A comparison of peripheral blood and buffy coat smear examination for the prediction of bone marrow relapse of acute lymphoblastic leukaemia in childhood

In an attempt to see if buffy coat smear examination might be an alternative to bone marrow aspiration for predicting relapse, 98 consecutive bone marrow aspirates from 96 children with acute lymphoblastic leukaemia were examined blind with buffy coat and peripheral blood from the same patients. The 28 bone marrow aspirates from children no longer on treatment were all normal, and routine aspirates would appear unjustified in these patients. Eight of the remaining marrows showed relapse, but only three were not predicted from the peripheral blood and buffy coat. In no case was buffy coat superior to peripheral blood in the detection of bone marrow relapse. Routine bone marrow aspirates are an inefficient way of diagnosing relapse in acute lymphoblastic leukaemia in childhood, despite their precision, and a prospective study is needed to determine their value.     

Comparable Outcomes of Allogeneic Peripheral Blood versus Bone Marrow Hematopoietic Stem Cell Transplantation in Major Thalassemia: A Multivariate Long-Term Cohort Analysis

Allogeneic hematopoietic stem cell transplantation (HSCT) currently is the only available curative option for transfusion-dependent thalassemia. Peripheral blood is a more convenient source for HSCT in comparison with bone marrow. Information about the relative success of transplantation with these 2 graft sources would help physicians and patients choose between them. The aim of this study was to evaluate the pros and cons of using peripheral blood instead of bone marrow as the graft source in thalassemia transplantation. We analyzed the transplant results of 567 transfusion-dependent thalassemia patients who received a transplant between 1998 and 2015 considering their stem cell source as a comparative variable. In multivariate Cox analysis the survival advantage for bone marrow compared with peripheral blood was not significant after adjusting for sex, age, and hepatic fibrosis presence. Rejection incidence was significantly lower in patients who used peripheral blood as their graft source. Acute and chronic graft-versus-host disease were more frequent in peripheral blood transplants, but the difference was not statistically significant. This study shows that peripheral blood could be an alternative stem cell source in patients undergoing allogeneic HSCT for thalassemia.     

Numbers and phenotype of lymphocytes emigrating from sheep bone marrow after in situ labelling with fluorescein isothiocyanate

In normal young lambs the bone marrow was selectively labelled with fluorescein isothiocyanate by a temporary perfusion of one hind-leg. One day later, the incidence of bone marrow emigrants in different lymph nodes, spleen, Peyer's patches, thymus, non-perfused bone marrow and blood was determined. The emigrants were also phenotyped by the use of monoclonal antibodies and classified into monocytes or lymphocyte subsets. Large numbers of lymphocytes left the bone marrow of the perfused leg during 1 day. Considerable numbers of cells migrated to other bone marrow compartments. Varying numbers of mononuclear emigrants were found in peripheral lymphoid organs, with labelling indices ranging from 1.06% in the blood to 0.004% in the thymus. In the spleen, comparable numbers of B- and T-lymphocyte emigrants from the bone marrow were found, whereas in the blood, lymph nodes and jejunal Peyer's patches many more emigrants were T lymphocytes than B lymphocytes. In the prescapular lymph nodes, for instance, 90.4% of emigrants were T cells but only 9.6% were B cells. Based on the large numbers of lymphocytes emigrating from the bone marrow, their phenotypes and their entry into other bone marrow compartments, it it can be concluded that the bone marrow of young lambs is an integral part of the migratory route of lymphocytes.     

Hemopoietic progenitor cells in the blood as indicators of the functional status of the bone marrow after total-body and partial-body irradiation: experiences from studies in dogs

The granulocyte-macrophage colony-forming cells (GM-CFC) were studied in the blood of dogs to evaluate their relationship to the bone marrow GM-CFC under normal conditions and their involvement in hemopoietic regeneration after different types of exposure to ionizing radiation. The GM-CFC could be defined as regular blood elements showing characteristic levels of their concentration in individual dogs in the range from 20 to 300 cells per ml. In relative terms, the GM-CFC numbers present in the whole blood of normal dogs were found to be on the order of 0.1% of the GM-CFC numbers present in the bone marrow. A small fraction of the GM-CFC population in the bone marrow, i.e., about 1%, can be mobilized into the peripheral blood within three h by intravenous injection of dextran sulfate (DS). These cells are characterized by a small size and a low S-phase fraction similar to the GM-CFC that are normally present in the blood. Total-body irradiation with single doses of 0.8 Gy and more caused a characteristic pattern of sequential changes in the blood GM-CFC concentration that were related to the recovery of the bone marrow GM-CFC population. The blood GM-CFC concentration showed an extreme depression within the first 15 days, a transient increase from day 17 to day 35 and remained at subnormal values for several weeks and months. The regeneration of the GM-CFC population in the bone marrow that could be mobilized into the blood by DS was similarly delayed as the recovery of the blood GM-CFC values. In dogs which were kept under continuous radiation exposure (0.019 Gy/day) causing permanent damage to the hemopoietic system, the GM-CFC numbers in the blood remained permanently depressed. Partial-body irradiation of dogs with a myeloablative dose (11.7 Gy) given to the anterior part of their body was followed by sequential changes in the blood GM-CFC concentration specific for this type of exposure. The pattern of changes was determined by direct radiation effects, the compensatory responses in the protected bone marrow and the regeneration events in the irradiated bone marrow. On the other hand, it could be shown that the repopulation and the restoration of the hemopoietic tissue is initiated by the seeding of hemopoietic cells (including GM-CFC) from the protected marrow.     

Normal structure, function, and histology of the bone marrow

While a complete blood count provides information regarding possible treatment-related effects reflected in the peripheral blood, morphological evaluation of bone marrow cytology and paraffin sections provides information about bone marrow tissue architecture that otherwise would be missed by examination of peripheral blood alone. In decalcified, paraffin-embedded, hematoxylin and eosin (H&E)-stained sections of bone marrow, the more mature stages of the erythroid and myeloid cells, adipocytes, mast cells, and megakaryocytes can be identified, but lymphoid cells as well as immature progenitor cells can not be reliably identified. The quality of the marrow sections is governed by numerous variables related to specimen collection and processing and must be considered. In addition to discussing normal structure, function, and histology of bone marrow, methods for preparation and evaluation of bone marrow are presented.     

Marrow uptake index (MUI): a quantitative scintigraphic study of bone marrow in aplastic anaemia

Aplastic anaemia affects the entire bone marrow. Current methods of assessment of bone marrow function, like bone marrow biopsy or peripheral blood examination are either invasive or inadequate and cannot be expected to represent fully the changes in the entire bone marrow tissue. This prospective study was undertaken to develop and standardise a new Nuclear Medicine technique called 'Dynamic Bone marrow Imaging'. Eleven patients and ten controls were studied. Serial images of the pelvis were obtained in frame mode following intravenous injection of 185-370 mBq of 99mTc S. Colloid, and an index, called the Bone Marrow Uptake Index (P) was calculated by taking into consideration the time activity curve obtained over the iliac crest. This was followed by static imaging of the entire bone marrow in all cases. It was possible to obtain excellent information regarding topographic distribution of bone marrow as well as detect early changes in bone marrow function following treatment. An attempt was also made to correlate bone marrow cellularity as obtained by bone marrow biopsy with the results of dynamic bone marrow scintigraphy. On the basis of the encouraging results obtained in the present study, the authors feel that dynamic bone marrow imaging is an excellent technique for the objective evaluation of bone marrow in aplastic anaemia. Aplastic anaemia affects the entire bone marrow tissue. Although much progress has been made in the management of this disease, many aspects of it await better understanding. There is almost total lack of knowledge regarding the distribution of functioning marrow in various phases of aplastic anaemia, such as in relapse and remission. Current methods of assessment of marrow function rely mainly on bone marrow biopsy and peripheral blood examination. Bone marrow biopsy is invasive and cannot be expected to represent fully the changes in the entire tissue. Changes in peripheral blood picture lag behind the changes in the bone marrow. Thus, there is a need for an investigation which is safe, simple, sensitive, non invasive and capable of assessing the global function of bone marrow. Radio-nuclide imaging of bone marrow requires labelling of one or more components of this widely dispersed tissue. The reticuloendothelial and erythropoietic components can be labelled with radio-colloids and radio-iron respectively. Experimental studies have shown that the reticuloendothelial and erythropoietic elements are invariably found together in the marrow and have similar distribution. This report is based on a prospective study of bone marrow function in patients with aplastic anaemia, using 99mTc. Sulphur colloid.     

Peripheral eosinophilia camouflaging anaplastic large cell lymphoma

Eosinophilia is a nonspecific laboratory finding, often noted incidentally during routine blood analysis. When persistent, eosinophilia can herald an underlying parasitic infection, drug reaction or less commonly, a neoplastic process. Anaplastic large cell lymphoma (ALCL) and tissue eosinophilia has been described; however, such cases have not displayed marked leukocytosis with eosinophilia. This article reports a patient presenting with marked leukocytosis with profound peripheral eosinophilia initially thought to be related to a chronic myeloproliferative disorder, likely chronic eosinophilic leukemia. After further diagnostic evaluation, ALCL was noted in the bone marrow, masked by the myeloid hyperplasia and eosinophilia. This case emphasizes the importance of a full diagnostic workup for T-cell malignancies, including ALCL rather than focusing on the far less common eosinophilia-associated myeloid malignancies in the clinicopathologic setting of marked eosinophilia. Moreover, bone marrow involvement by ALCL is exceedingly rare and when noted, presents as one or more localized lytic lesions. This is the first reported case of ALCL primarily involving bone marrow without radiographic evidence of lytic bone lesions.     

Immunological capacity of the chicken embryo. I. Relationship between the maturation of lymphoid tissues and the occurrence of cell-mediated immunity in the developing chicken embryo.

In an investigation of the ontogeny of lymphoid tissue in chick embryos to relate maturation of lymphocytes with immunological competence, the numbers and sizes of lymphocytes were determined in the thymus, bursa of Fabricius, spleen, femoral marrow and peripheral blood of embryos from the 12th to 21st day of incubation, and in 6-day-old chicks. Results showed the thymus to be the first fully developed and most active lymphocytopoietic organ, followed by the bursa. The bone marrow was not lymphocytopoietic; the spleen and bone marrow were mainly granulocytopoietic and erythropoietic; some morphological differences between thymic and bursal lymphocytes were shown by light microscopy. It appears that in embryos and young chicks the lymphocytes are derived from the thymus and bursa, but not the bone marrow. In tests of immunological competency, cells of the thymus, bursa, spleen, bone marrow and peripheral blood from 12--21-day-old embryos and 6-day-old chicks were transferred to chorioallantoic membranes of 12-day-old recipient embryos. There were distinct differences between the ability of various lymphoid tissues to induce formation of chorioallantoic pocks or splenic enlargement. The thymus, spleen and peripheral blood elicited both lymphocytic pocks and splenomegaly, the bursa elicited splenomegaly only, and the bone marrow was ineffective. The bone marrow, however, induced formation of nonlymphocytic pocks. It is concluded that the immunological activity of the chicken embryo is primarily effected by the thymus and bursa and that cell-mediated immunity appears in the 2nd week of incubation.     

Bone marrow micrometastasis in breast cancer: review of detection methods, prognostic impact and biological issues

Immunocytochemical detection of disseminated tumour cells in the bone marrow of patients with primary breast cancer at surgery has been shown to be an independent prognostic factor in single institutional studies and in a large pooled analysis. However, bone marrow sampling and assessment of disseminated tumour cells is not a routine procedure in the clinical management of patients with breast cancer, but will certainly play a role in the near future for risk stratification and monitoring of therapeutic efficacy. Accurate identification of disseminated tumour cells in bone marrow must be based on standardised methodologies and procedures. This review describes these methodologies and the standardised morphological criteria used for disseminated tumour cell detection. The prognostic value of circulating tumour cells detection in peripheral blood is demonstrated in patients with metastatic disease but remains to be substantiated at early stage. The significance of disseminated tumour cells in bone marrow and in the blood for the prediction of response to therapy is briefly summarised. Finally, this review addresses the main biological questions raised by disseminated tumour cells, in particular understanding tumour dormancy and identifying metastatic stem cells.     

Acute myelofibrosis with peripheral myeloblastosis: an acute myeloproliferative disorder

Acute myelofibrosis is an uncommon fulminant disorder characterized by pancytopenia, premature myeloid elements in the peripheral blood, and bone marrow fibrosis. We report the case of a 59-year-old man who had acute myelofibrosis and peripheral myeloblastosis clinically suggesting the diagnosis of acute granulocytic leukemia. The disease was unresponsive to cytotoxic drugs or androgens and the patient died five months later. The association of bone marrow fibrosis with large numbers of myeloblasts in the peripheral blood has rarely been reported and suggests a spectrum of morphological changes in acute myeloproliferative disorders, analogous to the merging of chronic myeloproliferative disorders into one another and into leukemic blast crisis.     

The origin and in vivo significance of murine and human culture-expanded endothelial progenitor cells

In adults highly purified populations of early hematopoietic progenitors or cells derived from ex vivo expanded unmobilized human peripheral blood mononuclear cells contribute to new blood vessel formation. However, the source of these culture-expanded endothelial progenitor cells (CE-EPCs) remains controversial. We demonstrate that ex vivo expansion of unmobilized human peripheral blood generated CE-EPCs with similar numbers, kinetics, and antigen expression profile as compared to plating unfractionated CD34(+)/lin(-)-enriched bone marrow mononuclear cells. Both CE-EPC populations uniformly co-expressed myeloid and endothelial markers, suggesting that peripheral blood progenitor enumeration does not correlate with the numbers of early outgrowth CE-EPCs. Using purified myeloid subpopulations obtained from mice harboring the lacZ transgene driven by an endothelial-specific promoter, we showed that the immature myeloid lineage marker CD31(+) cells generated CE-EPCs with fourfold greater frequency than mature myeloid populations. Biphenotypic cells co-expressing myeloid/endothelial antigens were not detected in circulating human or murine peripheral blood or bone marrow but were associated with murine tumors. Unlike CE-EPCs, CD14(+) leukocytes admixed within tumors did not generate vWF-positive blood vessels during a similarly defined period of tumor growth, but some leukocytes up-regulated the endothelial marker VE-cadherin. Taken together, the data suggest that the local neovascular microenvironment may facilitate vasculogenesis by promoting endothelial differentiation and that CE-EPCs may accelerate such vasculo-genesis.     

Kinetics and mechanisms of recombinant human granulocyte-colony stimulating factor-induced neutrophilia.

Recombinant human granulocyte colony stimulating factor (G-CSF) injected intravenously in rats causes an initial peripheral neutropenia between 3 and 15 minutes and a subsequent neutrophilia beginning at 0.5 hours, peaking between 12 and 24 hours, and subsiding to normal between 30 and 36 hours. A striking hypersegmentation of neutrophil nuclei is observed between 30 and 48 hours. The bone marrow at 4 and 12 hours exhibits an increase in number, mitoses, size, and cytoplasmic granulation of myeloblasts and promyelocytes but a decrease in mature neutrophils, demonstrating that G-CSF acts not only as a mitogen and growth factor for early cells in the myeloid series but also as a releasing factor for mature marrow neutrophils. The bone marrow at 48 hours contains slightly increased numbers of myelocytes and metamyelocytes and large numbers of hypersegmented neutrophils. Dexamethasone and gamma-interferon inhibit the magnitude of G-CSF-induced neutrophilia, suggesting that endogenous glucocorticosteroids and gamma-interferon, both which are released along with G-CSF in vivo during endotoxemia, may play a negative feedback role in the endogenous regulation of granulopoiesis. G-CSF may act in concert with other monokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1) to induce the changes in circulating numbers of leukocytes noted during endotoxemia.     

Quantitative problems in bone marrow transplantation by peripheral blood stem cells

Investigation into radiation bone marrow aplasia in mice, guinea pigs, dogs and clinical trials in man presented clear evidence of successful engraftment of autologous or allogeneic peripheral blood stem cells. The quantitative donation problems are discussed arising with the use of continuous cytopheresis to obtain a sufficient quantity of peripheral blood mononuclears (stem cells) for repopulation of aplastic bone marrow. Although bone marrow repopulation is possible by using peripheral blood mononuclears (stem cells) in individual cases, the method can only be used in practice after discovering an appropriate stimulator able to augment several times the number of bone marrow stem cells in the peripheral blood, or a new method for stem cell multiplication in vitro.     

Analysis of hematopoietic and lymphopoietic tissue during a regenerative aplastic crisis induced by avian retrovirus MAV-2(O)

Infection of 10-day-old chickens with an avian osteopetrosis virus resulted in a severe regenerative aplastic crisis. Hematopoietic and lymphopoietic tissues of chickens infected with myeloblastosis-associated virus (of subgroup B, inducing osteopetrosis, MAV-2(O] were analyzed for integrated and unintegrated viral DNA sequences, cell population shifts, weight changes, and morphological alterations. By 6 days postinfection (p.i.), DNA from bone marrow cells and peripheral blood leukocytes (PBL) contained between 0.50 and 0.70 copies of viral DNA per haploid genome. Erythrocytes and splenic leukocytes contained less than 0.10 copies/haploid genome. Granulocytes and precursor mesomyelocytes were absent from bone marrow, but numbers of erythrocytes, erythroblasts, and reticulocytes were normal. By 9 days p.i., bone marrow was severely hypoplastic and both granulopoietic and erythropoietic colonies were depleted. By 12 days p.i., erythrocytes and granulocytes were maximally depressed in peripheral blood and the amount of integrated virus in bone marrow and PBL decreased to less than 0.20 copies/haploid genome. In contrast, erythrocytes contained integrated viral DNA of up to 0.30 copies/haploid genome, indicating infection of erythrocyte precursors. At 18 days p.i., viral DNA was detected only in erythrocytes. Unintegrated viral DNA was not detected in any organs. Anemia was accompanied by splenomegaly and erythrophagocytosis. Viral DNA was never detected in thymus or bursa. Differential counting and flow cytometry of cells from bursa, thymus, and spleen, and of blood lymphocytes did not detect significant population shifts. These results suggest that MAV-2(O) infection of immunocompetent chickens occurs primarily in myelopoietic tissues, and tissues are selectively infected.     

Evaluation of the rat micronucleus test with bone marrow and peripheral blood: Summary of the 9th collaborative study by CSGMT/JEMS·MMS

The mouse has traditionally been used for the micronucleus test, with bone marrow the usual target organ. The aim of the 9th collaborative study by CSGMT was to evaluate the suitability of the rat for the micronucleus test, with bone marrow and peripheral blood as the target organ. Since the rat spleen eliminates circulating micronucleated erythrocytes, a rat peripheral blood micronucleus assay might not be feasible. Thirty-four Japanese laboratories and six overseas laboratories participated in this collaboration, and 40 chemicals were studied. As a rule, rat bone marrow and peripheral blood were analyzed using acridine orange staining. Among 36 mouse micronucleus-positive rat carcinogens, 34 of which had been evaluated by CSGMT, we observed 33 positive and three negative results with rat bone marrow and 30 positive, three equivocal, and three negative responses with rat peripheral blood. Of the two mouse micronucleus-negative rat carcinogens, acrylonitrile was positive in rat bone marrow and 4,4′-methylene bis(2-chloroaniline) was negative in both rat bone marrow and peripheral blood. Two chemicals reported to be mouse micronucleus-negative and rat-positive, azobenzene and Solvent Yellow 14, and one chemical reported to be mouse-positive and rat-negative, 1,2-dimethylhydrazine, gave positive responses in rat bone marrow and peripheral blood. The concordance between bone marrow and peripheral blood with rats was 92%. The concordance between rat and mouse erythrocytes was 88%. We concluded that the rat micronucleus assay, using either bone marrow or peripheral blood, can be used as an alternative to the mouse micronucleus assay. Environ. Mol. Mutagen. 32:84–100, 1998. © 1998 Wiley-Liss, Inc.     

Neutrophil granulocytic cell antigen defined by a monoclonal antibody--its distribution within normal haemic and non-haemic tissue.

Monoclonal antibodies were raised against normal human bone marrow cells. One of the antibodies obtained, monoclonal antibody 3C4 (MA 3C4), the subject of this paper, was characterised by immunofluorescence studies with viable normal peripheral blood and bone marrow cells and by immunoperoxidase studies using paraffin sections. In bone marrow and peripheral blood MA 3C4 reacts selectively with cells of late neutrophilic granulopoiesis (myelocytes, metamyelocytes, and neutrophilic granulocytes). Cells of erythropoiesis, thrombopoiesis and lymphopoiesis are negative. In lymph node and spleen only neutrophils react with MA 3C4. In non-haemic tissue reactivity was seen with epithelial cells of a variety of different gland ducts. Thus the antigen detected by MA 3C4 can serve as a marker for neutrophil differentiation in normal haemopoiesis and as a marker for ductal epithelial cells of a variety of organs within non-haemic tissue. The antigen is formalin-resistant and can be detected in paraffin sections. The antibody thus appears to be a valuable reagent for both haematological research and for routine pathology.     

Evaluation of peripheral blood involvement of mantle cell lymphoma by fluorescence in situ hybridization in comparison with immunophenotypic and morphologic findings.

Mantle cell lymphoma is non-Hodgkin's B-cell lymphoma characterized by the t(11;14)(q13;q32) translocation. Peripheral blood involvement of mantle cell lymphoma is usually associated with a poor prognosis and therefore, its identification is clinically important. In this study, we performed cyclin D1/IgH-probe fusion fluorescence in situ hybridization analysis on 223 peripheral blood samples: 185 from 125 mantle cell lymphoma patients, and 38 normal controls. The cutoff values for the test were established using normal controls. Flow cytometry on peripheral blood and corresponding bone marrow samples was used to evaluate this test. In all, 26% of the 185 peripheral blood samples and 27% of the 161 corresponding bone marrow samples were flow cytometry positive for mantle cell lymphoma. The mean numbers of single and- double-fusion signals and the mean number of CD5/CD19-positive cells, absolute blood lymphocyte count, and white blood cell count were significantly higher in peripheral blood and corresponding bone marrow samples with mantle cell lymphoma-positive flow cytometry. Double-fusion signals were more specific than single-fusion ones. Fluorescence in situ hybridization was far more likely to be positive for mantle cell lymphoma when the peripheral blood and the corresponding bone marrow samples had positive flow cytometry results or morphology (P<0.01). Our study indicates that cyclin D1/IgH-fusion fluorescence in situ hybridization analysis could be used to determine the presence and character of circulating mantle cell lymphoma cells in peripheral blood, thus enhancing our ability to evaluate leukemic mantle cell lymphoma and minimum residual disease.     

Reticulocyte as indication of the erythroid hematopoiesis: reticulocyte fractions in peripheral blood and bone marrow

Reticulocyte fractions of peripheral blood and bone marrow were measured for hematological disease in 235 patients using automated fluorescent reticulocyte analysis of Sysmex R-3000. The comparison with R-3000 and the manual method of bone marrow measurement showed an excellent agreement with a correlation coefficient of r = 0.933. In the ratio of reticulocyte fractions of marrow blood and peripheral blood, the marrow blood rate of reticulocytes, HFR, MFR, and LFR was 3.3, 6.2, 1.6, and 0.9 times higher than the peripheral blood rate, respectively. Cases in which the marrow reticulocyte rate was over ten times higher than the peripheral blood rate were observed in MDS and megaloblastic anemia at ratio of 55% and 100%, respectively. These findings suggest ineffective hematopoiesis in bone marrow. Immature reticulocyte fraction(10% or more) showed an excellent agreement with granulocyte(500/microliter or more) as an indication of the engraftment of allotransplantation of bone marrow, in which the analysis of reticulocyte fractions showed a useful indication of engraftment. In cases of death after bone marrow transplantation unlike in survivors, reticulocyte fractions decreased after engraftment.     

Differences in the Kinetics of Histamine Formation and Granulation of Human Basophilic Cells from Bone Marrow, Peripheral Blood, and Cord Blood

Human bone marrow, cord blood, and peripheral blood contain progenitor cells, which during culture mature to histamine-containing basophilic cells. In bone marrow the histamine content per Alcian blue staining basophilic cell was low before culture. Cultivation of BML cells resulted in increased histamine levels in cultures (P less than 0.05), whereas the basophilic cells did not increase significantly. Cell cultures were stimulated with conditioned medium (CM) produced with allergen-stimulated cells from atopics and from the Mo T leukaemic cell line. Cells from cultures stimulated with CM contained less histamine calculated per basophilic cell than did those from unstimulated cultures (P less than 0.05). There was a significant correlation between the numbers of basophilic cells and the histamine content in cells on day 0 prior to cultivation and after 14 days of cultivation (P less than 0.01 and P less than 0.05 respectively). In cord blood there was a correlation between the numbers of basophilic cells and the histamine levels prior to cultivation (P less than 0.05). During cultivation the number of basophilic cells increased five-fold (P less than 0.02), whereas the histamine levels did not increase resulting in a decreased histamine level per basophilic cell (P less than 0.02). In peripheral blood the basophilic cells contained the highest levels of histamine. The numbers of basophilic cells and their content of histamine showed good correlation both before and after unstimulated and stimulated cultivation (P less than 0.01), whereas unstimulated cultures did not show such correlation. The results indicate the presence of different proportions of progenitor cells in bone marrow, cord blood, and peripheral blood, all with different ability to produce histamine and become granulated basophilic cells.