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Aplastic anaemia is both frequent and difficult to manage in patients with dyskeratosis congenita (DC). We recently treated a 23-year-old male for a year with granulocyte colony-stimulating factor (G-CSF) and erythropoietin (Ep), with an excellent neutrophil response, and a transient effect on haemoglobin levels. G-CSF alone or combined with other cytokines may provide at least a partial effect in pancytopenic patients with DC.

Background and Objective: Hypoplastic myelodysplastic syndromes (MDS) are being reported with increasing frequency. Aplastic anemia (AA) needs to be differentiated from hypoplastic MDS particularly primary hypoplastic refractory anemia (PHRA) because of the impact on management and prognosis. This distinction may be morphologically difficult even with careful marrow examination which may provide insufficient material due to extreme hypocellularity. The value of peripheral blood (PB) parameters in making the distinction between AA and PHRA is not well studied. In this work, we attempt to examine peripheral blood findings as an additional tool for differentiating PHRA from acquired idiopathic AA., Methods: PB findings in ten cases of PHRA, which are selected based on the following: less than 30% cellularity, multilineage dysplasia and/or clonal cytogenetic abnormality, are compared to ten cases of classic AA. The PB is examined for automated parameters, differential white cell count, morphologic changes in red cells, white cells, platelets, and the presence of circulating blasts, megakaryocytic fragments and micromegakaryocytes., Results: AA patients tend to have lower platelet and monocytic counts and higher lymphocytic percentages. The following morphologic findings are seen only in PHRA but not in AA: hypochromic red cells, left shift, circulating blasts, hypersegmentation with long filaments, hypogranular, ring, and pelgeroid neutrophils, Dohle bodies, circulating micromegakaryocytes and megakaryocytic fragments., Interpretation and Conclusions: We conclude that careful examination of peripheral blood may provide sufficient information to allow for the distinction between PHRA and AA early in the course of the disease. Similarly, patients with classic AA who subsequently develop unusual blood findings during routine follow up should be suspected of having a clonal evolution which needs to be confirmed by marrow examination and cytogenetic analysis.

Five patients with the classical clinical syndrome associated with a deletion of the long arm of chromosome 5, i.e., anemia, macrocytosis, and thrombocytosis, or a normal platelet count, were treated successfully with subcutaneous low-dose cytosine arabinoside (LDARA-C). Prior therapy with other drugs had failed in four of the five patients. A total of nine complete and one partial hematologic responses were induced in five patients. Duration of the first hematologic response ranged from 3 to 30+ months. Two patients (cases 3 and 4) continue in their first hematologic response at 29 and 30 months. Upon relapse, up to three responses could be reinduced in two patients. Duration of the subsequent hematologic responses in case 1 was 16, 8, and 10 months and case 2 achieved two responses of 15 and 18+ months duration. LDARA-C therapy was associated with mild to severe neutropenia and moderate to severe thrombocytopenia. Thus, subcutaneous LDARA-C is highly effective in the treatment of patients with myelodysplasia associated with deletion of the long-arm of chromosome 5 (5q-).

To study the characteristics of the microenvironment of human bone marrow, fibroblasts derived from normal and aplastic anemia bone marrow aspirates or core biopsies were grown in culture. Normal bone marrow fibroblasts had a slow logarithmic phase of growth (8 days) with doubling times of 2 to 3 days. Aplastic anemia bone marrow fibroblasts had a rapid logarithmic phase of growth (5 to 6 days) and doubling times of 1 day. Dexamethasone (1 X 10(-8) M) stimulated the growth of normal fibroblasts. Growth of fibroblasts derived from aplastic anemia marrows was, however, inhibited by dexamethasone. Specific binding sites for the hormone were present in the normal fibroblasts (Bmax: 460-770 fmole/mg protein) whereas in the aplastic anemia fibroblasts the amount was very low (Bmax 27-215 fmole/mg protein). These observations suggest that in aplastic anemia, the bone marrow fibroblast, a cell constituent of the marrow microenvironment, has the capacity to develop and grow in vitro. However, this cell is different from normal bone marrow fibroblasts in its growth characteristics and response to dexamethasone.

A method is described for the separation of early and intermediate myeloid cells from human bone marrow aspirates. This easily performed procedure is based on preferential binding of lymphoid and late myeloid cells to DEAE-Cellulose-Sephadex G-25 columns.

New automated blood cell analyzers provide an index of red cell volume distribution width (RDW) or heterogeneity and a histogram display of red cell volume distribution. We have developed a classification of red cell disorders, based on mean corpuscular volume (MCV) or red cell size, heterogeneity, and histograms, to guide diagnosis from the peripheral blood analysis. The distinction of iron deficiency anemia from heterozygous thalassemia or the anemia of chronic disease and the detection of early iron and folate deficiency is improved. Red cell volume distribution histograms identify red cell fragmentation or agglutination, dimorphic populations, and artifactual counting of lymphocytes as red cells. We recommend the use of these new variables in the initial classification of anemia by the practicing physician.

Human bone marrow fibroblasts (BMF) were grown in vitro from normal (N) subjects and patients with aplastic anemia (AA). Growth studies in vitro revealed that both the N-BMF and AA-BMF had a logarithmic growth phase of eight days. Population doubling time for six of the 12 N-BMF and seven of the 12 AA-BMF was greater than 50 h. Five of the 12 AA-BMF studied in contrast to only two of the 12 N-BMF had a population doubling time of less than 50 h. The remaining four N-BMF had a population doubling time of greater than 100 h. During a similar duration in the logarithmic phase of growth, the AA-BMF underwent an average of 2.499 population doublings in comparison to 1.586 doublings by N-BMF (P = less than 0.01). The AA-BMF grew in multiple layers compared with the N-BMF, which usually grew as a monolayer. At the end of the logarithmic phase of growth, the AA-BMF also had a significantly higher number of cells per dish than the N-BMF (P = 0.02 on analysis of variance and covariance). These data suggest that a subgroup of AA-BMF grows faster than N-BMF and that the AA-BMF lack cell-to-cell inhibition. Testosterone, 3 alpha-etiocholanolone, and dexamethasone at 1 X 10(-8)M concentration, a physiological concentration, stimulated the growth of N-BMF as evidenced by increase in cell numbers and radioactive thymidine (3H-TdR) uptake. While dexamethasone had a stimulating effect on growth of N-BMF, it suppressed the growth of AA-BMF. Specific binding of radioactive dexamethasone (3H-dexa) was determined both for the N-BMF and AA-BMF. Specific binding sites for dexamethasone (Bmax) present on the N-BMF ranged from 460 to 770 fmol/mg protein). Bmax for AA-BMF was low (27-215 fmol/mg protein). In addition, the dissociation constant (Kd) was ten times lower for AA-BMF (1.0 X 10(-7) M) than for N-BMF (1.1 X 10(-8) M). The observations on the growth studies, the paradoxical response to dexamethasone, and the difference in the number of binding sites for dexamethasone indicate that the marrow fibroblasts from patients with aplastic anemia are abnormal.

An increasing number of kindreds with thrombocytopenia have been described in the past decade as platelet counts have been done regularly. These patients are delineated from ITP, recognizing that some patients with hereditary thrombocytopenia may benefit from splenectomy. Until more information on platelet biochemical information is available, these disorders have been categorized by platelet size, now quantifiable as mean platelet volume (MPV). The availability of rapid and quantitative measurement of platelet count and MPV allow a better understanding of megakaryocyte proliferation and platelet production. The evolving changes of MPV during treatment and recovery from chemotherapy will now allow a forecast of marrow hypoplasia, since the platelet count and increase in MPV follow the increase in megakaryocyte ploidy to herald marrow regeneration. It is anticipated that the careful plotting of the MPV relationship to the platelet count will allow the physician to evaluate marrow function indirectly, in many cases replacing repeated bone marrow studies.

Aliquots (0.1 mL) of whole-blood pools prepared to contain various concentrations of phenylalanine were applied to filter-paper collection cards, dried, and stored in sealed bags. We measured the phenylalanine content of the dried blood spots by bioassay, fluorometry, and "high-performance" liquid chromatography, and found that the concentrations remained constant for two years when samples were kept at -20 degrees C or lower. Intra- and interlaboratory studies showed that results for phenylalanine were greater for laboratories using bioassay procedures than for those using fluorometric procedures. Further, CVs (both among- and within-laboratory) obtained with fluorometric procedures were nearly half as great as the CVs obtained by laboratories using bioassay techniques.

The bleeding complications of some forms of thrombocytopenia are difficult to control. Many patients become refractory to platelet transfusions even when HLA-matched. We have successfully used aminocaproic acid to control bleeding in 13 patients with amegakaryocytic thrombocytopenia. Four patients receiving long-term therapy with this drug had striking reductions in the number of platelet transfusions required for capillary bleeding. No adverse effects have been noted save for orthostatic hypotension, which is ameliorated by a reduction in dosage. Quantitative platelet function changes have been impossible to demonstrate, but no changes were noted in four patients with normal platelet counts who were receiving high-dose aminocaproic acid for treatment of subarachnoid hemorrhage. Aminocaproic acid has proved to be a valuable agent in the management of patients with amegakaryocytic thrombocytopenia, especially in decreasing the need for platelet transfusions.

The effect of marrow stromal cells (MSC) on the clonal growth of a human malignant T-lymphoblast (MTL) cell line was investigated in a bilayer culture system. The MSC consistently stimulated clonal growth of MTL, and no stimulatory humoral factor was present in the medium conditioned by the MSC. These observations and other reports suggest that marrow stromal cells may provide a microenvironment in vivo that is not only conducive to the growth of malignant lymphoblasts, but may actually enhance proliferation of malignant T-lymphoblasts in the bone marrow.

The current published reports have indicated that the young patient with aplastic anaemia who has a compatible marrow donor can obtain a successful marrow graft, especially if sex matched and with a past record of little or no transfusion therapy. Despite these encouraging results, only a small number of patients will have such donors available. Immunosuppressive therapy has been considered as an alternative, but this treatment has high risk in older patients. Past studies with androgen therapy have reported a response rate at one year similar to the current recovery rates with bone marrow transplantation. However, contemporary reports have indicated a marked decrease in the recovery rate following androgens, and some of these comparisons may be related to differences in supportive transfusion therapy. In part, the decreased rates may be related to an inadequate evaluation of residual marrow function in the aplastic patient. Patients to be treated with androgens always should have a physiological evaluation of residual erythropoietic committed bone marrow cells. In the absence of such an erythropoietic nidus, one may anticipate a poor response to any steroid therapy. Supportive blood component transfusions should be provided, especially in the initial three months of androgen treatment. In past studies the majority of patients have received only oral androgens, predominantly oxymetholone. Other androgens may be more effective in a particular patient, and there is an urgent need to develop procedures that define stem cell receptors for specific testosterone preparations. Current investigations have indicated that the 5 beta steroid metabolites of testosterone are haematopoietic without the complication of virilization. It is anticipated that a variety of these metabolites can be prepared for evaluation in the patient with aplasia. While there is continuing evaluation of the immune responses and suppressive therapies the clinician should continue to treat the aplastic patient with vigorous supportive transfusion therapy and different androgens for comparative evaluation.

Twenty-nine patients with aplastic anemia and 11 patients with myelofibrosis were evaluated with indium-111 chloride bone-marrow imaging, ferrokinetics, and bone-marrow core biopsies. There was good correlation between the erythrocyte cellularity of the marrow and the In-111 bone-marrow scan grades in most patients. In some, the overall scan grade tended to underestimate the erythroid elements because the core biopsy had been taken from the area of the greatest radionuclide concentration on the scan. In patients with aplastic anemia, there was good correlation between the plasma iron clearance t1/2 and the scan grade. Less agreement was found in the comparison between the Fe-59 sacral and organ counts and the red-cell iron utilization. In patients with myelofibrosis, there was poor correlation between the surface counts over the sacrum and the red-cell iron utilization. Plasma iron clearances were abnormally short and were unrelated to the transferrin saturation levels. Eighteen patients were studied several times to evaluate their responses to steroid therapy. In all, there was good correlation between the bone-marrow imaging, the erythrocyte cellularity, ferrokinetics, and the patient's response to therapy. Indium-111 bone-marrow imaging is useful both in evaluating marrow erythroid activity and in following the response to therapy in patients with these diseases.

Patients with bone marrow failure may have a hematopoietic response to an androgen preparation after they have no response from the use of a previous testosterone preparation. The failure to try a variety of hormone preparations may lead to improper conclusions as to a potential marrow proliferation for a clinical response. In some instances the use of a 5beta steroid metabolite may initiate stem cell proliferation in patients previously refractory to testosterone or nontestosterone esters. These obsevations suggest that some patients refractory to testosterone may be unable to form adequate 5beta metabolities by alterations in 5alpha reductase or enhanced metabolic transformation of the androgen. All patients should be evaluated with several androgen esters before concluding that their marrow cannot achieve a hematopoietic response.

In an attempt ot determine the indications for platelet transfusion in thrombocytopenic patients, we randomized 56 children with acute leukemia to one of two regimens of platelet transfusion. The prophylactic group received platelets when the platelet count fell below 20,000 per mm3 irrespective of clinical events. The therapeutic group was transfused only when significant bleeding occurred and not for thrombocytopenia alone. The time to first bleeding episode was significantly longer and the number of bleeding episodes were significantly reduced in the prophylactic group. The survival curves of the two groups could not be distinguished from each other. Prior to the last month of life, the total number of days on which bleeding was present was significantly reduced by prophylactic therapy. However, in the terminal phase (last month of life), the duration of bleeding episodes was significantly longer in the prophylactic group. This may have been due to a higher incidence of immunologic refractoriness to platelet transfusion. Because of this terminal bleeding, comparison of the two groups for total number of days on which bleeding was present did not show a significant difference over the entire study period.

Classification of platelet disorders has been based on the platelet count. Addition of a second variable, mean platelet volume (MPV), to the routine blood count allows classification of patients into 9 categories: high, low, or normal MPV, and high, low or normal platelet count. We studied 1,244 adult inpatients. 1,134 had both platelet values normal. 11 patients had high MPV and low platelet count: all had hyperdestructive causes. 15 patients had high MPV and normal platelet count: 12 had heterozygous thalassemia, and three had iron deficiency. Seven patients had high MPV and high platelet count: causes included myeloproliferative disorders, inflammation, iron deficiency, and splenectomy, 25 patients had high platelet counts and normal MPV: the causes were inflammation, infection, sickle cell anemia, iron deficiency, or chronic myelogenous leukemia. 52 patients had an MPV that was inappropriately low for the platelet count (high, normal, or low). All had sepsis, splenomegaly, aplastic anemia, chronic renal failure, or a disease being treated with myelosuppressive drugs. High MPV thus appears correlated with myeloproliferative disease or thalassemia; and low MPV, with cytotoxic drugs or marrow hypoplasia. Addition of MPV to the platelet count allows subtler disorders to be detected (when the platelet count is normal), and allows distinction of the cause of thrombocytopenia.

In 32 patients with myeloproliferative disorders (MPD), correlations were made among clinical observations of hemorrhagic tendency, template Ivy bleeding time, and platelet aggregation studies. Bleeding time was commonly prolonged, particularly in myelofibrosis. In two cases, this prolongation appeared to reflect a defect in platelet function, which resulted in clinical bleeding. Prolongation of bleeding time did not correlate with degree of thrombocytosis. Two patients with thrombocytosis had serious clinical bleeding at a time when bleeding time was normal. Of the patients, 35% had abnormal findings from aggregation studies, but there was no correlation between aggregation studies and prolongation of bleeding time or clinical hemorrhage. We conclude that bleeding in MPD arises either from a defect in platelet function, which is reflected in a prolonged bleeding time, or from thrombocytosis.

Sixteen adults with chronic acquired aplastic anemia had abnormally large RBCs and abnormally small platelets before chemotherapy. During their therapy, transfusion initially obscured these macrocytic RBCs. In the eight who had erythropoietic recovery, endogenous RBCs again were macrocytic, and platelets remained small whether or not the platelet count increased. The percentage of cells containing hemoglobin F changed in only one of the eight subjects. In contrast, the eight who did not have erythropoietic recovery had no reappearance of macrocytes. Of 19 other previously treated patients whose hemoglobin level had recovered to normal for seven to 196 months, 16 had increased mean corpuscular volume (101 to 133 femtoliters) and abnormally small platelets. We conclude that in aplastic anemia the appearance of macrocytes reliably and easily predicts RBC recovery. Furthermore, even in treated, apparently recovered subjects, an abnormality of blood cell size remains.

Studies were undertaken to determine whether EDTA was a satisfactory anticoagulant for tissue specimens for cytogenetic analysis and to investigate a modification of a currently used culture technique for obtaining metaphases. The latter involved to prolonged exposure to very low-dose colcemid and was successful in qualitative or quantitative enhancement, or both, of the temperature yield over that obtained from direct harvest in 53% of the patients studied. EDTA is a suitable anticoagulant for cytogenetic studies of specimens from either direct harvest or short-term culture if the specimen is either processed within 24 hr after collection or diluted 1:1 with Eagles minimal essential media, supplemented with fetal bovine serum and refrigerated until processed. Success has been obtained with specimens stored up to 144 hr.

In normal persons, the mean platelet volume varies inversely but nonlinearly with the platelet count. Those with immune platelet destruction have a mean platelet volume that conforms to normal values. Nine patients with thrombocytopenia due to post-trauma sepsis without disseminated intravascular coagulation had a lower than normal mean platelet volume as the platelet count fell. In six patients who recovered, the mean platelet volume increased to the normal value before the platelet count began to rise. In contrast, three patients who did not recover from sepsis had no change from the low mean platelet volume and thrombocytopenia. Since mean platelet volume can now be part of the routine blood count, it is a useful variable to assay the degree of bone marrow suppression in the patient with thrombocytopenia and can be used as a predictor of recovery from thrombocytopenia.

Dyskeratosis congenita (DC) is a rare familial hematologic disorder that has various modes of inheritance. We have studied 2 siblings with DC. 1 sibling had thrombocytopenia, which responded to therapy with nandrolone decanoate and oxymetholone. Platelets were abnormally small, which indicates that a qualitatively abnormal megakaryocytopoiesis is a feature of DC. Myeloid and erythroid progenitors in specimens of the blood and bone marrow from both siblings were either absent or greatly reduced in numbers. The qualitatively abnormal megakaryocytopoiesis, and the quantitative abnormality of hematopoietic progenitor cells committed to myelopoiesis and erythropoiesis, indicates involvement of the pluripotent stem cell in DC. Cytogenetic studies of the bone marrow and peripheral blood lymphocytes from these patients showed normal karyotypes, a normal sister chromatid exchange frequency, and a rapid proliferation of peripheral T lymphocytes, a feature of the disorder that has not been reported previously.

A cell fraction enriched in immature granulocytes was obtained after fractionation of human bone marrow by a three-step procedure. This fraction sediments at an average density of 1.073 and has a high content of myelocytes and metamyelocytes. It showed the highest specific uptake of etiocholanolone when compared to other bone marrow cell fractions. Autoradiographic studies demonstrated a higher number of silver grains over myelocytes and metamyelocytes than in other cell types. These results suggest the presence in human bone marrow of a target cell for etiocholanolone, located in the late mitotic or postmitotic pool or granulocytes.

Long-term bone marrow cultures (LTMC) were initiated with marrow from five normal subjects and eight patients with aplastic anemia (AA). Near confluent to confluent adherent layers developed in all cultures from normal subjects and AA patients. When present, the 'cobblestone' areas in LTMC from AA subjects were smaller than those observed in the LTMC from normal subjects. The decline in total and viable cell numbers in the LTMC was similar for both normal subjects and AA patients. Granulocyte-macrophage colony-forming units (CFU-gm) were present in nonadherent cells (NAC) from normal LTMC for a mean of 5.2 weeks. CFU-gm were present in the NAC of only two of the eight AA cultures for one week. The absent or small 'cobblestone' areas and the absence of CFU-gm production in AA-LTMC suggest a decrease in the reproductive potential of adherent hematopoietic stem cells, which may be the result of either an abnormal hematopoietic stem cell or an abnormal stromal microenvironment or both.

Mononuclear cells from the peripheral blood of a patient with megakaryoblastic transformation of Philadelphia chromosome-positive chronic myelogenous leukemia were cultured. Morphological and cytochemical studies and cell ploidy determinations were done daily for 4 days. PAS staining of the cells increased progressively during culture. Ultrastructural study of circulating and cultured cells revealed demarcation membranes and alpha granules indicating the cells were micromegakaryocytes. Deoxyribonucleic acid synthesis, determined by 3H-thymidine uptake, peaked at 72 hours. The DNA content of cultured cells was diploid at all times. All 15 metaphases analyzed at 72 hours were Ph1-positive. Malignant (Ph1-positive) megakaryoblasts and micromegakaryocytes grown successfully were capable of partial cytoplasmic maturation as demonstrated by glycogen deposition and increase in subcellular organelles, while endoreduplication was impaired. Malignant megakaryoblasts and micromegakaryocytes can be grown successfully in short term liquid culture and have more complete maturation in vitro than observed in vivo.

Eight patients with anemia and chronic renal disease being maintained by chronic hemodialysis were evaluated with In-111 chloride bone marrow imaging and bone marrow core biopsies. There was no correlation between the erythrocyte cellularity of the marrow and the indium bone marrow scan grade in any patient. Bone marrow imaging can not be used as an indicator of the presence of erythroid marrow in these patients.

In erythroblasts of varying maturational stages, cytoplasm stained bright yellow with bromochlorophenol blue. Since this staining reaction appeared to be distinctive among various cytological types of marrow cells, it may constitute a rapid method for visualization of cells of erythroid origin.

The responses of 23 patients with agnogenic myeloid metaplasia (AMM) to androgen therapy were studied. Various clinical and laboratory parameters were analyzed for their value in determining response to therapy and length of survival. Fifty-seven percent of patients responded, as determined by a sustained increase in hematocrit within three months of therapy which thus eliminated the need for transfusions. Chromosome study of the abnormal hemic population was the best predictor of response: 92% of patients with normal chromosomes responded, while 78% of patients with chromosomal abnormalities did not. Responders had a mean survival time of five and a half years from the time of diagnosis as compared with two years for the nonresponders. The degree of thrombocytopenia, suppression of the ferrokinetic, and lack of activity in axial skeleton on bone marrow scans indicated severely compromised hemopoiesis in the nonresponders. The results suggest that in some patients with AMM, more extensive cytogenetic alterations in the abnormal hematopoietic cells result in an inability to respond to androgen therapy and that the chromosome study is the test most accurate for predicting the outcome of therapy.

To study the process of red cell membrane protein synthesis we have followed the time course of [3-H]leucine appearance in total protein and individual peptides of the erythrocyte membrane following injection of the amino acid into phenylhydrazine-anemic rabbits. Multiple peripheral blood samples were taken from single animals over a 5-week period. Erythrocyte membrane proteins were separated by polyacrylamide gel electrophoresis in sodium dodecylsulfate and dithiothreitol; incorporation of radioactivity was determined by gel slicing and liquid scintillation spectrometry. Appearance of [3-H]leucine in circulating erythrocytes reached a peak at 1-3 days, with a steady decline thereafter. The radioactive amino acid appeared first in the lowest molecular weight peptides and last in the largest peptides; at the earliest time point (8 h), little radioactivity was observed in any of the four largest peptides present in the membranes (bands A, 1, 2 and 3). Certain smaller peptides (bands 4, 5 and 9) were the predominant species labeled at this time. By 24 h all peptides showed significant incorporation. With maturation of the red cells, label largely disappeared from bands A, 9 and several smaller peptides; this was confirmed by finding that the peptides are virtually absent from mature circulating erythrocytes. These data are interpreted as showing that red cell membrane proteins are synthesized asynchronously during the life cycle of the erythrocyte; the largest peptides are made predominantly in the earlier marrow stages of development, while certain of the smaller peptides are still being synthesized in the reticulocyte stage. Several membrane proteins appear to be specific to the reticulocyte and are lost during the process of cell maturation in the circulation.

Anatomical observations have indicated a decrease of marrow cellularity with age, but these changes are not associated with anemia in the healthy geriatric patient. Aged patients with refractory anemia should be studied by utilizing red cell volume (MCV) and red cell heterogeneity (RDW). A classification with these indices initially can separate the anemias for a more fruitful investigation. By old age the anemias of hereditary red cell membrane or hemoglobin disorders should be known to the patient. In the absence of tumor, elderly patients have an increasing frequency of refractory anemias that can be called preleukemia or myelodysplastic syndrome. Morphological observations have emphasized the importance of abnormal megakaryocytes and platelets in all phases of preleukemia, and these cytologic changes should be used to guide the physician in the early diagnosis of the syndrome complex. This group of refractory anemias have a limited survival, but nonspecific marrow stimulation can be effective and should be tried. With a more complete classification of the chromosomal abnormalities in the myelodysplastic syndrome, a more accurate prognosis can be anticipated. The anemias of marrow aplasia and ineffective iron utilization (anemia of chronic disease) are found frequently in the elderly, and the physician may offer more effective therapy by an early diagnosis.

During the past 9 years, 43 adult patients with severe aplastic anaemia have been treated with a combination of 3 alpha etiocholanolone and nandrolone decanoate in an uncontrolled pilot study. Eleven patients were considered acute and the remainder as chronic severe aplasia. 50% (22 patients) had a haematopoietic recovery and 40% have had a sustained remission varying from 1.5 to 8 years. Three patients who did not respond to 3 alpha etiocholanolone had a haematologic response when treated with the isomer 3 beta etiocholanolone. The recovery did not appear to be associated with age or duration of marrow aplasia. In view of the reproducible chemical structure of these androstanes, we believe this group of steroids should be evaluated further in the treatment of severe aplastic anaemia.