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While acute pancreatitis is a recognized complication of numerous drugs, cytarabine's role in causing this complication is controversial. Approximately 15 cases have been reported to the Food and Drug Administration linking cytarabine with pancreas-related toxicities. Previous case reports have been complicated by comorbid illnesses and the coadministration of other drugs associated with acute pancreatitis.This report describes the clinical course of a patient with acute myelogenous leukemia (AML) who developed recurrent pancreatitis associated with cytarabine therapy.A male age 36 years with French-American-British M5B acute myelogenous leukemia received induction cytarabine (200 mg/m2/day) by continuous infusion for 7 days, and subsequently developed acute pancreatitis. The patient was rechallenged with intermittent, bolus, high dose cytarabine (HDAC) (3 g/m2bid administered over 3 hours) during the following intensification treatment, but did not develop clinical acute pancreatitis. Retreatment with continuous infusion cytarabine at a later time resulted in recurrence of acute pancreatitis.This case illustrates that cytarabine treatment may cause acute pancreatitis, and that this toxicity may be schedule dependent. In those with known sensitivity to cytarabine, altering the administration technique may avoid this complication.

Langerhans cell precursors are considered to be identical to their mature counterparts except for the lack of Birbeck granules. Proliferations composed of such histiocytes appear to be uncommon.Standard immunophenotypic, molecular genetic, and DNA content studies were used to characterize various hematopoietic disorders, including a proliferation of precursor Langerhans cells, which arose sequentially in a patient.The patient studied initially had a low-grade, B-cell, non-Hodgkin lymphoma and subsequently had an unusual histiocytic proliferation (precursor Langerhans cell histiocytosis) in cutaneous and lymph node sites. The patient eventually died of acute myelogenous leukemia (FAB, M5).A larger series is required to determine the significance of the precursor Langerhans cell phenotype, particularly with respect to the development of acute myelogenous leukemia.

Background. To study the correlation of environmental exposure to potentially mutagenic agents and the clinicopathologic picture in acute myeloid leukemia (AML), clinical features, morphologic characteristics, immuno-phenotype, and cytogenetics were studied in 59 patients with newly diagnosed AML. Methods. Based on interviews on occupational hazards and hobbies showing prolonged contact with pesticides (18 patients) and organic solvents (7 patients), 25 patients were categorized as “exposed.” Thirty-four patients were categorized as “unexposed,” based on anamnestic findings. Results. Light microscopic studies showed myelodysplasia involving multiple cell lineages in all assessable patients with professional exposure to pesticides and organic solvents, whereas morphologic aberrations of the non-blast cell population were confined to a minority of cells in unexposed patients. These findings were confirmed by electron microscopic studies in 31 patients. Immunologic analysis showed the presence of a minor megakaryoblastic component in six exposed patients and showed positive findings for the CD34 stem cell marker in 85% of exposed patients, a figure significantly higher as compared with that for unexposed subjects. Cytogenetic studies confirmed the frequent occurrence of 5q and/or 7q aberrations in patients occupationally exposed (10 of 25 cases). Other recurring chromosome aberrations in the exposed group were 17p-, trisomy 11q, and trans-location of 16q, 6p, 7p, and 11p, whereas the classic AML-specific translocations (i.e., t[15;17]; t[8;21]) were detected only in unexposed subjects. Conventional chemotherapy achieved complete remission in 1 of 19 exposed patients, as opposed to 14 of 29 unexposed patients, with a median survival of 2 months in the former group and 8 months in the latter. Conclusions. Taken together, these findings document that AML in patients professionally exposed to toxic substances may represent a distinct cytogenetic and clinicopathologic entity. The clinicobiologic characteristics in these exposed patients are similar to the features of AML arising in patients with prior chemotherapy for another tumor, thus suggesting that similar transformation pathways may underlie leukemogenesis induced by cytotoxic drugs and by environmental exposure to some pesticides or organic solvents. Cancer 1992; 70:77–85.

Hematopoietic and lymphoproliferative cancer risk among the 3.7 million United States male veterans who use the Veterans Administration (VA) medical system annually was assessed using age-specific incidence curves and cumulative incidence rates. Relative risk comparing the VA with general population risk estimates from the Surveillance, Epidemiology, and End Results (SEER) data were increased significantly for all malignancies examined. The VA sample showed risk increases of 93% for Hodgkin's disease, 20% for non-Hodgkin's lymphomas, 51% for multiple myelomas, and 40% for all leukemias. Among the leukemia subtypes, the observed risk increases were 54%, 23%, 80%, and 46% for lymphocytic, granulocytic, monocytic, and other forms of leukemia, respectively. The large size of the sample and the consistency of risk estimates with two different methods confer validity and strength to these findings. The possible relevance of the high prevalence of tobacco and alcohol use in this population sample to the current findings is discussed and the need for further analytic investigations to explain the increases in risk is emphasized.

Thirty-seven children and adults who developed acute nonlymphocytic leukemia after the administration of chemotherapy that included etoposide or teniposide for a variety of hematologic and solid malignancies were identified. The secondary leukemia that occurred in these patients could be distinguished from the secondary leukemia that occurs after treatment with alkylating agents by the following: a shorter latency period; a predominance of monocytic or myelomonocytic features; and frequent cytogenetic abnormalities involving 11q23. Patients receiving an epipodophyllotoxin are at risk for developing secondary leukemia that has features distinct from the syndrome of secondary leukemia associated with alkylating agents.

The need for prophylactic therapy of the central nervous system in adult acute nonlymphoblastic leukemia has been suggested but no proven. Over a 4-year period from January 1973, to December 1976, we have maintained 40 patients achieving complete remission on a regimen consisting of monthly courses of Cytosine Arabinoside and 6-thioguanine. Twenty patients remain in remission with a predicted median remission duration for the entire group of 14.5 months. Thirty nine of the patients did not have central nervous system leukemia at diagnosis, and only one of these patients (2.6%) has had remission tenance regimen there is little need for central nervous system prophylaxis in adult acute nonlymphoblastic leukemia.

Ferritin was purified from acute monocytic leukemia cells, and its biochemical and immunological properties were investigated. The iron content of acute monocytic leukemia cell ferritin was extremely low, and this ferritin migrated slightly faster than normal adult liver ferritin on immunoelectrophoresis and polyacrylamide gel disc electrophoresis. Isoelectric focusing in polyacrylamide gel showed predominantly acidic isoferritins. This was considered to characterize the nature of isoferritin from normal monocytes or to be the result of neoplastic change of monocytes. Immunologic studies failed to recognized any antigenic differences between isoferritin from acute monocytic leukemia cells and that from normal adult liver. Therefore, selective quantitation of acute monocytic leukemia cell isoferritin, if any in leukemic sera, by means of immunoassay was considered difficult.

Cytogenetic studies have been done on a group of childhood patients over a period of 3 1/2 years in which time Giemsa trypsin banding was applied to all specimens. Fifteen of the 107 patients (14%) were diagnosed as having acute nonlymphoblastic leukemia (ANLL). Twelve of the 15 had chromosomal abnormalities. The most common was an involvement of the No. 7 chromosome which occurred in five patients. Three patients had trisomy 19. No correlation could be found between the disease subgroup and the karyotypic aberration in patients with anomalies involving a common chromosome.

The concentration of ferritin in serum and leukemic blasts were measured with the improved method of enzyme immunoassay for ferritin which uses beta-D-galactosidase from Escherichia coli. Precise measurement of ferritin was possible for concentration as low as 0.2 ng/ml serum. A good correlation (correlation coefficient, 0.946) existed between the ferritin radioimmunoassay and enzyme immunoassay. The serum ferritin levels in healthy males were 97.2 +/- 46.7 ng/ml, whereas those in healthy females were 53.5 +/- 27.1 ng/ml. Serum ferritin level was markedly increased (698 +/- 447 ng/ml) in sera of 36 patients with various types of acute leukemia, of which acute monocytic leukemia showed the highest serum ferritin concentrations (1156 +/- 324 ng/ml). Leukemic blasts from 24 patients with acute leukemia contained markedly elevated concentrations of ferritin (64.3 +/- 38.7 ng/10(6) cells) as compared with the ferritin concentration in normal leukocytes (7.1 +/- 2.8 ng/10(6) cells). The blasts cells from the patients with acute monocytic leukemia showed the highest ferritin levels (105 +/- 26.6 ng/10(6) cells).

Fibrinogen survival using 125I-labelled homologous fibrinogen was studied in 17 adults with acute leukemia. Five patients in complete remission had normal fibrinogen survival and turnover rate. Five of 6 patients undergoing induction therapy and 4 of 6 in relapse had shortened fibrinogen survival; the turnover rate was increased in all 12 patients. Nine of 12 patients with active disease had elevated levels of fibrinogen degradation products in the serum. Serial coagulation studies did not support the diagnosis of overt disseminated intravascular coagulation. There was no correlation between the morphological type of leukemia, chemotherapy, the presence of fever and sepsis, or liver dysfunction and fibrinogen survival. Other possible causes of the accelerated fibrinogen turnover in patients with active disease are discussed.

The phagocytic potential of leukemic cells in various types of acute leukemia was studied. Cases included lymphoblastic leukemia, myeloblastic leukemia, myelomonocytic leukemia, monocytic leukemia, progranulocytic leukemia, blast transformation of chronic myelocytic leukemia, and unclassified leukemias. Cytochemical stains were used as an aid in classification. These included Sudan black B, naphthol AS-D chloroacetate esterase, alpha-naphthyl butyrate esterase, acid phosphatase, and periodic acid-Schiff. Phagocytosis was evaluated after incubation of leukemic cells with Candida albicans. Rare phogocytic activity was seen in lymphoblastic leukemia, unclassified leukemias, blast crises in chronic myelocytic leukemia, and progranulocytic leukemia. Myeloblastic leukemias were feebly phagocytic. Myelomonocytic leukemia and monocytic leukemia both exhibited marked phagocytosis which distinguished them from the other acute leukemias. Myelomonocytic leukemia could be differentiated from acute monocytic leukemia by its greater phagocytic capacity.

Rubidazone was used as sole chemotherapy in 170 adults and children with acute leukemia and sarcoma. When rubidazone was employed to treat the first attack, complete remission was achieved in : 1) 40 out of 70 patients (57%) with AML; 2) two out of six patients with AML where previous chemotherapy had failed; 3) four out of five patients with ALL; 4) 12 out of 14 patients with acute monoblastic leukemia. When used to treat relapse, rubidazone produced complete remission in : 1) 14 out of 31 cases of AML; 2) 18 out of 39 cases of ALL; 3) 2 out of 3 cases of non-Hodgkin lymphoma. Treatment of a case of rhabdomyosarcoma was unsuccessful. In the treatment of acute myeloblastic and monoblastic leukemias, it may be concluded that rubidazone induces a higher rate of complete remission than any other previously reported drug which was used alone. It also achieves remission rates similar to those resulting from a combination of daunorubicin and Ara-C. Furthermore, when compared with daunorubicin, rubidazone allows better control of the induction of aplasia.

In a series of 130 cases of acute leukemia studied by cytochemical staining techniques, 10 cases cytochemically diagnosed as "pure" monocytic leukemia were seen. Cytochemical staining of bone marrow aspirates from these patients revealed all leukemic cells to be Sudan black negative. No positive reactions were observed for peroxidase or naphthol AS-D chloroacetate esterase. All cases demonstrated strong alpha-naphthyl acetate esterase positivity; and fluoride-inhibited naphthol AS-D acetate esterase positivity was observed in 8 of 9 cases tested. The P.A.S. reaction showed diffuse fine to coarse granules. Oil red O stain was positive in 8 of 9 cases, and the beta-glucuronidase activity was strong in 5 of 9 cases. Light microscopy revealed cells with monocytic or histiocytic morphology. Electron microscopic studies in 2 cases demonstrated features consistent with leukemic monocytic or histiocytic morphology; none was suggestive of granulocytic or lymphocytic leukemia. Five of 6 patients treated with drug regimens including prednisone and vincristine entered a complete remission; the other obtained a partial remission. Two patients achieved complete remission after treatment with Adriamycin, 1 following a relapse. Three patients who received cytosine arabinoside as their only therapy died soon after treatment was commenced. It is suggested that the cytochemical similarity but morphological differences in those patients may be objectively used to group them as cases of histiomonocytic leukemia.

There were 294 children with acute myelogenous leukemia (AML) entered into the German AML Berlin, Frankfurt, and Munster hospitals (BFM) 78 and 83 studies. Thirty (10%) died as a result of hemorrhage and/or leukostasis prior to or in the first 12 days of therapy. The risk of early death due to hemorrhage and/or leukostasis is significantly greater when certain features are initially present: acute monocytic leukemia (French-American-British [FAB] M5), hyperleukocytosis (greater than or equal to 100,000/microliter), and extramedullary organ involvement (P less than 0.001). The risk increases sharply when these factors exist in combination: 72% mortality with FAB M5 and hyperleukocytosis, and 43% with FAB M5 and extramedullary organ involvement. In 11 patients leukostasis alone or in combination with hemorrhage was probably the cause of death during the first 3 days after diagnosis. All 11 children presented with hyperleukocytosis and were classified as monocytic subtype FAB M4 or M5. After induction, a close temporal association between rapid blast reduction and occurrence of fatal hemorrhage was established in five patients. Thrombocytopenic hemorrhages were controllable and, therefore, responsible for death only in exceptional cases. It is difficult to avoid these early fatal complications with current therapeutic measures. Early exchange transfusion together with special supportive care may be useful.

A patient with nonfamilial peripheral neurofibromatosis (NF) (von Recklinghausen's disease) is reported who contracted acute monocytic leukemia at 60 years of age. In the course of the illness, myelonecrosis developed and the patient died 4 months later due to a therapy-resistant bone marrow relapse. This association of the two illnesses would appear to confirm reports on an increased incidence of nonlymphatic leukemia and NF. Such an association is seen during childhood as juvenile chronic leukemia, but it is uncommon in adulthood.

Ricinus communis agglutinin (RCA) staining of malignant histiocytosis (two cases) and tissue infiltrates of monoblastic leukemia revealed two distinct macrophage-histiocyte types: one with cytoplasmic staining (RCA+), the other without (RCA-). RCA+ cells corresponded to benign-appearing histiocytes without nuclear atypia, whereas RCA-cells were cytologically malignant. In one case of malignant histiocytosis, many RCA-tumor cells were surrounded by a thin cytoplasmic extension of RCA+ cells, which suggested an interaction between the tumor cells and stromal macrophage-histiocytes. These observations support the view that most benign-appearing histiocytes in malignant histiocytosis are reactive in nature and suggest that RCA staining can be useful in distinguishing between benign and malignant disorders of macrophage-histiocytes.

A multidisciplinary methodology was applied to study 6 patients with acute leukemia (AL) following treatment for Hodgkin's disease. All 6 patients developed acute monocytic leukemia according to cytochemical criteria; morphologically, 3 cases were undifferentiated monoblastic leukemia; 3 cases were partially differentiated monocytic leukemia. In 3 of the 6 cases, cell suspensions from peripheral blood and/or bone marrow bore predominantly surface receptors for the Fc fragment of IgG and/or C-3 fraction of complement and exhibited variable degrees of phagocytosis. Two cases lacked any recognizable membrane markers or phagocytic activity. Terminal transferase enzymatic activity was not diagnostically elevated. Soft agar bone marrow culture studies revealed no growth or a characteristic leukemic cluster pattern. Chromosome analysis done in 1 of the 2 patients studied revealed hypodiploidy and structural rearrangement. Prospective studies, done serially, will help determine whether development of AL in patients with Hodgkin's disease results from the influence of intensive and potentially oncogenic therapy or represents progression from a preleukemic stage inherent to the original tumor.

Two children with leukemia are presented, each demonstrating an unusual aspect of anthracycline-induced cardiomyopathy. In the first patient (a 7-month-old female with acute monocytic leukemia) extremely young age and previous chemotherapy with a podophyllotoxin derivative, VP-16, may have prediposed the patient to fatal congestive heart failure at a total Daunorubicin dose of only 225 mg/m2. In the second patient, a delay of 4 1/2 years was not sufficient in preventing congestive heart failure resulting from the administration of additional anthracycline chemotherapy. We conclude that extremely young age and, possibly, prior therapy with VP-16 may be addition risk factors in the development of anthracycline cardiomyopathy. Also, we suggest that once an anthracycline agent has reached a toxic threshold for the myocardium, the heart may always be at risk to injury from additional Adriamycin or Daunorubicin therapy.

The peripheral blood of 2 patients with acute monocytic leukemia of the undifferentiated type was studied for the presence of leukemic progenitor cells in colony forming assays. The peripheral blood of both patients contained only one type of progenitor cell as determined with these assay systems. Daughter cells of these progenitor cells morphologically and histochemically resembled monoblasts and immature macrophages. Similar progenitor cells were not encountered in the study of 5 patients with acute myelogenous leukemia whose peripheral blood cells formed colonies in the same system. The finding of this unusual progenitor cell supports the existence of acute monocytic leukemia as a separate clinicopathologic entity, and suggests that it represents a malignant transformation of a progenitor cell of the monocyte/macrophage series. An alternative explanation of these observations would be provided by single phenotypic expressions of a multi-potent stem cell which has undergone malignant transformation.

Qualitative and quantitative ultrastructural studies were performed on mitochondria of leukemic monoblasts from 15 patients with acute monoblastic leukemia. Similar comparative observations were made on mitochondria of myeloblasts from 14 hematologically normal controls. No significant quantitative differences were noted between normal and leukemic mitochondria. Area measurements were approximately equal. Qualitative differences between the two groups consisted of increased numbers of irregularly shaped mitochondria, damaged mitochondrial membranes, mitochondria with damaged matrix, and small granules in mitochondria in the leukemic group. Leukemic cells exhibited nuclear-mitochondrial contact and virus-like particles within damaged mitochondria. To confirm the presence of virus-like particles and to aid in our understanding of nuclear-mitochondrial interaction, a C-type virus producer MSV-MLV infected rat embryo cell culture was used for additional analysis. Mitochondrial abnormalities and increased frequency of virus in damaged mitochondria, often attached to mitochondrial membranes, were noted. Several lysosomes exhibited accumulations of virus and budding into lysosomes from lysosomal membranes. Mitochondria are important organelles in glycolytic-oxidative phosphorylation pathways, and carry extranuclear genetic information. Further studies of morphologic and biochemical abnormalities of leukemic mitochondria and the interaction between the mitochondria and the nuclei in leukemic cells are needed to provide researchers with data on extranuclear factors operating in oncogenesis.

A 7-year-old boy with acute monocytic leukemia (AMoL) had leukemic monocytes that formed spontaneous rosettes with sheep red blood cells (E-rosette). The E-rosette formation was observed in 75% of leukemic monocytes at 4 C and in 37% at 37 C. Cytochemical and ultrastructural studies confirmed that the rosette-forming cells were leukemic monocytes. The leukemic monocytes attached to the red blood cells at a portion of their surface and did not show any phagocytic processes at the electron microscopic level. The data from this patient seem to indicate that in a rare case of AMoL, abnormal myeloid lymphoid stem cells can differentiate to monocytes while retaining lymphoid properties.

Three patients were studied: two infants with acute monocytic leukemia who failed to respond to the initial combination therapy of daunorubicin with cytosine arabinoside, and an adolescent with relapsed acute monocytic leukemia. They were intensively treated with epipodophyllotoxin (VP-16-213) alone and subsequently had complete remission. One patient showed apparently dose-dependent cytotoxic effect. All three patients have maintained complete remission for 6, 7, and 11 months, respectively. Toxicities, including myelosuppression, alopecia, nausea, vomiting, and renal dysfunction, were well tolerated. Intensive treatment with VP-16-213 alone was thus found to have a potent therapeutic effect on acute monocytic leukemia in children. VP-16-213 deserves a further assessment in the therapeutic protocol for patients with childhood acute monocytic leukemia.

Three siblings with a lifelong history of a bleeding disorder and thrombocytopenia died from a myeloproliferative disease. In 2, the terminal event resembled juvenile chronic myelogenous leukemia, and in the third, the diagnosis was acute monocytic leukemia. A family study revealed that the mother and 5 other siblings had a variety of hematologic abnormalities. These included chronic thrombocytopenia, abnormal platelet function, elevated concentrations of HgbF or serum vitamin B12, and low leukocyte alkaline phosphatase (LAP) scores either singly or in combination. At the time of study, none had evidence of malignancy. Members of this family have a myeloproliferative disorder that has the potential for terminating in nonlymphocytic leukemia, a combination of events which appears not to have been reported previously.

The effect of immunotherapy with Nocardia rubra cell-wall skeleton (N-CWS) on remission duration and survival of adults with acute myelogenous leukemia (AML) was studied in a prospective randomized controlled study. After having been induced into complete remission and having been consolidated, 73 patients were randomized either to maintenance chemotherapy or maintenance chemotherapy plus immunotherapy with N-CWS and irradiated allogeneic AML cells. Thirty-four patients in the chemotherapy group and 32 in the chemoimmunotherapy group were evaluable. Six months after the closure of the study, the immunotherapy showed a borderline beneficial effect on remission duration (P = 0.080) and on survival length (P = 0.098). When the data were analyzed at 30 months after the entry, there was a borderline significant difference in remission duration (P = 0.080) between the two groups, prolonging the 50% remission period by 110 days; but no significant difference in survival length (P = 0.314), although the 50% survival was 168 days longer in the chemoimmunotherapy group. However, there were 4 (18.2%) 5-year relapse-free survivors among 22 patients (11 in each group) who had been diagnosed more than 5 years before the time of the present analysis, and all of them belonged to the chemoimmunotherapy group (P = 0.090). Thus, immunotherapy with N-CWS and irradiated allogeneic AML cells seems to be active in the treatment of adult AML when used for maintenance therapy in combination with chemotherapy.

An infant with acute monoblastic leukemia who presented with an extramedullary mass and involvement of the bone marrow, cerebrospinal fluid, and skin is described. After achieving remission, she later developed a relapse that was isolated in the skin. Superficial electron beam irradiation to the total skin surface was administered as therapy for the relapse. She remains in remission 12 months following this treatment. The isolated nature of the skin relapse, in addition to the fact that the relapse did not involve a previously irradiated field, suggests that the skin may have harbored the leukemic cells since the time of diagnosis. Cytogenetic data is presented that lends further support to this hypothesis.

Improvement in the management of acute leukemia in adults has not progressed nearly so rapidly as has the treatment of childhood leukemia. One important difference is that most adults have myeloblastic or related forms of the disease (AML), whereas the majority of children have lymphoblastic leukemia (ALL). However, even adults with ALL fail to respond as well to a similar regimen as do children with the same type of leukemia. In a recent series of patients with ALL who were treated with the complex multiple drug "L-2" protocol, the incidence of complete remission in adults was 78% vs. 99% in children, and the median duration of remission was only 24 months in the adults, whereas it has not yet been reached in the children and is projected to be over 4 years. In AML and the related nonlymphoblastic forms of acute leukemia, therapy is still unsatisfactory in both adults and children. With the best current drug treatment schedules, the incidence of complete remission is now better than 50%, but it is often difficult to compare the exact remission rates in different series because of differences in reporting results. In adults treated with the multiple drug "L-6" protocol, the incidence of remission in previously untreated patients was 56% and the median duration of remission was 10 months. The median survival of all patients (responders and non-responders) was 1 year whereas that of responders only was 2 years. It is encouraging that a significant proportion of those patients with AML who have complete remissions now remain in remission for extended periods; about 45% of patients responding to the "L-6" protocol remained in remission over 1 year, and 18% have been in continuous remission for 2 to over 4 years. Even after discontinuing treatment, some patients with AML stay in remission for long periods, and it is possible that some of them may have been cured. If this proves to be true, it becomes of great importance to determine what is different about the patients who do exceptionally well as compared to the majority who continue to die within a year. However, no consistent nor distinctive favorable prognostic features have yet been identified.

Monoblastic transformation developed in a 26-year-old white man with chronic myelogenous leukemia and was manifested by acute, fulminant hepatic failure due to massive blastic infiltration of the liver. The hepatic failure responded dramatically to radiation therapy. The monocytic origin of the blasts was confirmed by means of light and electron microscopic examination and cytochemical studies. Cytogenetic studies of the leukemic blasts revealed a Philadelphia-chromosome-positive karyotype and a clonal evolution of chromosome changes resulting in multiple karyotypes.

To see whether urine enzyme activities could be used as an index in evaluating the disease status of leukemia patients, we examined the activities of four enzymes: arylsulfatases A(AS-A) and B(AS-B), alkaline phosphatase (AP), and lactate dehydrogenase (LDH). AP and LDH showed no consistent patterns. The activities of AS-A and AS-B correlated well with the patient's clinical status, increasing during progression of disease and decreasing toward normal activities during responses to therapy, as judged from bone marrow cellularity and differential. Among 23 untreated patients with a histologic diagnosis of acute leukemia we found increased activities of the urine enzymes in these proportions: AS-A in 23 patients (100%), AS-B in 22 (95.7%), AP in 7 (30.4%), and LDH in 10 (43.5%). Five patients in remission from acute leukemia had normal activities for all four enzymes. In one patient in remission for more than one year, a rise in urinary arylsulfatase activity preceded observable bone marrow relapse by 4 months. Unlike that of serum of urine lysozyme and serum copper, the determination of urine arylsulfatase activities appears to be a consistent, useful indicator of response to antileukemic therapy. In contrast to the determination of polyamines, the quantitation of arylsulfatase activity is achieved with greater ease and with instrumentation available in most clinical laboratories.

The relation between the quantified French-American-British cooperative study (FAB) classification and presenting features was studied in 123 adult patients (greater than or equal to 15 years) with acute myeloid leukemia. Myeloblastic leukemia with maturation (M2) patients with a high maturation index (M2a) were older, compared to the other myeloblastic subgroups, while promyelocytic leukemia (M3) patients were younger than those with M2 or M2a. Differences between various leukemia types were found in the occurrence of a preceding myelodysplastic syndrome, leukocyte count, and platelet count. In both monoblastic leukemia (M5) and myeloblastic leukemia (M1-3) a smaller degree of maturation seemed to be related to a larger tumor mass. The effect of chemotherapy was analyzed in a group of 64 patients. Comparison between immature (M1) and more mature (M2) myeloblastic leukemia suggested a longer duration of first complete remission and a longer survival in M2. The findings of this study may imply that the degree of maturation determines tumor mass and the success of chemotherapy.

In order to determine whether the use of a sequence of chemotherapeutic regimens plus BCG could produce longer durations of remission in adult acute nonlymphocytic leukemia than maintenance therapy with cytosine arabinoside, 6-thioguanine, plus BCG, a randomized study was performed at Washington University. Upon achieving complete remissions with daunorubicin plus cytosine arabinoside, 14 patients were randomized to receive either: Regimen A--cytosine arabinoside, 6-thioguanine, plus BCG each month; or regimen B--sequential regimens consisting of: 1) azacytidine daily for five days; 2) cyclophosphamide plus cytosine arabinoside daily for four days, prednisone daily for five days, plus vincristine on the first day; 3) prednisone, 6-mercaptopurine, and methotrexate daily for five days plus vincristine on the first day; and 4) cytosine arabinoside, 6-thioguanine, plus BCG. Each of the sequential regimens was given during consecutive months, and the cycle was then repeated starting with the first regimen. Median duration of complete remission was 27 months for 8 patients randomized to receive Regimen A, compared to only seven months for 6 patients receiving Regimen B (P less than 0.05). The median survival time of patients on Regimen B was only 14 months, and has not yet been reached in Regimen A. At 40 months after diagnosis, 75% of patients on Regimen A remain alive (P less than 0.05). Toxicity was equal for the maintenance regimens. Therefore, maintenance therapy with cytosine arabinoside, 6-thioguanine, plus BCG may be superior to the sequence of chemotherapy regimens plus BCG which was employed.