Patients Undergoing Bone Marrow Transplantation Research Articles

Etiology of diarrhea in patients undergoing allogeneic bone marrow transplantation in South India.

No studies so far have examined enteric infections in patients undergoing bone marrow transplantation (BMT) in developing countries where asymptomatic carriage and colonization with enteric pathogens is frequent. A prospective study followed 65 patients who underwent BMT in South India between 1995 and 1998. Patients were screened for enteric pathogens before transplantation, weekly during the first 4 weeks after transplantation, and during all episodes of diarrhea. Enteric pathogens were found in 60% of patients before or after transplantation. Pretransplantation screening revealed asymptomatic excretion of enteric pathogens in 29% (19/65). Forty-eight percent of patients undergoing BMT developed diarrhea. Diarrhea was mainly of noninfectious origin in the first 20 days after transplantation. More than 20 days after transplantation, the major causes of diarrhea were graft-versus-host disease and infection. Parasitic infections other than Cryptosporidium did not contribute significantly to morbidity in the pre- and posttransplantation period. Rotavirus and adenoviruses were found in approximately 12% and 5% of subjects, respectively. Bacterial infections in the posttransplantation period were found to be more common in India than in developed countries. Clostridium difficile-associated diarrhea was seen in the posttransplantation period but not before transplantation. Enterotoxigenic and enterohemorrhagic Escherichia coli caused symptomatic infections in the posttransplantation period, but the association of other classes of diarrheogenic E. coli with diarrhea was doubtful. There was significantly higher mortality (P<0.01) in patients with symptomatic or asymptomatic gastrointestinal infections caused by bacteria than in patients with parasitic or viral infections or without enteric infections.

Fluconazole to prevent yeast infections in bone marrow transplantation patients:: A randomized trial of high versus reduced dose, and determination of the value of maintenance therapy

PurposeTo determine the optimal dose and duration of fluconazole antifungal prophylaxis therapy in bone marrow transplantation patients. Subjects and methodsTwo hundred and fifty-three pediatric and adult bone marrow transplantation patients were randomly assigned to receive fluconazole 400 mg daily (high dose) or 200 mg daily (low dose) while they were neutropenic. After neutrophil recovery, patients were randomly assigned to receive maintenance therapy with either fluconazole (100 mg daily) or clotrimazole troches (10 mg 4 times daily) until 100 days after transplantation. Patients were monitored until 2 weeks after completion of early prophylaxis and to 100 days after transplantation. ResultsDuring the early prophylaxis phase, rates of yeast colonization and infections were similar in both treatment groups. By day 50, the incidence of Candida infections in the high-dose group was 4% (95% confidence interval [CI]: 1% to 7%; n = 5), compared with 1% in the low-dose fluconazole group (95% CI: 0% to 3%; n = 1; P = 0.08). During the same period, the incidence of Aspergillus infections was 4% (95% CI: 1% to 7%; n = 5) in the high-dose group and 2% (95% CI: 0% to 4%; n = 2; P = 0.33) in the low-dose group. During the maintenance prophylaxis phase, rates of yeast colonization and superficial infections were similar in the fluconazole and clotrimazole groups. Four patients developed systemic fungal infection in the maintenance phase (1 who received clotrimazole and 3 who received fluconazole). ConclusionHigh-dose (400 mg daily) and low-dose (200 mg daily) fluconazole have similar efficacy in reducing the incidence of yeast colonization, superficial infection, and systemic infection in neutropenic pediatric and adult patients undergoing bone marrow transplantation. Rates of yeast colonization after neutrophil recovery were similar in patients treated with fluconazole or clotrimazole.

Effect of tolerance to noninherited maternal antigens on the occurrence of graft-versus-host disease after bone marrow transplantation from a parent or an HLA-haploidentical sibling

In haploidentical transplantation, the mismatched haplotype of the donor can originate from either of the parents. We refer to such mismatched haplotypes as noninherited maternal antigens (NIMA haplotype) or noninherited paternal antigens (NIPA haplotype). To determine whether exposure to maternal HLA antigens benefits patients undergoing bone marrow transplantation, we analyzed graft failure and graft-versus-host disease (GVHD) after transplantations from parental or haploidentical sibling donors. We studied 269 patients receiving 1 or 2 HLA-A, -B, -DR antigen-mismatched sibling or parental non-T-cell-depleted bone marrow transplants for acute myelogenous leukemia, acute lymphoblastic leukemia, or chronic myelogenous leukemia between 1985 and 1997 that were reported to the International Bone Marrow Transplant Registry. Included were 121 (45%) NIMA-mismatched and 148 (55%) NIPA-mismatched transplantations. Sixty-three (52%) of the NIMA-mismatched transplants and 69 (47%) of the NIPA-mismatched transplants were from haploidentical sibling donors. Sibling transplantations mismatched for NIMA had similar rates of graft failure but lower rates of acute GVHD (P <.02) than NIPA-mismatched sibling transplantations. In the first 4 months after transplantation, mother-to-child transplantations involved significantly less chronic GVHD than father-to-child transplantations (P <.02). Treatment-related mortality (TRM) was significantly higher after parental transplantations (P =.009 for mother; P =.03 for father) than after haploidentical sibling transplantations mismatched for the NIMA. Non-T-cell-depleted bone marrow transplants donated by haploidentical siblings to recipients mismatched for NIPA and transplants donated by parents caused more acute and chronic GVHD and TRM than transplants donated by haploidentical siblings mismatched for NIMA.

The role of biomedical and psychosocial factors for the prediction of pain and distress in patients undergoing high-dose therapy and BMT/PBSCT.

Recent research has shown that cancer patients undergoing bone marrow transplantation (BMT) experience moderate to severe mouth pain due to treatment-related mucositis in spite of morphine therapy. Treatment-related emotional distress in BMT patients is also described widely. This study examined several biomedical, psychological and social variables as possible predictors for the intensity of treatment-related mouth pain and anxious mood in 63 cancer patients undergoing BMT or stem cell transplantation (SCT) within a prospective longitudinal design. Biomedical predictors included biomedical risk, mucositis, the mode of transplantation, total body irradiation, age and gender. Psychological predictors were depression (BDI), BMT-related distress, chronic stress and resources in everyday life (KISS), pain-related coping behaviour (KPI-17) and social support (ISSS). Among the social variables we evaluated education, being married and the living situation. Criteria variables were the intensity of mouth pain and anxious mood which were assessed daily by numeric self-rating scales for 24 days after transplantation. Results of stepwise multiple regressions indicated that psychological and social variables were important predictors of mouth pain, besides biomedical variables. Whereas the biomedical variables revealed the most predictive power during the second week after BMT, psychological predictors were more important during the early and late phases of the treatment. Daily anxious mood was best predicted by psychological and social variables. Among the biomedical variables mucositis was most strongly related to mouth pain besides mode of transplantation, risk, TBI and age. Among the psychological variables BMT-related distress was the most important predictor, with resources in private life or at work and pain-related coping modes as further significant predictors. These results imply that relevant predictors should be assessed as high risk factors for an increased vulnerability for treatment-related side-effects before treatment starts indicating an additional offer of psychological treatment in high risk patients.

Revisiting the road not taken: integrating palliative care into oncology nursing.

Robert Frost’s poem “The Road Not Taken” presents a metaphor for decision making in life (Lathem, 1969). When one comes to a crossroad, the path he or she chooses has major implications for both the traveler and the path itself. I was reminded of Frost’s work several times in the last few years as I walked an oncology career path focused increasingly on pain and symptom management and quality of life. The more familiar one I had followed to that point—one focused on caring for patients undergoing bone marrow transplant and other investigative anticancer treatments—seemed more distant. Eventually, I realized that in focusing on palliative care, I had made a philosophical shift in my approach to patients. Early on I thought, I’d “keep the first for another day.” But now I realize I could never return to my previous path.

A clinical study on dental management in patients undergoing bone marrow transplantation or peripheral blood stem cell transplantation

A clinical study on dental management in patients undergoing bone marrow transplantation or peripheral blood stem cell transplantation

Circulating IL-8 and IL-10 in euthyroid sick syndromes following bone marrow transplantation.

It is generally agreed that euthyroid sick syndromes (ESS) are associated with an increased production of cytokines. However, there has been scarce data on the relationship thyroid hormone changes and cytokines among the patients undergoing bone marrow transplantation (BMT). Because interleukin-8 (IL-8) has been identified as a potent proinflammatory and interleukin-10 (IL-10) as an antiinflammatory cytokine, we studied the relation between thyroid hormone parameters and these cytokines following BMT. We studied 80 patients undergoing allogeneic BMT. Serum T3 decreased to nadir at post-BMT 3 weeks. Serum T4 was the lowest at the post-BMT 3 months. Serum TSH sharply decreased to nadir at 1 week and gradually recovered. Serum free T4 significantly increased during 3 weeks and then returned to basal level. Mean levels of serum IL-8 significantly increased at 1 week after BMT. Mean levels of serum IL-10 significantly increased until 4 weeks after BMT. No significant correlation was found between serum thyroid hormone parameters and cytokines (IL-8, IL-10) after adjusting steroid doses during the entire study period. In conclusion, ESS developed frequently following allogeneic BMT and cytokine levels were increased in post-BMT patients. However, no significant correlation was found between serum thyroid hormone parameters and these cytokines.

Evaluation of coagulation in pediatric bone marrow transplantation patients

Abstract: A hypercoagulable state is frequently described in adult patients undergoing bone marrow transplantation (BMT). In this study, the coagulation profile of 29 children was prospectively investigated in the pre- and post-transplant period. A significant rise in the activated partial thromboplastin time (aPTT) values was detected on days 7 and 14 after transplantation. Moreover, an increase in the d-dimer level was also notable, regardless of the clinical condition of the patients. The other coagulation parameters investigated (i.e. protein S, protein C, anti-thrombin III, factor VIII, von Willebrand factor, and prothrombin time) remained essentially unchanged. However, hyper-fibrinogenemia was observed in all patients with chronic myeloid leukemia (CML) (n=5) before and after transplantation. In summary, in the present study pediatric bone marrow transplantation patients did not show a hyper-coagulable state after marrow infusion. However, a significant rise in PTT and d-dimer values were noted.

Evaluation of coagulation in pediatric bone marrow transplantation patients

A hypercoagulable state is frequently described in adult patients undergoing bone marrow transplantation (BMT). In this study, the coagulation profile of 29 children was prospectively investigated in the pre- and post-transplant period. A significant rise in the activated partial thromboplastin time (aPTT) values was detected on days 7 and 14 after transplantation. Moreover, an increase in the d-dimer level was also notable, regardless of the clinical condition of the patients. The other coagulation parameters investigated (i.e. protein S, protein C, anti-thrombin III, factor VIII, von Willebrand factor, and prothrombin time) remained essentially unchanged. However, hyper-fibrinogenemia was observed in all patients with chronic myeloid leukemia (CML) (n=5) before and after transplantation. In summary, in the present study pediatric bone marrow transplantation patients did not show a hyper-coagulable state after marrow infusion. However, a significant rise in PTT and d-dimer values were noted.

Quantification of busulfan in plasma by liquid chromatography–ion spray mass spectrometry: Application to pharmacokinetic studies in children

Optimisation of busulfan dosage in patients undergoing bone marrow transplantation is recommended in order to reduce toxic effects associated with high drug exposure. A new method was developed coupling liquid chromatography with mass spectrometry (LC–MS) and was validated for the determination of busulfan concentrations in plasma. Recovery was 86.7%, the limit of detection was 2.5 ng/ml and linearity ranged from 5 to 2500 ng/ml. The correlation between the busulfan concentrations measured by our previously published HPLC–UV method and the new HPLC–MS method was highly significant ( P<0.0001). Sample volume was reduced and the method was rapid, sensitive and less expensive than the methods previously used in our laboratory. This method was used to determine the pharmacokinetic parameters of busulfan after the first administration of 1 mg/kg orally, in 13 children receiving the drug as part of the preparative regimen for bone marrow transplantation. Our results were similar to previously reported data. They showed that the apparent oral clearance of busulfan was 0.299±0.08 l/h/kg, and that it was significantly higher ( P=0.02) in patients below the age of 5 years than in older children.

Off-label use of recombinant factor VIIa in patients following bone marrow transplantation.

Recombinant factor VIIa (rFVIIa, NovoSeven) is FDA-approved for the treatment of bleeding in patients with hemophilia A/B with inhibitors. A growing literature suggests that there may be expanded indications for the use of NovoSeven in patients with significant bleeding who do not have a known factor deficiency. Severe bleeding refractory to standard hematologic or hemostatic support is common in patients undergoing bone marrow transplantation (BMT). We review our experience with rFVIIa in three patients (8 years 8 months to 19 years, median 13 years) treated for pulmonary hemorrhage (n = 1), hemorrhagic cystitis (n = 3), and gastrointestinal bleeding (n = 2). Boluses of 90-270 microg/kg rVIIa with subsequent doses of 90 microg/kg every 4-24 h for 3-14 days were given, concurrent with maintaining platelet counts >50,000/mm(3). Transient clinical responses in gross hematuria (two patients) and in pulmonary hemorrhage were noted within several days of starting rFVIIa, but bleeding in a new site in two patients and renewed bleeding of the initial site in the third resulted in discontinuation of the drug. No toxicity or adverse events were observed while the patients were on rFVIIa treatment. Because of the substantial cost of this product, the lack of adequate monitoring methodology, and the variability of current dose and dosing intervals, large randomized studies are needed before definitive off-label use in the setting of BMT can be recommended.

Autologous peripheral blood stem cell transplant in patients previously diagnosed with invasive aspergillosis.

Patients previously diagnosed with invasive aspergillosis (IA) have been considered to be at risk for relapse of mycosis during subsequent hematopoietic transplant. Even with prophylactic measures, reactivation of the infection occurs in 29% of patients undergoing bone marrow transplantation (BMT). A period of neutropenia is one of the variables considered to be a risk factor for reactivation. Peripheral blood stem cell transplant (PBSCT) results in a shorter neutropenia period leading to a lower risk of fungal infection. A retrospective data analysis performed on patients undergoing autologous PBSCT for hematological malignancies in our unit showed that nine patients were diagnosed before transplantation with IA. All patients received only medical treatment during their primary infection. Medical prophylaxis was administered in seven of these patients, and two underwent transplantation without prophylaxis. All patients developed severe neutropenia after a myeloablative regimen. All but one had neutropenic fever, although the fever was controlled and no fungal complications occurred. All patients in this series achieved complete hematological engraftment without delay in granulocyte recovery (mean: 8.78 vs 9.76; p=0.58). No significant differences were observed in toxicities with regards to transplantation between patients previously diagnosed with IA and their controls. Recurrence of IA related to transplantation was avoided since no relapse of IA was demonstrated. This series of nine patients with a previous history of IA shows that medical treatment, secondary prophylaxis, and peripheral blood as a source of stem cells could be effective measures to avoid reactivation of previous aspergillosis during hematopoietic transplantation, although prospective randomized trials should still be performed to confirm these findings in a wider setting.

Pain language of bone marrow transplantation patients.

Previous studies have shown that hypnosis may be effective in reducing intensity of pain among bone marrow transplantation patients whereas cognitive behavioral intervention without imagery was not effective for this group of patients. Since hypnosis alters patients' perception of pain and cognitive behavioral intervention changes patients' beliefs and improves their coping with pain, we hypothesized that sensory pain is more important than affective pain in understanding the pain experience of patients undergoing bone marrow transplantation. To test this hypothesis we administered the McGill Pain Questionnaire longitudinally to 50 consecutive eligible recipients of bone marrow transplantation during hospitalization to assess the different dimensions of pain they experienced. Consistent with our hypothesis, sensory pain fluctuated with treatment stages, and the pattern was consistent with previous findings. Patients reported significantly higher sensory pain than affective pain at all assessment points. In contrast, affective pain remained low and stable throughout the treatment. Our results contribute to the understanding of the nature of pain in bone marrow transplantation and suggest pain management strategies that focus on sensory pain as in hypnosis are more useful for such patients.

Pharmacogenetics of methotrexate: toxicity among marrow transplantation patients varies with the methylenetetrahydrofolate reductase C677T polymorphism

AbstractThis study investigated whether a polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (C677T) modifies responses to methotrexate (MTX) in patients undergoing bone marrow transplantation. About 10% to 12% of the population carry the MTHFR TT genotype (enzyme activity, 30% of wild type [CC]). Patients (n = 220) with chronic myelogenous leukemia underwent marrow allografts and were given a short course of MTX. MTX toxicity measures included the oral mucositis index (OMI), speed of engraftment (platelet and granulocyte counts), and bilirubin. Patients with lower MTHFR activity (TT genotype) had 36% higher mean OMI during days 1 to 18 (+5.7, P = .046) and 20% higher OMI between days 6 and 12 (+3.8, P = .27). Platelet counts recovered more slowly among patients with the TT genotype compared to wild type (24% slower recovery to 10 000 platelets/μL, P = .23; 34% slower to 20 000/μL, P = .08). Patients with decreased MTHFR activity appear at risk of higher MTX toxicity. Because of the high prevalence of the TT genotype, these results may have implications for MTX dosage.

Gut mucosa barrier preservation by orally administered IgA-IgG to patients undergoing bone marrow transplantation: A randomized pilot study

Gut mucosa barrier preservation by orally administered IgA-IgG to patients undergoing bone marrow transplantation: A randomized pilot study

The hepatologist in the haematologists' camp.

The hepatologist in the haematologists' camp.

Trichosporon species infection in bone marrow transplanted patients

Trichosporon species are emerging as opportunistic agents that cause systemic diseases in immunocompromised patients. Patients undergoing bone marrow transplant are submitted to intense and prolonged periods of neutropenia and consequently to several risk factors to fungal infections as the use of broad spectrum antibiotics and invsive devices. Two cases of fungal infecitons caused by Trichosporon asahii var. asahii and T. inkin in patients with bone marrow transplant are described T. asahii var. asahii was responsible for fungemia and the identification of this microorganism was later performed. T. inkin caused vascular accesses infection and was recovered from an implanted Hickman-Broviac catheter. Both patients were under oral fluconazole prophylaxis. The patient with systemic infection died despite the therapy with amphotericin B and the patient with catheter-related infection recovered from the fungal infection after catheter removal. Difficulties in the identification of this microorganism lead to delays in treatment and post-mortem diagnosis.

Piomiositis en un paciente sometido a trasplante de médula ósea

pruebas: ureasa positiva, crecimiento a 45oC positivo, beta-lactamasa positiva, glucosa y ramnosa positivas, opacificacion del agar Middlebrook, arilsulfatasa negativa y sin descomposicion de los aminoacidos xantina, caseina y tirosina. El microorganismo aislado se identifico finalmente como N. farcinica. Las pruebas de sensibilidad se realizaron mediante el sistema de disco-placa (Mueller-Hinton durante 24 h a 37oC) y concentracion minima inhibitoria (CMI) por el metodo de dilucion en caldo (Sensititre®); la cepa presento resistencia a tobramicina, gentamicina, cefotaxima, cefuroxima, ampicilina, eritromicina, tetraciclina, ciprofloxacino y rifampicina y fue sensible a amikacina, amoxicilina / acido clavulanico, imipenem, sulfamidas y cotrimoxazol. Ante la ausencia de una posible via de entrada cutanea, ya que no se apreciaron heridas o lesiones que lo pudieran justificar, y considerando que pudieran existir focos silentes a otros niveles como pulmon o cerebro, se realizo una tomografia axial computarizada toraco-abdominal y cerebral sin evidenciarse lesiones en estas localizaciones. Se inicio tratamiento antibiotico intravenoso con cotrimoxazol y topico con sulfamidas; a las 48 horas se aprecio una importante mejoria clinica y progresivamente se produjo granulacion del tejido con resolucion completa de la lesion. Durante los controles posteriores el paciente permanecio asintomatico. Seis meses despues el paciente fallecio como consecuencia de una insuficiencia medular.

Is there a graft‐versus‐leukaemia effect in the absence of graft‐versus‐host disease in patients undergoing bone marrow transplantation for acute leukaemia?

During a 13‐year period, 5200 autografts, 1039 HLA‐identical sibling transplants without acute or chronic graft‐vs.‐host disease (GVHD) and 67 twins were reported to the European Group for Blood and Marrow Transplantation EBMT. Follow‐up time was a median of 32 months. Diagnoses were acute myeloid leukaemia (AML, 4521) and acute lymphoblastic leukaemia (ALL, 1785) in first complete remission. The probability of relapse at 5 years was 51 ± 1% in the autografts, 45 ± 8% in the twins and 34 ± 2% among the HLA‐identical siblings (auto vs. sibs, P &lt; 0·0001). In multivariate analyses, the following factors were significantly associated with an increased risk of relapse: ALL vs. AML M3 [relapse rate (RR) 2·29, P &lt; 0·0001], AML non‐M3 vs. AML M3 (RR 1·8, P &lt; 0·0001), autograft vs. sibling transplant (RR 1·76, P &lt; 0·0001), interval diagnosis to transplantation &lt; 261 d (RR 1·45, P &lt; 0·001) and other conditioning vs. total body irradiation (RR 1·16, P = 0·001). Transplant‐related mortality was the same in the three groups at approximately 10% at 2 years. Five‐year leukaemia‐free survival was 42 ± 1% in the autografts, 44 ± 8% in the twins and 58 ± 2% among the siblings (auto vs. sibs, P &lt; 0·0001). The factors significant for relapse were also significant in multivariate analyses for leukaemia‐free survival. In addition, children had a significantly better leukaemia‐free survival than adults (RR 0·82, P &lt; 0·0001). Recipients of bone marrow from HLA‐identical siblings without GVHD had a lower risk of relapse and a better leukaemia‐free survival than recipients of autografts. This may be as a result of a graft‐vs.‐leukaemia effect in the absence of GVHD.

Dermatologic changes associated with roquinimex immunotherapy after autologous bone marrow transplant

Background: Roquinimex (Linomide) is an immunotherapeutic agent used in conjunction with autologous bone marrow transplantation (ABMT) for treatment of acute and chronic myelogenous leukemia (AML and CML). This agent may induce graft-versus-host reactions (GVHR) as well as graft-versus-leukemia (GVL) effects. Objective: We documented the incidence of acute cutaneous GVHR associated with roquinimex immunotherapy. The presence or absence of autologous GVHR was also correlated with a potential GVL effect in patients with CML treated with ABMT and subsequent roquinimex immunotherapy in the period after the transplant. Methods: Fifteen patients undergoing bone marrow transplantation and roquinimex immunotherapy for CML were followed up, and clinicopathologic data were analyzed. Results: Acute cutaneous GVHRs were observed in 6 of 15 patients (40%) treated with roquinimex. Ten of 11 evaluable patients receiving roquinimex exhibited eccrine sweat gland necrosis (ESGN) (90.9%), which was independent of the acute GVHR. Neither bone marrow engraftment status nor the survival rates of patients with and without GVHR was significantly different. Conclusion: Roquinimex immunotherapy enhances the incidence of GVHR and was associated with a high rate of ESGN in patients with CML who were undergoing ABMT. There was no significant association between ESGN and acute GVHR. Acute autologous GVHR caused by roquinimex did not correlate with a GVL effect in our study of 15 patients with CML. (J Am Acad Dermatol 2000;43:437–41.)