Hematopoietic growth factor (G-CSF or GM-CSF) after salvage chemotherapy in refractory or relapsed adult de novo acute leukemia

Nineteen adults with primary refractory or relapsed acute leukemia (12 ALL and 7 ANLL) were treated with an intensive salvage chemotherapy (intermediate-dose ara-C, intermediate-dose methotrexate, vindesine, cyclophosphamide, mitoxantrone and prednisolone) followed by a hematopoietic growth factor (HGF), either granulocyte colony-stimulating factor (5 μg/kg) or granulocyte-macrophage colony-stimulating factor (10 μg/kg). Both were given from the day after chemotherapy ended and until the neutrophil count rose above 1 × 10⁹/l for three consecutive days. Eleven patients (58%. 95% CI 33% to 82%) achieved complete remission, and 15 courses of salvage therapy were given to these complete responders. In a historical control group that did not receive HGF, 23 out of 38 patients (60%, 95% CI 44% to 77%) achieved complete remission, and 27 courses of therapy were delivered to complete responders. Treatment with a HGF accelerated the recovery of neutrophils to 0.5 × 10⁹/l significantly, shortening it from a mean of 28 to 22 days (p = .0002), with no effect on platelet recovery. There were no differences in the rates of documented and fatal infections, which were relatively high in both groups. In the patients with ANLL, there was no evidence that HGF accelerated leukemic regrowth. We conclude that HGF accelerates neutrophilic recovery following intensive salvage chemotherapy for acute leukemia, although no reduction in documented infections was found. Many factors, including the small patient sample, may have contributed to this latter finding.     

Neonatal neutropenia and thrombocytopenia following maternal hypertension

Objective : To assess the relationship between the subtypes of hypertension in pregnancy and subsequent neonatal haematology.
Methodology : Retrospective review of the haematology of newborns of hypertensive mothers at a tertiary neonatal unit
Results : Over a 2 year period. 249 infants had full blood examinations. Nineteen (7.6%) were neutropenic and 35 (14.1%) thrombocytopenic, including 11 (4.4%) who were both neutropenic and thrombocytopenic. Neutropenia occurred only in infants whose mothers had severe pre-eclampsia and eclampsia or pre-eclampsia with pre-existing hypertension, whereas thrombocytopenia complicated all maternal hypertension subtypes. Two (10%) of the neutropenic infants developed nosocomial infection while seven (20%) of the thrombocytopenic infants bled. Thirteen (68%) of the neutropenic infants compared with 15 (43%) of the thrombocytopenic infants developed their haematological abnormality within 24 h of birth. All but two infants developed the haematological abnormality by the 5th day of life.
Conclusions : Although haematological abnormalities in infants born to hypertensive mothers are uncommon, serious neonatal complications can occur and therefore early haematological screening of these infants is recommended.     

An evaluation of the policy of routine treatment of advanced epithelial ovarian carcinoma by debulking surgery and combined platinum-cyclophosphamide chemotherapy in Singapore

This is an outcome study of a management protocol for patients with FIGO stage III and IV epithelial ovarian cancer treated by debulking surgery and combined platinum and cyclophosphamide chemotherapy. The aim of the study was to determine if the experience of clinical trials could be reproduced in a routine clinical practice in an Asian population. Of the entire group of 62 patients, 50 (80.6%) had the tumor debulked: 26 optimally and 24 suboptimally. Twelve patients had a biopsy of the tumor only. Thirty patients had a histologic grade 3 tumor. Fifty-two (83.9%) patients received the combined platinum-cyclophosphamide chemotherapy. Of these, 49 were assessable for response, and the overall response rate was 49.0%, with 20.4% complete and 28.6% partial response. The overall 5-year survival was 6.8% and the disease-free survival was 4.7% for the entire cohort. The platinum-cyclophosphamide chemotherapy responders showed a significantly better 5-year survival rate of 29.5%, compared to no survival beyond 42 months among the non-responders. Apart from nausea, vomiting and alopecia, the other toxicities of chemotherapy were mild and mostly hematological. These results showed that the management protocol of debulking surgery and combined platinum-cyclophosphamide chemotherapy could be applied routinely in more than 80% of patients with advanced epithelial ovarian cancer. Although the chemotherapy response rate was lower in this clinical study compared to other clinical trials, the overall benefit on survival appeared to be similar. It is concluded that advanced epithelial ovarian carcinoma should continue to be treated actively with debulking surgery followed by combined platinum-cyclophosphamide chemotherapy.     

Fever and neutropenia in children with cancer: diagnostic parameters at presentation

We evaluated 91 episodes of fever in 46 profoundly neutropenic children with cancer, in a search for any symptom, sign or laboratory test that would serve to identify patients with septicemia and differentiate them from those in no immediate need of prompt antimicrobial therapy. Seventeen episodes (19%) were bacteremias, 59 (64%) were suspected septic infections, 9 (10%) were focal bacterial infections and 6 (7%) proved not to be bacterial infections. We were unable to detect any parameter, either on admission or after two days of antimicrobial therapy (except for blood culture findings), that would be helpful in differentiating bacteremia from an episode not of bacterial origin. We focused on serum levels of C reactive protein and found them unreliable on an individual level. Prompt institution of antimicrobial therapy at the occurrence of fever results in low mortality, but does not allow assignment of cases to different categories.     

Infections in acute leukemia: an analysis of 240 febrile episodes

Infections are the major cause of morbidity and mortality in acute leukemia patients. Case records of 91 consecutive patients (AML-48, ALL-40, RAEB-t/AML-3) treated between January 1997 and July 1999 were studied to determine the type, frequency and severity of infections. Patients' median age was 36 y (range 6–66) and male to female ratio was 2.5:1. A total of 240 febrile episodes were recorded; of them, 162 were associated with neutropenia (absolute neutrophil count, ANC<500/mm³) and 78 were without neutropenia. Among the neutropenic episodes, an infectious etiology could be documented in 52%; the remainder (485) were defined as isolated febrile episodes. Chest was the most common site of infection (35.7%) followed by skin, soft tissue (13%), GIT (7%) and genitourinary tract (6%) infections in order of decreasing frequency. Microbiologically, gram positive organisms (staphylococcus aureus, coagulase negativestaphylococcus, streptococcus, enterococcus) were the most common isolates (52.8%) followed by gram negative organisms (E. coli, klebsiella, pseudomonas) in 42.8% of isolates. Two patients had pulmonary tuberculosis and three patients had fungal infections (candida—2,aspergillus—1). Among non-neutropenic patients, infection could be documented in 36%; the remaining 64% were isolated febrile episodes. Gram negative infections were documented in 50%, gram positive in 305 and fungal infections (candia—4,aspergillus—1,mucormycosis—1) in 20% of them. A combination of third generation cephalosporin and an aminoglycoside were used in 79% of episodes initially; a combination of a newer, penicillin and aminoglycoside (4.6%), double betalactums (4.1%), oral, antibiotics (9.8%) and others were used in the remaining episodes. Fever resolved in 38%, of episodes using the above combinations; in the remainder second line antibiotics (mainly vancomycin) and antifungals (amphotericin-B) were added empirically or depending on culture and sensitivity. In 52.5% of episodes fever resolved after addition of second line antibiotics and antifungals. 11 of 91 patients died of infectious complications in this study. There is a need for improvised diagnostic tests to detect infections early, as well as for new therapies to overcome antimicrobial resistance.     

Steroid responsive cyclical neutropenia

Summary A 19-year old girl with severe cyclical neutropenia associated with life-threatening infection and who responded dramatically to the administration of oral prednisolone is described. During reduction and eventual cessation of steroid therapy normal or near normal neutrophil counts have been maintained, and there has been parallel improvement in clinical well-being. Prior to therapy and at a time of peak blood neutrophil count low numbers of granulocyte-macrophage progenitor cells (CFU-C) were found in the patient's bone marrow, and her lymphocytes co-cultured with normal marrow failed to show the inhibitory effect normally seen with normal lymphocytes.The findings in this patient are compared with those in the two other cases where cyclical neutropenia has been shown to respond to steroids.     

Granulopoiesis in the Neutropenia of Negroes

A number of reports have shown that the peripheral blood neutrophil count in many negroes is considerably lower than in white populations. This neutropenia has been ascribed previously to both genetic and nutritional causes. We have studied bone marrow reserve function and myelopoiesis in 3 negroes with neutropenia, and found these to be normal.