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PubMed2001

Prolonged bone marrow failure with monosomy 7 after engraftment failure following bone marrow transplantation.

A patient with acute myelogenous leukemia developed prolonged bone marrow failure along with the monosomy 7 chromosome abnormality. The patient had undergone bone marrow transplantation with CD34+ selection following induction failure. However, she then suffered engraftment failure and long-term pancytopenia. Her white blood cell count gradually increased with supportive therapy including granulocyte colony-stimulating factor (G-CSF), and chromosomal analysis of bone marrow cells revealed an abnormal karyotype. Thirty months after the bone marrow transplantation we observed monosomy 7 together with the existing chromosomal abnormality in the patient's bone marrow cells. It has been reported that some patients with idiopathic and posthepatitis aplastic anemia develop clonal disorders such as myelodysplastic syndrome/acute myelogenous leukemia with monosomy 7. The findings in our case suggest that the appearance of monosomy 7 in patients with aplastic anemia may be caused by prolonged low-level hematopoiesis, with or without G-CSF stimulation.

Adolescent↗
PubMed1981

Long-term survival of murine allogeneic bone marrow chimeras: effect of anti-lymphocyte serum and bone marrow dose.

Graft-vs-host disease (GVHD) and failure of donor stem cells to engraft permanently are two major obstacles to successful bone marrow transplantation. We evaluated the effect of a single large dose of anti-lymphocyte serum (ALS) on mice receiving various numbers of H-2 incompatible bone marrow cells. Most animals receiving lethal total body irradiation (TBI) and allogeneic marrow died within 45 days due to GVHD, A/J (H-2a), CBA/J (H-2k), and DBA/1J (H-2q) mice that were given ALS 6 to 24 hr before TBI and C57BL/6 (B6, H-2b) bone marrow 24 hr after irradiation survived in good health for more than 200 days. This result compared quite favorably with mice that received anti-Thy 1.2 and C-treated B6 bone marrow (90% survival at 100 days, 50% survival at 200 days). Engraftment of the allogeneic marrow was dose dependent. At 100 days after TBI, about 30% of the A/J mice given 2 x 10(6) bone marrow cells were complete chimeras, i.e., donor H-2 antigens could be detected on greater than 85% of the peripheral blood mononuclear leukocytes of these mice. However, at a dose of 1 x 10(7) B6 bone marrow cells, 95% of the A/J mice were complete chimeras. Spleen and bone marrow from B6 leads to A/J chimeras and B6 leads to CBA chimeras were unable to induce lethal GVHD in TBI-treated mice that were syngeneic to the recipient. However, these cell preparations caused lethal GVHD in third party mice indicating that the lack of alloreactivity was specific to the strain in which the unresponsiveness was originally induced.

Animals↗
PubMed1982

Bone marrow reconstitution of lethally irradiated canines using autologous bone marrow fractions obtained by counterflow centrifugation-elutriation.

Canine bone marrow fractionated by counterflow centrifugation-elutriation results in three areas of nucleated cell recovery. Fraction 1 accounts for 50% of the total nucleated cells and 25-40% of the total recovered CFU-GM activity. Fraction 2 contains less than 2% of the total nucleated cells and less than 0.2% of the CFU-GM activity. Fraction 3 accounts for approximately 50% of the total nucleated cell recovery and 60-75% of the total recovered CFU-GM activity. Animal survival was not directly correlated with the levels of CFU-GM activity in the transfused fractions. Autologous infusion of these fractions into irradiated canines (9 Gy, 0.1 Gy/min) resulted in distinct survival profiles. Canines receiving autologous fraction-2 cells showed no haematological reconstitution, with death occurring on days 10-11 post-irradiation. Canines receiving autologous fraction-3 cells showed limited myeloid repopulation of both the bone marrow and peripheral blood with a mean survival time for 24 d. Canines receiving autologous fraction-1 cells showed complete haematological reconstitution after 48 d and long-term survival. The data may indicate a separation or enrichment of pluripotential stem cells (fraction 1) from committed myeloid progenitor cells (fraction 3).

Animals↗
PubMed1989

Granulocyte colony-stimulating factor stimulates recovery of granulocytes in patients receiving dose-intensive chemotherapy without bone marrow transplantation.

Bone marrow colony-stimulating factors (CSF) ameliorate hematologic toxicity of standard chemotherapy regimens and may allow relatively safe use of intensive and more efficacious doses of anticancer drugs. Twenty-four patients with cancers for which no standard regimens were likely to be effective received repeated courses of a combination of cisplatin (150 mg/m2), etoposide (1,500 mg/m2), and cyclophosphamide (5,000 mg/m2) at doses for which bone marrow transplantation is usually used. A total of 10 patients received escalating doses of recombinant human granulocyte CSF (rhG-CSF); 11 patients receiving identical chemotherapy and supportive therapy without rhG-CSF served as controls for the first cycle of therapy. Five of these patients and 3 additional patients also served as their own controls, receiving rhG-CSF for all cycles after the first. No patient received bone marrow transplantation. rhG-CSF shortened the median duration of severe granulocytopenia (less than or equal to 100/mm3) in a dose-related fashion (P less than .03; Kruskal-Wallis test). Patients not receiving rhG-CSF had a median of 8.5 days of granulocytopenia. Those receiving 40 micrograms/kg of rhG-CSF for approximately 20 days from the third day after chemotherapy had a median of 7.0 days (P less than .23) and those receiving 60 micrograms/kg had a median of 5.5 days (P less than .007) of granulocytopenia. An rhG-CSF dose of 20 micrograms/kg had no effect. Recovery to a granulocyte count of at least 500/mm3 took a median of 12 days in the control group and 8 days (P less than .03) in patients receiving rhG-CSF at a dose of 60 mg/kg. The duration of antibiotic therapy (a median, 9.0 days v 5.0 days) was shortened with the two higher and effective doses of rhG-CSF compared with control patients. The duration of hospitalization (median of 20 days v 19 days) was not shortened. These findings that rhG-CSF decreases the risk of granulocytopenia associated with this particular dose-intensive chemotherapy regimen therapy administered without bone marrow transplantation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Use of a licensed electrolyte solution as an alternative to tissue culture medium for bone marrow collection.

Bone marrow for transplantation is traditionally collected into tissue culture medium with heparin. A licensed electrolyte solution (Plasma-Lyte A [PLA]) was used as a substitute for tissue culture medium in the harvesting of 28 bone marrows, 17 autologous and 11 allogeneic, which were subsequently transplanted. Data that were analyzed from the 25 evaluable patients consisted of the numbers of cells and colony-forming units in the transplanted marrow as well as the time to neutrophil and platelet engraftment. These results were compared with those in the 30 (26 evaluable) preceding transplanted marrows that were collected into a tissue culture medium (RPMI-1640 [RPMI]). The autologous marrow transplant patients in both the PLA and RPMI groups reached a neutrophil count of > or = 0.5 x 10(9) per L a mean of 19 days following transplantation. The patients who underwent transplantation with allogeneic bone marrow collected in RPMI achieved > or = 0.5 x 10(9) per L of neutrophils an average of 20 days following transplantation, while those who received marrow collected in PLA achieved engraftment of neutrophils to that level in a mean of 21 days. Because in vitro and in vivo results with RPMI and PLA are similar in this study, further work using a licensed solution for clinical bone marrow transplantation is indicated.

Adolescent↗
PubMed2000

Bone marrow manifestations of infections and systemic diseases observed in bone marrow trephine biopsy review.

Bone marrow modifications resulting from infections and systemic diseases can be studied by analysis of morphology and aetiology. Two types of lesions or modifications can be observed, those occurring in the connective tissue comprising inflammatory processes, acute and chronic, as well as immune reactions, and those involving the normal haematopoietic cell lines, with possible hyperplastic or aplastic changes in one or more cell lines. The main lesions are described (oedema, haemorrhage, necrosis, suppuration, granulomas, lymphoid nodules and hyperplasia, immunoblastic or plasmacytic hyperplasia), as well as the main aetiologies. In association, the three main haematopoietic cell lines show hyperplasia, hypoplasia, aplasia of one or all of the cell lines, sometimes with dysmyelopoiesis. The stroma and vessel reactions comprise myelofibrosis, gelatinous transformation or amyloid deposits. The methods for identifying aetiological agents are emphasized. It should also be stressed that malignant neoplasias of different types involving the bone marrow can be responsible for such inflammatory or immune reactions.

Bacterial Infections↗
PubMed2000

Bone marrow and peripheral blood leptin levels in lymphoproliferative diseases--relation to the bone marrow fat and infiltration.

Leptin is a nonglycosylated protein produced mostly by adipocytes. The role ofleptin in body weight regulation through its anorectic effect in hypothalamus is very well known. Less known are other leptin effects such as the stimulation of hematopoesis and some parts of immunity system. The role of leptin in the pathogenesis of some malignant tumors is discussed. Only a little is known about bone marrow adipocyte leptin production. We examined leptin concentrations in the sera from peripheral blood and bone marrow, the percentage of bone marrow fat, the degree of bone marrow infiltration, the body mass index (BMI) in 42 patients with lymphoproliferative diseases. We found that bone marrow has significantly lower leptin levels (6,6+/-10,9 ng/ml) than peripheral blood (9,1+/-11,5 ng/ml) (p < 0.0001). Bone marrow and peripheral blood leptin levels have also a significant thin correlation (r = +0.91, p < 0.0001). Bone marrow (r = +0.55, p < 0.0005) and peripheral blood (r = +0.52, p < 0.0005) leptin concentrations are significantly correlated to BMI. Blood serum leptin (r = +0.46, p < 0.003) and bone marrow leptin (r = +0.40, p < 0.01) are related to the bone marrow fat percentage. In addition we found a negative correlation of blood serum leptin (r = -0.59, p < 0.0001) and bone marrow leptin (r = -0.42, p < 0.005) to bone marrow malignant infiltration. When we divided the patients into groups with bone marrow infiltration more than 10% and without or less than 10% infiltration, the first group had significantly lower peripheral blood (p < 0.001) and bone marrow (p < 0.02) leptin. We also confirmed a relation of bone marrow fat and infiltration (r = +0.49, p < 0.001). Our results suggest a relationship among leptin levels in blood or bone marrow and bone marrow infiltration in lymphoproliferative diseases. This fact needs further investigation and an evaluation of its application in clinical practice.

Adipose Tissue↗
PubMed1997

[Relationship between the presence of side-holes in bone marrow aspiration needle and the number of harvested bone marrow mononuclear cells].

The aim of this study was to evaluate the yield of nucleated cells in bone marrow harvested by means of Downs' Islam aspiration needles with or without side-holes. Twenty marrow donors for HLA identical sibling transplants were studied. Bone marrow nucleated cells were harvested 50 ml in the right iliac bone with a Downs' Islam aspiration needle with or without side-holes and 50 ml in the left with another kind of needle by means of 5 ml aspirations in each donor. There were no significant difference between the number of nucleated cells by means of Downs' Islam aspiration needles with and without side-holes by cross-over analysis. All nucleated cell counts were 33.06 +/- 12.93 x 10(3)/microliter (mean +/- standard deviation) by means of the needle with side-holes and 32.90 +/- 15.25 x 10(3)/microliter by means of the needle without side-holes. The Downs' Islam aspiration needle without side-holes seems to be better in bone marrow harvest from normal volunteers than that with side-holes, because the former may be stronger than the latter.

Adolescent↗
PubMed1991

High-dose therapy and autologous peripheral stem cell transplantation for patients with bone marrow metastases and relapsed lymphoma: an alternative to bone marrow purging.

Throughout a 4-year period, we reinfused autologous peripheral stem cells rather than purged autologous bone marrow following high-dose therapy to 57 patients with relapsed lymphoma and bone marrow metastases. Approximately 7 x 10(8) circulating mononuclear cells/kg patient weight were collected for each patient with 6-19 4-h apheresis procedures while hemopoiesis was unperturbed. Following collection, the cells were cryopreserved. Administration of high-dose therapy, which included either combination chemotherapy or combination chemotherapy plus total body irradiation, was followed by i.v. administration of the thawed autologous stem cells. The rate of hemopoietic recovery varied with the specific high-dose therapy administered. Sixty-two percent of 50 evaluable patients had a clinical complete response. The actuarial event-free survival for these patients 4 years after transplantation was 30%, and the projected survival at 4 years was 51%. Patients with relapsed lymphoma and bone marrow metastases who receive high dose therapy followed by peripheral stem cell transplantation can experience long-term event-free survival. Whether similar patients would fare as well with the same high-dose therapy followed by a purged autologous bone marrow transplantation would require a randomized prospective study.

Adult↗
PubMed1981

Granulocyte progenitor compartments after allogeneic bone marrow grafts.

Bone marrow granulocyte colony forming cells (CFU-C) were measured in HLA compatible sibling donor-recipient pairs. The regeneration of granulocytes and CFU-C compartments were also studied in order to evaluate haemopoietic recovery. The number of nucleated bone marrow cells in the donation was 23 +/- 4 X 10 cells, which recipients received (3.5 +/- 0.4) X 10(8) nucleated cells/kg and (1.19 +/- 0.32) X 10(5) CFU-C/kg. This produced a bone marrow reconstitution of (67 +/- 26) X 10(5) CFU-C/kg by day 30. There was a significant correlation between CFU-C/kg and (1) granulocyte count on day 30 (P equal less than 0.05) and (2) the first day of reappearance of neutrophils in the blood (P equal less than 0.05). These results indicate that the speed and completeness of granulocyte regeneration can be predicted by measurement of the size of the CFU-C inoculant in the bone marrow graft.

Adolescent↗
PubMed1976

Colony forming units (CFU) in bone marrow associated with heterotopic bone formation by epithelial cells grafted in mice.

The presence of bone marrow accompanying heterotopic bone induction in mice did not increase the number of endogenous spleen colonies. However, such bone marrow, as judged by the ability to form exogenous spleen colonies, contains colony-forming cells (CFC). No significant difference was found between the concentration of CFC in the induced and in the femoral bone marrow. This indicates a qualitative similarity between these two types of bone marrow inasfar as hemopoietic activity is concerned.

Animals↗
PubMed1996

[Donor selection for allogenic bone marrow transplantation from 1991 to 1995. (The Prague Center for Bone Marrow Transplantation)].

BACKGROUND: The prerequisite of successful transplantation of haematopoietic stem cells is to find a suitable, i.e. HLA matched bone marrow donor. In the submitted paper the authors give an account of the strategy of selection of bone marrow donors, as practised by the Prague transplantation group. METHODS AND RESULTS: In 1991 to 1995 (end of first quarter) the authors sought suitable bone marrow donors for 421 patients where an allogenic bone marrow transplantation was indicated. During that period 95 transplantations were performed (22.5% of all indicated cases), incl. 82 from siblings (86.3%) of the implemented allogenic bone marrow transplantations). A HLA matched donor from the wider family circle was selected for 15 donors, transplantation were performed in 6 patients (6.4% of the implemented allogenic bone marrow transplantations). An unrelated bone marrow donor was sought for 41 patients as no donor was found in the wider family. Transplantation was implemented in 7 of these patients (7.3% of the implemented transplantations. CONCLUSIONS: With the increasing experience of our transplantation centre, no doubt, the ratio of other than sibling transplantations of bone marrow will increase. At present it accounts for 13.7%. The task of our HLA group must be selection of donors matched as well as possible with the recipient according to all available tests of tissue compatibility - from the wider family circle as well as from the register of unrelated donors.

Bone Marrow Transplantation↗
PubMed2001

Larger numbers of CD4(bright) dendritic cells in donor bone marrow are associated with increased relapse after allogeneic bone marrow transplantation.

Relapse is the major cause of death after allogeneic bone marrow transplantation (BMT). This study tested the hypothesis that the numbers of donor mononuclear cells, lymphocytes, and CD34(+) cells influence relapse and event-free survival (EFS) after BMT. The study population consisted of 113 consecutive patients with hematologic malignancies who underwent non-T-cell-depleted BMT from HLA-matched siblings. Sixty-four patients had low-risk diagnoses (ALL/AML CR1, MDS RA/RARS, and CML CP1); 49 patients had high-risk diagnoses (all others). CD34(+) cells, T cells, B cells, natural killer cells, monocytes, and a rare population of CD3(-), CD4(bright) cells in the allografts were measured by flow cytometry. The CD3(-), CD4(bright) cells in bone marrow had the same frequency and phenotype as CD123(bright) type 2 dendritic cell (DC) progenitors, and they differentiated into typical DCs after short-term culture. Cox regression analyses evaluated risk strata, age, gender, and the numbers of nucleated cells, CD3(+) T cells, CD34(+) hematopoietic cells, and CD4(bright) cells as covariates for EFS, relapse, and nonrelapse mortality. Recipients of larger numbers of CD4(bright) cells had significantly lower EFS, a lower incidence of chronic graft-versus-host disease (cGVHD), and an increased incidence of relapse. Recipients of larger numbers of CD34(+) cells had improved EFS; recipients of fewer CD34(+) cells had delayed hematopoietic engraftment and increased death from infections. In conclusion, the content of donor CD4(bright) cells was associated with decreased cGVHD and graft-versus-leukemia effects in recipients of allogeneic bone marrow transplantation, consistent with a role for donor DCs in determining immune responses after allogeneic BMT.

Adult↗
PubMed1993

Amplification of a Y-chromosomal DNA sequence by the polymerase chain reaction for documentation of residual recipient cells in small samples from bone marrow, peripheral blood and cerebrospinal fluid after bone marrow transplantation.

The long arm of the human Y-chromosome contains about 800 to 5000 copies of the tandemly repeated DNA sequence DYZ1. A major part of the repeating unit (pHY10) has been cloned and sequenced. Primers were designed to match a part of this repeat sequence for the amplification of a 154 bp fragment spanning the EcoRI restriction site of the unit. Typical dilution experiments showed that this polymerase chain reaction (PCR) method allows the detection of 5 to 10 male cells among 100,000 female cells, or in 500 microL of cerebrospinal fluid containing only one cell per microL. In addition, the quality of the DNA used for the amplification reaction is less critical, thus allowing analysis of long-term stored samples such as bone marrow smears or dried blood stains spotted onto filter paper, which might contain partially degraded DNA. We applied this technique to detect residual host cells in the clinical setting of human sex-mismatched bone marrow transplantation (BMT). Fourteen patients, receiving transplantations because of leukemias could be supervised so far. Throughout the whole period of monitoring (days +14 until +911 post BMT; median: 160 days), residual host cells were detected in all but three patients. Persistence of host cells in the early phase post-BMT was mostly transient and probably due to long-term surviving host T-lymphocytes. Reappearance of host cells several months after BMT is highly suspicious of relapse from the underlying malignancy. Due to its high sensitivity, PCR is a valuable tool in monitoring the switch from recipient to donor cell population.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1989

[Bone marrow necrosis as a manifestation of leukemic relapse in a patient with bone marrow transplant].

A case of bone marrow necrosis (BMN) in transplanted acute lymphoblastic leukaemia (ALL) is presented. The propositus is a 16 year-old boy with L-2 type ALL on whom allogeneic bone marrow transplantation (BMT) had been performed after the second relapse. He was admitted to hospital at 415 after BMT with fever, malaise and hip pain. One week later he had aplasia without blast cells. Scanty cellularity with necrobiosis was found in bone marrow aspirates; bone marrow biopsy confirmed the suspicion of BMN. Osseus scintigraphy with 99-Tc-diphosphonate showed poor, irregular distribution. Steroid therapy was followed by a favourable response. Peripheral blast cells appeared two weeks later, and the relapse was confirmed by bone marrow aspiration. Chemotherapy was started, but the patient died on day 467 after BMT. BMN has been reported in ALL at onset, in relapses, after chemotherapy and as necropsy finding; however, it had not been found in patients subjected to BMT. The experience of these Service was revised, this being the only case of 140 patients subjected to BMT who presented such severe complication.

Adolescent↗