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PubMed1993

Recovery from diabetes insipidus associated with AML after a BMT conditioning regimen including busulfan.

We describe a patient who, at the onset of acute myelomonocytic leukemia, presented with marked polyuria, polydipsia and laboratory findings consistent with diabetes insipidus (DI). He was treated with vasopressin (DDAVP) with a good response and concurrently induced with daunorubicin and conventional doses of cytosine arabinoside. CR was achieved. The vasopressin requirement decreased progressively, but the patient remained DDAVP-dependent after consolidation treatment. He underwent allogeneic BMT, conditioned with busulfan and cyclophosphamide. By day 15 after BMT vasopressin was no longer required and at a follow-up of 9 months the patient has no evidence of DI. In the absence of specific findings, we think it possible that he had leukemic microinfiltration of the hypothalamic-pituitary area. The drugs used for conditioning may have eradicated CNS disease.

Adult↗
PubMed1993

Mixed chimaerism; detection and significance following BMT.

Residual recipient haematopoietic cells may coexist with donor haemopoietic tissue following BMT. This is known as mixed chimaerism. The incidence of mixed chimaerism varies with the sensitivity of the detection system used; DNA based methodologies are the most sensitive. The influence of mixed chimaerism on leukaemia relapse and graft rejection is unclear. The lineages in which mixed chimaerism occurs may affect outcome.

Anemia, Aplastic↗
PubMed1993

Allogeneic bone marrow transplantation for the treatment of adult acute leukemias.

Allogeneic BMT has been shown to be a highly effective therapy for both AML and ALL. With the availability of unrelated donors, continuing advances in the development of new and more effective transplant regimens, and the identification of agents such as the hematopoietic growth factors, alprostadil, and pentoxifylline to decrease the regimen related toxicities, BMT will become a viable option for a greater number of adults with acute leukemia. The optimal timing for BMT will continue to evolve, but based upon the currently available information, patients age 55 or less with AML with a high probability of relapse based upon cytogenetic abnormalities should be considered for transplantation in first remission if a related or unrelated donor can be identified. For patients at low risk for relapse (e.g., age 25 or less who have received high-dose intensification), transplantation can be delayed until documentation of early relapse. For patients with Ph1+ ALL or t(4;11), transplantation in first remission should be considered if a suitable related or unrelated donor is identified. Adults with ALL without adverse prognostic characteristics should be considered for transplantation at relapse or in second remission.

Acute Disease↗
PubMed1993

Detection of residual host cells after bone marrow transplantation using non-isotopic in situ hybridization and karyotype analysis.

Karyotype analysis and interphase cytogenetics by means of non-radioactive in situ hybridization (NISH) with Y and X-specific probes were used to detect residual host cells in BM of 18 male patients who had received a BMT from their sisters. All patients but one had a malignant blood disease; 17 patients were clinically in continuous remission at the time of the investigations and throughout the follow-up period. No host cells were detected by karyotype analysis in patients who were in clinical remission. NISH with a biotinylated Y-specific probe showed residual host cells in 16 of the 17 patients in clinical remission. In samples from three patients the existence of host cells was further confirmed by revealing the XY-containing cells with two-color fluorescence in situ hybridization (FISH) using X- and Y-specific probes on direct BM smears showed > 3% residual host cells in 50% of the samples studied at or later than 2 months post-BMT. On conventional cytogenetic preparations < 1% Y-specific cells were detected in all but two samples at > or = 2 months post-BMT. There was no difference in the proportion of host cells between patients conditioned with total body irradiation and CY and those who received busulphan and CY. The recipient's stromal or epithelial cells in the aspirates probably account for most of the host cells detected. In conclusion, small numbers of residual host cells detected by interphase cytogenetics with a Y-specific probe do not indicate an imminent relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Dynamics of erythropoietic recovery following bone marrow transplantation: role of marrow proliferative capacity and erythropoietin production in autologous versus allogeneic transplants.

The mechanisms of erythrocyte recovery after BMT are not known. We investigated the respective role of marrow function and erythropoietin production in 31 ABMT and 47 allogeneic BMT by analysing peripheral counts, serum erythropoietin levels, and serum transferrin receptor (TfR) levels which have been shown to be a quantitative measurement of erythropoiesis. Median times to complete neutrophil (25 vs 48 days, p < 0.0001) and platelet (45 vs 263 days, p < 0.001) recovery were faster after allogeneic BMT than ABMT, but complete erythrocyte recovery was slower (218 vs 101 days, p < 0.001). After ABMT, erythrocyte recovery paralleled that of neutrophils and platelets, and erythropoietin levels remained appropriate for the degree of anemia. After allogeneic BMT, erythrocytes developed independently of the other cell lines and defective erythropoietin production delayed recovery of adequate erythropoietic activity. This correlated with an alteration of renal function only in those patients remaining erythropoietin deficient beyond day 180. However, supranormal erythropoietin levels in interstitial pneumonia suggests that erythropoietin response to hypoxia is not abrogated. CMV infection could also affect erythropoiesis through erythropoietin production after ABMT as well as allogeneic BMT. It is concluded that after ABMT the development of erythropoiesis is determined by the overall marrow proliferative activity and erythropoietin plays only a facilitating role. After allogeneic BMT, erythropoiesis depends on erythropoietin levels which remain inadequate for prolonged periods of time. The results suggest that the administration of recombinant human erythropoietin could reduce transfusion requirements after BMT.

Adolescent↗
PubMed1993

Disseminated subcutaneous Nocardia asteroides abscesses in a patient after bone marrow transplantation.

We describe an unusual case of disseminated subcutaneous abscesses caused by Nocardia asteroides in a 17-year-old female with AML undergoing allogeneic BMT. She was receiving immunosuppressive therapy with CYA and a corticosteroid for acute GVHD, and maintenance therapy with ganciclovir for interstitial pneumonia (IP) caused by CMV, but was not neutropenic. The subcutaneous abscesses spread from the primary infection on her right anterior leg to both thighs, the left buttock, both upper arms, the left forearm and right shoulder, indicating hematogenous dissemination. Nocardia asteroides was identified from biopsy material in culture. The patient was successfully treated with a combination of trimethoprim/sulfamethoxazole (TMP/SMX) and minocycline, given for 3 months. The possibility of nocardiosis should be considered in the differential diagnosis of such patients.

Abscess↗
PubMed1993

Residual clonable host cell detection for predicting engraftment of T cell depleted BMTs.

Rejection of T-depleted BMTs is predominantly mediated by alloreactive host T cells. A low but significant number of radiochemoresistant clonable T cells can be detected following a conventional cytoreductive protocol given prior to T-depleted BMT. Elimination of these cells increases the engraftment rate. We found no clonable T cells at the end of the conditioning regimen in 100 ml of peripheral blood from 47 patients who received an HLA-identical T-depleted BMT. None rejected the graft and none displayed mixed chimerism. In addition, although no clonable T cells were detected in nine patients who received a mismatched BMT, two rejected their graft. However, in three mismatched patients, who for clinical reasons received a modified pre-BMT schedule, the presence of host clonable T cells was associated with immunological rejection. These findings suggest that the detection of clonable T cells should prove a valuable indicator for optimising immunosuppression prior to T-depleted BMT.

Adolescent↗
PubMed1993

Detection by polymerase chain reaction of residual cells with the bcl-2 translocation is associated with increased risk of relapse after autologous bone marrow transplantation for B-cell lymphoma.

Although molecular biologic techniques can now detect minimal numbers of residual cancer cells in patients in complete clinical remission, the clinical significance of minimal residual disease has never been conclusively established. If the detection of minimal residual disease predicts which patients will relapse, then therapy could be altered based upon the detection of these cells. The t(14;18) can be detected by polymerase chain reaction (PCR) amplification in 50% of patients with B-cell non-Hodgkin's lymphoma and allows detection of one lymphoma cell in up to 1 million normal cells. To determine the clinical significance of the detection of minimal residual lymphoma cells in the bone marrow (BM) PCR amplification was used to detect the presence of residual lymphoma cells after autologous BM transplantation (ABMT) in serial BM samples from 134 patients with B-cell lymphoma in whom a bcl-2 translocation could be detected. PCR analysis was performed on a total of 542 BM samples obtained while these patients were in complete remission. Disease-free survival was markedly increased in patients with no PCR-detectable lymphoma cells in the marrow compared with those in whom residual lymphoma cells were detected (P < .00001), and the presence of detectable lymphoma cells was associated with a 48-fold increase in the risk of relapse. Of the 77 patients (57%) with no PCR-detectable lymphoma cells in their most recent BM sample, none have relapsed. In contrast, all 33 patients (25%) who have relapsed had PCR-detectable lymphoma cells detected in their BM before clinical relapse occurred. In 19 patients (14%), residual lymphoma cells in the BM were detected early following transplantation and subsequently were no longer detectable, although these patients received no further therapy. In these patients, residual lymphoma cells may already have been irreversibly damaged by the high-dose therapy or an endogenous immune mechanism may be capable of eliminating residual lymphoma cells in some patients. Therefore, although the detection of minimal residual disease by PCR following ABMT in patients with lymphoma identifies those patients at high risk of relapse, the presence of residual minimal disease early after transplantation may not be associated with poor prognosis in a small subset of patients. Confirmatory studies will be required to determine more definitively the role of minimal disease detection to identify which patients require additional therapy.

Bone Marrow Purging↗
PubMed1993

Adoptive transfer of immunity to hepatitis B virus in mice by bone marrow transplantation from immune donors.

Recipients of allogeneic bone marrow transplantation are immunosuppressed as a result of their primary disease and by myeloablative therapy. Such patients are dependent on multiple blood products and are at risk for hepatitis B virus infection. Active immunization against hepatitis B in the immediate pre- and post-transplant periods is ineffective, presumably because of decreased T cell-dependent B-cell responses. This study was designed to evaluate, in a mouse model system, the transfer of immunity against hepatitis B to bone marrow transplant recipients through immunization of bone marrow donors against hepatitis B before transplantation. Bone marrow donor BALB/c mice were immunized with a recombinant hepatitis B vaccine. Seroconversion to HBs antibody occurred within 4 wk of primary immunization, and antibody levels in treated donor mice rose above 300 mIU/ml after a single booster injection. Bone marrow recipient mice, conditioned by sublethal irradiation, were injected intravenously with bone marrow cells obtained from syngeneic HBs antibody-positive immune donors. Antibody was detected in 10% of bone marrow recipients within 30 days of transplantation and in 56% 1 mo after a booster injection that led to a secondary rise in HBs antibody. Adoptive transfer of immunity to hepatitis B also occurred after transplantation of T cell-depleted bone marrow cells from hepatitis B-immune donors, albeit at a lower HBs antibody level. These results indicate that immunity to hepatitis B can be transferred in mice by bone marrow transplantation from hepatitis B-immune donors to immunosuppressed recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Relevance of marrow fibrosis in bone marrow transplantation: a retrospective analysis of engraftment.

A retrospective study compared posttransplant engraftment parameters in 203 patients with myelofibrosis (MF) with those in a population of 203 matched controls without MF. There were no significant differences between these groups in the proportions of patients who died without achieving engraftment and in the disease-free survival distributions. Furthermore, comparisons between the two groups of patients reaching the respective endpoints showed no differences in the time distributions for reaching 0.5 or 1.0 x 10(9)/L granulocytes, but the time to platelet transfusion independence was 3 days longer in patients with MF. In further analysis, results for 33 patients with severe MF were compared with those of their respective controls. The proportions of patients with severe MF who died without reaching these engraftment endpoints and the disease-free survival distributions in the two groups were similar. Among patients who reached the respective engraftment endpoints, there was no statistically significant difference in the pace of granulocyte recovery. In patients with severe MF, there was a 7-day delay in the time to reach platelet transfusion independence and a 2-day delay in the time to reach red blood cell independence, but the differences were not statistically significant. The present results do not substantiate concerns raised by earlier studies. MF may delay the time to reach platelet independence by approximately 3 days and may increase platelet transfusion requirements, but no other perturbation of hematopoietic reconstitution was apparent.

Adolescent↗
PubMed1995

In vitro sensitivity of post-bone marrow transplantation CFU-GM and BFU-E to TNF-alpha and IFN-gamma.

Graft failure remains one of the limitations of successful marrow transplantation. T cell-depleted (TCD) bone marrow transplantation (BMT) is reported to have a higher incidence of graft failure than unmodified (UM) BMT. In most cases of secondary graft failure, no cellular immune mechanism has been identified and etiology remains unclear. In an effort to delineate a cytokine-mediated mechanism of secondary graft failure, we investigated colony-forming unit-granulocyte/macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-E) growth and pattern of inhibition by tumor necrosis factor-alpha (TNF-alpha) and gamma-interferon (IFN-gamma) in the early posttransplant period (day 28). Gradient-separated bone marrow mononuclear cells (BMMNC) from 38 recipients of TCD BMT, 15 recipients of UM BMT, and 23 normal donors (NLD) were plated in cultures of semisolid, serum-containing medium with the addition of stem cell factor (SCF), erythropoietin (Epo), and granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF). Three to seven times more CFU-GM and BFU-E colonies were cultures from NLD BM-derived BMMNC than from BMMNC of recipients of TCD or UM BMT (p = 0.0001). There was no difference in colony number between recipients of UM and TCD BMT on day 28 posttransplant, however. Under G-CSF culture conditions, CFU-GM colonies from recipients of UM and TCD BMT were more susceptible (p < or = 0.05) to suppression by IFN-gamma at concentrations of 1 and 100 U/mL than NLD BMMNC-derived colonies. No other difference in IFN-gamma inhibition was detected among the three groups. Under G-CSF and GM-CSF culture conditions, maximal inhibition was obtained at TNF-alpha concentrations > 10 ng/mL. Although early posttransplant BMMNC was more sensitive to inhibition than NLD-derived BMMNC, overall, no difference in colony growth or percent of inhibition induced by TNF-alpha or IFN-gamma was observed between recipients of unmodified and T. cell-depleted transplants. In this series, two recipients of TCD BM and one recipient of UM BMT developed graft failure; no distinct pattern of colony growth or colony inhibition was evident for those patients. The optimized in vitro conditions and specific cytokines used in this study do not indicate any quantitative or qualitative differences in the hematopoietic progenitors present in recipients of unmodified and T cell-depleted bone marrow early posttransplant to explain an increased risk of graft failure following a T cell-depleted BMT compared to an unmodified BMT.

Adolescent↗
PubMed1996

Gamma delta T lymphocyte regeneration after T lymphocyte-depleted bone marrow transplantation from mismatched family members or matched unrelated donors.

The recovery of gamma delta T lymphocytes was studied in 31 recipients of T cell-depleted allogeneic bone marrow (BMT) to determine if the dynamics of reconstitution could be related to graft-versus-host disease (GVHD) or other complications of marrow transplantation. Two distinct patterns of regeneration were apparent. In 12 patients, there was a progressive rise in both the percentage and the absolute number of peripheral blood gamma delta T cells over the first year post-transplantation, but these increases never breached levels found in 14 healthy donors. Each of the 19 remaining patients had abnormally high proportions and numbers of gamma delta T cells on at least two occasions following transplantation. The clinical factor that best explained these observations was the frequency of intercurrent infections. Of 19 patients with abnormally increased percentages and numbers of gamma delta T lymphocytes, 18 had one or more episodes of confirmed viral or fungal infection, contrasted with only two of 12 in the comparison group (P < 0.001). There was no significant association of gamma delta T cell recovery patterns with the presence of GVHD (P = 0.33). We conclude that the recovery of gamma delta T lymphocytes after marrow transplantation may vary. Supranormal levels of this T cell subset are associated with infection and may contribute significantly to cellular immune defenses against fungal or viral disease.

Adolescent↗
PubMed1995

Evaluating efficiency of bone marrow harvest and its manipulation--role of CD 34 positivity.

We evaluated harvested marrow cells for total nucleated cells (27.49 x 10(9)), absolute 'lymphocyte' count (6.29 x 10(9)) and CD 34 positive cells (3.57 x 10(9)). The same parameters were studied after in vitro manipulation to remove RBCs and plasma. Reinfused WBCs contained 12.87 x 10(9) nucleated cells, 4.25 x 10(9) absolute 'lymphocyutes' and 3.34 x 10(9) CD 34 positive cells. The corresponding figures for loss during in vitro manipulation (tubing, RBCs and plasma) are 14.62 (53.18%), 2.04 (32.43%) and 0.23 x 10(9) (6.44%) cells respectively. Therefore CD 34 positivity may be a better indicator of total yield, loss during manipulation and reinfusion of hemopoietic progenitor cells in bone marrow transplantation.

Antigens, CD34↗
PubMed1996

The combination of melphalan, cyclophosphamide and cytosine arabinoside as a conditioning regimen for autologous bone marrow transplantation for acute leukemia.

OBJECTIVE: To explore more effective and less toxic conditioning regimen without total body irradiation for autologous bone marrow transplantation (ABMT) for acute leukemia (AL). MATERIAL AND METHODS: Twenty patients with AL were treated with ABMT, including 13 cases of acute myelocytic leukemia (AML) and 7 cases of acute lymphocytic leukemia (ALL). A median of 1.06 (range, 0.69-1.75) x 10(8) nucleated BM cells/kg was harvested and stored in normal salt solution containing heparin at 4 degrees C. The conditioning regimen (MAC) consisted of high-dose melphalan (M, 140-160 mg/m2), cyclophosphamide (CY, 120 mg/kg) and cytosine arabinoside (Ara-C, 2.0 g/m2). These 3 drugs were administered within 25 hours and the unpurged autologous marrow infusion began after another 24-hour interval. RESULTS: MAC regimen could result in myeloblastic efficacy in a week. All marrow cells were reinfused within 56 hours after the harvest so that hemopoietic reconstitutions could occur in all the patients. The median time to reach a neutrophil count of > 1.0 x 10(9)/L and a platelet count of > 50 x 10(9)/L was 20 and 26 days respectively. With a median observation period of 25 months, the median duration on continuous complete remission in our patients was 22 months, and the longest reached 56 months. The median survival was 33 months, and the longest was over 6 years. The event-free survival at 2 years had reached 72%. In seven patients with leukemic relapse, six (86%) relapsed within 8 months after ABMT. The relapse rate and mortality in AML patients were significantly lower than those in ALL patients. In 7 patients with M3, relapse had not yet been observed. The nonhematologic toxic effects of MAC conditioning regimen occurred mainly in the gastrointestinal tract. CONCLUSIONS: The preliminary results indicated that the ABMT using MAC conditioning regimen had some advantages in stronger antileukemic efficacy, less extrahematologic toxicity and earlier recovery of platelet and could greatly prolong the duration of remission and survival in some patients with AL.

Adolescent↗
PubMed1996

Chronic myelogenous leukemia and acute promyelocytic leukemia: new bone marrow transplantation options.

PURPOSE/OBJECTIVES: To describe new bone marrow transplantation (BMT) options for chronic myelogenous leukemia (CML) and acute promyelocytic leukemia (APL), as well as their applications and prognoses, and to describe the role of the oncology nurse in caring for the BMT recipient and options for future nursing research. DATA SOURCES: Published articles, book chapters, and personal experience. DATA SYNTHESIS: Various pretransplant agents and methods are under investigation to improve the outcome and reduce the costs of allogeneic and autologous BMT and peripheral blood progenitor cell (PBPC) transplants. Preliminary results of current studies indicate that autologous BMTs and PBPC transplants have merit as a treatment option in patients with AML and require further research. For patients with APL, BMT usually is reserved for those who fail to achieve or relapse after achieving remission with chemotherapy. Preliminary data show that patients with CML and APL who receive a PBPC transplant engraft more rapidly with decreased morbidity and mortality. CONCLUSIONS: BMT options for patients with CML and APL continue to evolve as advances in pretransplant methods and symptom management become capable of improving the outcome, decreasing costs, and shifting patient care to the outpatient and homecare settings. IMPLICATIONS FOR NURSING PRACTICE: Understanding the marrow transplant options available to patients with CML and APL is essential for nurses. They must stay informed about ongoing improvements in pretransplant processes and symptom-management procedures that reduce BMT morbidity and mortality. Inpatient and outpatient nurses need to collaborate and participate in nursing research to find better ways of providing the best care possible for patients.

Bone Marrow Purging↗