Fifty-seven patients in initial phase of acute promyelocytic leukemia (APL) were treated in the same department with heparin infusion, platelet transfusions, and two related induction regimens both including cytosine arabinoside and daunorubicin. Clinical and biological findings at presentation were studied. The complete remission (CR) rate was 53%. Twenty-seven patients (47%) died during the initial course of the disease, either before day 5 (early death [ED], n = 7) or after day 5 (death in aplasia [DA], n = 20). Most ED was due to intracerebral hemorrhage (6/7), especially when large hemorrhages had been seen on fundus oculi examination. Most DA was due to multivisceral failure (9/20). No correlation was found between initial disseminated intravascular coagulation (DIC) and death. However, the worsening of coagulation parameters during induction therapy, with or without initial DIC, significantly increased the occurrence of renal and respiratory failure which were particularly frequent during the first month. The median duration of survival was short (3.5 months) and the median duration of CR (11 months) was similar to that of other acute myeloid leukemias treated with the same regimens. The possible causes of the high mortality observed during the initial courses of APL and the possible benefit of a more graduate induction chemotherapy are discussed.

Acute promyelocytic leukemia in 57 previously untreated patients.

Acute monoblastic leukemia: a clinical and biologic study of 74 cases.

Between 1972 and 1982, 112 consecutive previously untreated adults (aged 15-69 years, median 26) commenced therapy for acute lymphoblastic leukaemia (ALL) at St Bartholomew's Hospital. The first 63 patients entered into the study received initial treatment which comprised four cycles of adriamycin and vincristine, prednisolone and L-asparaginase with the first cycle (OPAL). In 1978, six cycles were given, with escalating doses of adriamycin and cyclophosphamide from cycle 3 (HEAV'D). Central nervous system (CNS) prophylaxis incorporated intrathecal methotrexate and cytosine arabinoside with cranial irradiation. Maintenance chemotherapy consisted of 6-mercaptopurine, cyclophosphamide and methotrexate for 3 years. Results obtained with the OPAL and HEAV'D regimens were not significantly different. The overall complete remission (CR) rate was 66% (73/111), factors correlating unfavourably with achievement of CR being advanced age (P less than 0.001) and L3 morphology/B-ALL immunophenotype (P less than 0.01). Fifty-three patients have relapsed, the bone marrow being the primary site in 43. Extramedullary relapse alone occurred in 10 (seven CNS, two testicular and one skin). Only three of the 64 patients who had complete CNS prophylaxis subsequently relapsed in the CNS as an isolated site. One patient died in CR, 19 remain in continuous CR between 2.5 and 10.5 years. The median duration of remission of the 73 patients who achieved CR was 18.5 months, factors correlating favourably with duration of CR being low blast cell count at presentation (P less than 0.002) and common ALL immunophenotype (P less than 0.04). Twenty-four patients remain alive, with a median survival of all patients of 18 months. Long-term survival is possible for approximately 20% of adults with ALL treated relatively intensively.

Treatment of acute lymphoblastic leukaemia in adults.

Seven adults with acute promyelocytic leukemia (APL) and disseminated intravascular coagulation were treated for remission induction with daunorubicin hydrochloride and prednisone. In all patients the coagulopathy was managed with continuous-infusion heparin sodium and vigorous transfusion with platelets, cryoprecipitate, and fresh frozen plasma. Five patients survived induction; they all achieved complete remission (CR). Median duration of CR was 27+ months; two patients presently survive in their initial CR at 28 and 48 months. Recognition of APL as a distinct type of acute leukemia and prompt initiation of treatment aimed at rapid cytoreduction and control of the coagulopathy has resulted in a prolonged disease-free survival for the majority of patients. ( Arch Internal Med 138:1677-1680, 1978)

Acute promyelocytic leukemia. Management of the coagulopathy during daunorubicin-prednisone remission induction.

A review of 58 patients with malignancies (age range, 14-73 years), who required surgical consultation for acute abdominal pain in the setting of neutropenia (granulocyte count less than 1000/mm3) after chemotherapy was conducted. Ninety percent had fevers greater than 37.8 degrees C, 30% had diarrhea or melena, and 25% had diminished bowel sounds. Five of the 29 patients (17%) with localized pain had surgical intervention; 3 of 29 patients (10%) with generalized pain underwent operations (2 for x-ray findings). All eight of these surgically treated patients survived to leave the hospital. Eighteen of the 29 patients with generalized pain were believed to have a similar syndrome of diarrhea (occasionally heme positive) and diffuse abdominal tenderness (some with peritoneal signs and distension), which was termed "neutropenic enteropathy." Eleven of these 18 patients had their symptoms resolve with antibiotic therapy, aggressive fluid replacement, and a return of their granulocyte count to normal. The other seven died of pneumonia (two), unknown causes (one), and diffuse enterocolitis throughout the intestinal tract (four documented at autopsy). The overall 30-day mortality rate in this series was 34%. Several factors correlated significantly with mortality: hypotension at the onset of pain (80% mortality), bacteremia (63% mortality), and fungemia (100% mortality). Absolute leukocyte count and absolute platelet count did not correlate with mortality. This study reaffirms that patients with neutropenic enteropathy are best treated conservatively. Patients with surgically correctable disease were identified by specific focal findings on examination or x-ray.

Abdominal pain in neutropenic cancer patients

An analysis of prognostic factors was performed on a series of 92 adult patients with acute non-myeloid leukaemia (ANML). Four factors were shown to be correlated with a poor short-term prognosis: (1) Neuropathy involving a single cranial nerve (numbness of the chin) as a presenting feature. (2) A low percentage blast cell infiltration of bone marrow (less than 55%). (3) Cytological L2 type or L3 type of cells according to FAB classification proposals. (4) Increased age. Two factors were shown to be correlated with a poor long-term prognosis: 1) A high level of circulating blast cells; 2) A high tumour burden, as in childhood ANML. These two long-term prognostic factors were interrelated. In addition, our results suggested that myelofibrosis could be a poor long-term prognosis factor as well.

Acute non myeloid leukaemia in adults. Prognostic factors in 92 patients.

Two hundred bacterial septicemia occurring in neutropenic patients (PMN less than 1,000 microliter) were analyzed. Most of these patients had hematologic malignancies. The underlying disease, the degree of neutropenia the association of septic focus with the bacteremia, the responsive microorganisms and their evolution during hospitalization were studied as prognosis factors. The overall mortality was 32.5 p. 100. The mortality was higher in patients whose granulocyte count was lower than 500 microliter. The occurrence of major septic focus (pulmonary, perineal infection, diarrhea with abdominal distension, ORL, or cutaneous extensive focus) during bacteremia was a highly significant factor of bad prognosis. The mortality of bacteremias with and without major septic focus was respectively 62 p. 100 and 15 p. 100. A study of the distribution of the bacterias was performed in terms of mortality and duration of hospitalization. "Escherichia coli" and gram positive cocci were predominant during the two first days and mortality was then low. After that time, others Gram-negative bacterias appeared, especially "Pseudomonas aeruginosa" and the mortality was increasing until the twentieth day. Therefore, the authors raise the opportunity of antibiotic therapy according to the duration between the beginning of the hospitalization and the occurrence of sepsis in neutropenic patients. The role of the extensive use of a curative antibiotic association using colistine and nalidixic acid between 1974 and 1976 is discussed in the emergence of more gram positive cocci bacteremias between 1976 and 1978 than between 1974 and 1976 in the same intensive care unit.

Bacterial septicemia in neutropenia patients

Emergency treatment of acute promyelocytic leukemia and its hemorrhagic complications. Apropos of 30 cases

Twenty cases of acute monoblastic leukemia are studied according to definite criterias: cytology, cytochemical staining, lysozyme production. The study points out the tumoral characters: hematodermy, gingivitis, central nervous system leukemia and the lack of important bone marrow incompetence. 47 per cent of complete remissions are obtained with daunorubicin, aracytin combination therapy. Other useful chemical agents, and prospects for maintenance therapy are discussed.

Acute monoblastic leukemia. Clinical and therapeutic aspects in 20 cases

Lactic acidosis during acute leukemia

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