Spontaneous remission of acute monocytic leukemia after infection with Clostridium septicum.

Spontaneous remissions of acute myeloid leukemia (AML) have been reported in association with infection. Here, we report a case of spontaneous remission of AML in a 47-year-old Saudi Arabian male patient who presented with a few weeks history of recurrent abdominal pain, vomiting and fever. He was diagnosed with acute monocytic leukemia (AML, FAB M5b) and a perforated bowel. He also had Clostridium septicum bacteremia and thus chemotherapy was deferred. He received supportive therapy and intravenous antibiotics. Six weeks later, he achieved spontaneous and complete remission lasting for about 4 months. The remission and relapse were documented by bone marrow examination. Similarly, previous reports of spontaneous remission of AML were short lived and were followed by relapse and progression.

Isoxsuprine in the treatment of sickle cell painful crises: A double-blind comparative study with narcotic analgesic.

BACKGROUND: Isoxsuprine is a tocolytic agent which improves erythrocyte deformability. It was accidentally found to be effective in the management of sickle cell disease (SCD) painful crises. The experience with the drug in the treatment of sickle cell disease is limited. This double-blind randomized comparative study was undertaken to test its efficacy and safety in the treatment of SCD painful crises. PATIENTS AND METHODS: Forty-three SCD patients (33 males and 10 females) with 44 episodes of pain were included in the study (i.e., one patient was included twice). Only those with painful crises requiring hospital admission were included. Patients were randomized to receive either isoxsuprine 5-10 mg, or meperidine 50100 mg intramuscularly, according to body weight, every four hours. A random selection of 23 patients received isoxsuprine, and 21 received meperidine. Pain score, duration of crisis, hospital stay, and side effects were monitored. RESULTS: No significant difference was found in any parameter except for pain score at 30 and 60 minutes. CONCLUSION: We conclude that isoxsuprine appears to be effective in the treatment of sickle cell painful crises. Confirmation of its efficacy in studies involving a larger number of patients is warranted.

Fetal hemoglobin in acute and chronic states of erythroid expansion.

Physiologic principles underlying the differences in fetal hemoglobin (HbF) induction between acute and chronic states of erythroid expansion are poorly understood. Whereas abrupt erythroid expansion is characterized by a high proportion of reticulocytes coexpressing adult and fetal globin (F reticulocytes), HbF levels wane with chronic erythropoietic stimulation. To investigate this phenomenon, we used various schedules of erythropoietin (epo) administration in primates. Acute intravenous epo administration promoted a 2- to 10-fold preferential induction of F reticulocytes compared with total reticulocytes. Total reticulocyte and F reticulocyte production were significantly correlated (correlation coefficient .41 to .74). With chronic epo administration, preferential F reticulocyte production was lost, and there was no correlation between reticulocyte and F reticulocyte production (correlation coefficient -.03). The mean percentage of F reticulocytes did not change between acute and chronic schedules of epo administration. The subcutaneous route of high-dose (3,000 U/kg) epo administration was as effective as intravenous administration in the induction of HbF. Reticulocyte and F reticulocyte responses to increasing epo doses were found to be saturable. These results suggest that the kinetics rather than absolute levels of reticulocyte and F reticulocyte response form the basis for preferential F reticulocyte induction with acute erythropoietic stimulation, and they support the hypothesis that F reticulocytes arise from a relatively rapid pathway of erythroid maturation.

Antiemetic efficacy of cimetidine randomized, double-blind, crossover study with dexamethasone in cancer patients receiving emetogenic chemotherapy.

In a randomized, double-blind, crossover study the antiemetic effect of cimetidine was compared with that of dexamethasone in cancer patients receiving emetogenic chemotherapy. Thirty-two patients were evaluable and all were chemotherapy-naive. Eight patients (25%) received high doses of cisplatin, 17 (53%) had cyclophosphamide in combination treatment, 2 (6%) received adriamycin, and 1 another chemotherapy of less emetogenic potential. Complete protection (CR) rates of 59.4% and 62.5% were achieved with cimetidine and dexamethasone, respectively. In addition, three (9.4%) and 1 (3%) patients attained partial protection with cimetidine and dexamethasone, respectively. No significant difference was noted between the two antiemetic therapies (p = 0.07). Although CR has not been achieved in any of those patients who received cisplatin, a comparable antiemetic effect was attained. Both antiemetic regimens were well tolerated with minimal side effects. We conclude that the antiemetic potential of cimetidine and its safety deserve further investigation in a larger study, perhaps in combination with other antiemetic agents.

Induction of fetal hemoglobin by cell-cycle-specific drugs and recombinant erythropoietin.

During the last several years, studies in humans and experimental animals have identified several compounds that induce fetal hemoglobin in the adult. These include: cell-cycle-specific drugs, other cytotoxic drugs, butyric acid analogs, and erythropoietin. Several of these compounds induce fetal hemoglobin indirectly by triggering kinetics of rapid erythroid regeneration. High doses of erythropoietin increase the frequency of erythroid progenitors programmed to hemoglobin F. This results in transient increases of hemoglobin F-containing cells (F cells) in the peripheral blood. Erythropoietin and hydroxyurea increase F cells in a cooperative fashion. Although high doses of erythropoietin can induce F cell production in humans, the practical relevance of such observations is unclear

Effects of interleukin-3 and erythropoietin on in vivo erythropoiesis and F-cell formation in primates.

To test the in vivo cooperativity between interleukin-3 (IL-3) and erythropoietin (Epo) in stimulating erythropoiesis and hemoglobin F (HbF) production in primates, we administered recombinant human IL-3 and recombinant human Epo to baboons and macaques. The effect of these treatments was assessed by serial bone marrow cultures and by measuring HbF production in the progeny of bone marrow progenitors and in peripheral-blood reticulocytes. Administration of IL-3 alone to hematologically normal or anemic baboons produced an early increase in erythroid colony-forming units (CFUe) and erythroid clusters (e-clusters) with an increase in reticulocyte counts and a late increment in the relative frequency of erythroid burst-forming units (BFUe). In parallel to the increase in peripheral-blood reticulocytes, IL-3 increased the frequency of F reticulocytes in the normal and anemic animals. When administration of IL-3 was followed by administration of Epo, expansion in all classes of erythroid progenitors and increase in reticulocytes occurred, beyond the levels observed when the animals were treated with Epo alone. The combination of IL-3 and Epo, however, did not increase consistently the rate of F reticulocytes beyond the level induced by Epo alone. These results suggest that IL-3 enhances the effect of Epo on erythropoiesis, but the combination of the two growth factors does not lead to a preferential and significant enhancement of HbF production.

Fetal hemoglobin synthesis in vivo: direct evidence for control at the level of erythroid progenitors.

To test directly whether the control of fetal hemoglobin (HbF) in the adult takes place at the level of erythroid progenitors or at the level of erythroblasts, we treated animals with high doses of erythropoietin and examined the effects of this manipulation on the globin gene programs of erythroid progenitors. We found that administration of erythropoietin produced a rapid expansion of all classes of erythroid progenitors. Almost all the expansion of colony-forming units-erythroid and 46-56% of erythroid clusters was due to the increase of HbF-programmed erythroid progenitors. The expansion of HbF-programmed erythroid progenitors was followed, 2-3 days later, by a wave of reticulocytes containing HbF in the peripheral blood. These results provide direct in vivo evidence that fetal-globin expression in the adult is controlled at the level of erythroid progenitors.

Cooperative enhancement of F-cell formation in baboons treated with erythropoietin and hydroxyurea.

Chronically anemic baboons on a continuous hydroxyurea regimen were treated with pulsed doses of recombinant human erythropoietin (rHuEpo) to test whether the combination of these two compounds, which individually induce F-cell production, can enhance further F-cell output. A low-F-cell-responding animal under chronic hydroxyurea treatment was given three separate pulses of Epo and responded with F-reticulocyte increments that were similar to the sum increments caused by either hydroxyurea alone or rHuEpo alone. The same results were obtained in a high-F-responding animal similarly treated. These findings suggest that rHuEpo and hydroxyurea can increase F cell numbers in an additive fashion. It is speculated that both compounds act through perturbation of erythroid differentiation kinetics.

Stimulation of fetal hemoglobin synthesis by erythropoietin in baboons.

Stimulating the production of fetal hemoglobin may benefit patients with sickle cell anemia by inhibiting sickling. We gave pulsed treatments with high doses of recombinant human erythropoietin to baboons in order to test the hypothesis that the resultant rapid erythroid regeneration would stimulate F cells--i.e., cells that contain fetal hemoglobin. In normal animals, this treatment caused sharp increments in F-reticulocyte levels, which rose from 1 to 2 percent before treatment to 40 to 50 percent afterward. In two animals with chronic anemia and high levels of endogenous erythropoietin, recombinant human erythropoietin induced further increments in F-reticulocyte levels, which rose in one animal from 6 to 8 percent before treatment to 23 percent after treatment, and in the other from 20 percent before to 50 percent afterward. The time course of F-reticulocyte stimulation suggested that these cells were the products of mobilized early erythroid progenitors. These results raise the possibility that pulses of erythropoietin could be used to stimulate F-cell formation in patients with sickle cell disease.