which could represent an lymphoblastic leukemia. Thus, in all in early relapse. The patient was given stances of ALL following HD, the diag cytoxan 1000 mg intravenously and was nosis of HD should be reviewed. placed on 4 mg of Decadron twice a day Likewise, it is often difficult to differ for 28 days. He was advised to continue entiate ALL from ANLL by light micros cytoxan at monthly intervals and to report copy alone and ancillary diagnostic to our hospital after three months. studies are necessary in such cases. Cyto chemical stains may provide some help.16 D iscussion In table I are depicted the differential staining characteristics of blasts in acute More than 100 instances of Hodgkin’s leukemias. Typically, the lymphoblasts disease and acute leukemia have been re are peroxidase, Sudan black B and ported in the world literature.2'4,15 In the naphthol AS-D chloracetate esterase majority of patients the type of leukemia is negative. Naphthyl acetate esterase is usually negative but may, rarely, give a faint positive stain. PAS stain is perhaps T A B L E I the most characteristic. In most cases of

Cytochemical Staining of Blasts in Acute Leukemia ALL, at least a few lymphoblasts show a PAS positive (block) cytoplasmic staining. Lympho- Myelo- Mono Terminal deoxynucleotidyl transferase blasts blasts blasts (Tdt) levels are sometimes of great value. This enzyme catalyzes the polymerization Peroxidase Sudan black B of deoxyribonucleotides on the hydroxyl Naphthol AS-D chloracetate ends of oligo or poly deoxyribonucleo esterase Naphthyl acetate esterase ± ++ tides in the absence of a DNA template. PAS + - to + - to + block diffuse diffuse High levels of Tdt have been reported in the cells of some patients with ALL. High ACUTE LYMPHOBLASTIC LEUKEMIA FOLLOWING HODGKIN’S DISEASE 1 0 3

TABLE I I

Acute Lymphoblastic Leukemia (ALL) Following Hodgkin's Disease (HD)

Interval Case Sex & Age Histologic f rom HD from A LL NO. Reference at Onset o f H D Type of HD Therapy to ALL to Death

1 9 F 18 years Mixed cellularity Radiotherapy 2 years 3 months 2 8 M 57 years Not given Radiotherapy 8 years Not given 3 10 Not given Not given Radiotherapy & 6 years Not given chemotherapy 4 3 F 34 years Mixed cellularity Radiotherapy & years 6 weeks chemotherapy 5 7 M 3 years Mixed cellularity Chemotherapy 62$ years 5 months 6 Present report M 29 years Mixed cellularity Radiotherapy 6 years 6 months (living)

levels are found in thymus but very low therapy or both.5 A genetic predisposition levels are seen in normal marrow and in and suppressed immunity may also con other leukemias.11 tribute their share. Rosner and Grunwald15 reviewed four cases of ALL following Hodgkin’s dis Summary ease. Falkson7 reported one case, and our case is added to the list. In table II are A patient who developed Hodgkin’s summarized the salient points of these six disease, mixed cellularity type at the age cases. There are three males, two females of 29 has been described by the present and, in one case, sex is not stated. The authors. He was treated intensively with mean age is 30 years with a range from radiotherapy. Six years later he developed three to 57 years. It is interesting to note acute lymphoblastic leukemia. The blasts that in four cases where microscopic de from his bone marrow and peripheral scription was available, the histological blood, morphologically resembled classification was mixed cellularity type lymphoblasts, were peroxidase, Sudan of HD. Three patients in this series re black B and esterase negative. PAS ceived radiotherapy, one received chemo showed a small population of PAS pos therapy and the other two received both itive block granularity in the cytoplasm. radiotherapy and chemotherapy. ALL de The patient responded to treatment with veloped in these patients from two to prednisone, Vincristine and intrathecal eight years (mean 5.3 years) after the methotrexate and maintained a complete diagnosis of H D . remission with 6-mercaptopurine for nine The relationship between Hodgkin’s months w hen the bone m arrow show ed an disease and acute leukemia (ANLL or early relapse. He was placed on cytoxan at ALL) remains undefined. Whether the monthly intervals and was advised to re disease renders the host more susceptible port in three months for further evalua or the intensive therapy is in some way tion. responsible for the development of sec ond tumor is not entirely clear. Appar R eferences ently there are no characteristic features of Hodgkin’s disease which predispose to 1. B e r g , J. W.: The incidence of multiple primary second malignancy.15 It has been noted cancers. I. Development of further cancers in patients with lymphomas, leukemias, and that the majority of these patients have myeloma. T. Nat. Cancer Inst. 38:741-752, had intensive radiotherapy or chemo 1967. 104 SALEEM AND JOHNSTON

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