Sleep interventions for osteoarthritis and spinal pain: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: To determine if sleep interventions improve pain and sleep in people with osteoarthritis (OA) and/or spinal pain compared to control/placebo. DESIGN: Medline, Embase, AMED, PsycINFO, CENTRAL, CINAHL and PEDro were searched from their inception date to July 2017. Keywords relating to "sleep", "OA", "spinal pain", and "randomized controlled trial (RCT)" were combined. Included RCTs investigated the use of sleep interventions for people with OA and/or spinal pain, and measured at least one sleep and health related outcome. Meta-analyses were performed to pool mean differences for pain and sleep quality. PROSPERO: CRD42016036315. RESULTS: Of 1445 unique records, 24 studies were included. Sixteen studies included participants with spinal pain, seven with OA, and one included a mixed population. Sleep interventions included established sleep interventions (ESI) [cognitive behavioural therapy (CBT) and pharmacological interventions], and a range of others. Intervention periods ranged from 4 to 10 weeks. Thirteen studies were of moderate to high quality (PEDro ≥ 6/10). Due to high heterogeneity between studies we also performed sub-group and sensitivity analyses. ESI decreased Insomnia Severity Index (ISI) for people with low back pain (LBP) (pooled mean difference: -6.78/28, 95% confidence interval (95% CI): [-9.47, -4.09], I2 = 40%) and OA (-2.41, [-4.19, -0.63], 0%). However ESI decreased pain for people with LBP (pooled mean difference: visual analogue scale (VAS) -12.77/100, 95% CI: [-17.57, -7.97], I2 = 0%), but not OA (-2.32, [-7.18, 2.54], 27%). CONCLUSION: ESI appeared to improve sleep and pain for people with LBP, and sleep for people with OA. However more vigorous studies need to be conducted.

Immune response to a thymus-dependent form of B512 dextran requires the presence of Lyb-5+ lymphocytes.

Studies of the ontogeny of the immune response to B512 dextran (Dex) show that antibody responses equal to those of adult mice are not attained until 12 wk of age. We have examined the anti-Dex response after immunization with a thymus-dependent antigen isomaltohexaosyl-keyhole limpet hemocyanin (IM6-KLH) and have shown that the development of the cross-reacting anti-Dex response parallels the development of Lyb-5+ B cells. Adult levels of anti-Dex antibody after immunization with IM6-KLH are achieved in mice between 3 and 12 wk of age, a time when Lyb-5+ cells have reached adult levels. Neonatal mice, immunized at 1 d or 1 wk after birth, failed to produce a significant amount of anti-Dex antibodies, although they did produce IM6-specific antibodies after immunization with IM6-KLH. Data, which support the conclusion from these experiments that Lyb-5+ cells are required for an anti-polysaccharide response even when the immunizing antigen is thymus-dependent, include the failure of IM6-KLH to stimulate a normal anti-Dex response in mice with the xid defect and the direct demonstration in normal adult mice that elimination of Lyb-5+ cells from spleens of mice primed with IM6-KLH abolishes the ability of these cells to transfer an anti-Dex response. The data imply that the expressed B cell repertoire in adult animals is skewed such that the vast majority of B cells capable of responding to polysaccharide determinants are in the Lyb-5+ subset.

Coastal sedimentation across North America doubled in the 20th century despite river dams.

The proliferation of dams since 1950 promoted sediment deposition in reservoirs, which is thought to be starving the coast of sediment and decreasing the resilience of communities to storms and sea-level rise. Diminished river loads measured upstream from the coast, however, should not be assumed to propagate seaward. Here, we show that century-long records of sediment mass accumulation rates (g cm-2 yr-1) and sediment accumulation rates (cm yr-1) more than doubled after 1950 in coastal depocenters around North America. Sediment sources downstream of dams compensate for the river-sediment lost to impoundments. Sediment is accumulating in coastal depocenters at a rate that matches or exceeds relative sea-level rise, apart from rapidly subsiding Texas and Louisiana where water depths are increasing and intertidal areas are disappearing. Assuming no feedbacks, accelerating global sea-level rise will eventually surpass current sediment accumulation rates, underscoring the need for including coastal-sediment management in habitat-restoration projects.

Efficacy of digital cognitive behavioural therapy for symptoms of generalised anxiety disorder: a study protocol for a randomised controlled trial.

BACKGROUND: Generalised anxiety disorder (GAD) is a chronic and disabling condition with considerable personal and economic impact. Cognitive behavioural therapy (CBT) is a recommended psychological therapy for GAD; however, there are substantial barriers to accessing treatment. Digital CBT, in particular smartphone-delivered CBT, has the potential to improve accessibility and increase dissemination of CBT. Despite the emerging evidence of smartphone-based psychological interventions for reducing anxiety, effect size scores are typically smaller than in-person interventions, and there is a lack of research assessing the efficacy of smartphone-delivered digital interventions specifically for GAD. METHODS: In the DeLTA trial (DigitaL Therapy for Anxiety), we plan to conduct a parallel-group superiority randomised controlled trial examining the efficacy of a novel smartphone-based digital CBT intervention for GAD compared to a waitlist control. We aim to recruit 242 adults (aged 18 years or above) with moderate-to-severe symptoms of GAD. This trial will be conducted entirely online and will involve assessments at baseline (week 0; immediately preceding randomisation), mid-intervention (week 3), post-intervention (week 6; primary end point) and follow-up (week 10). The primary objective is to evaluate the efficacy of the intervention on GAD symptom severity compared to a waitlist control at post-intervention. Secondary objectives are to examine between-group effects on GAD at follow-up, and to examine the following secondary outcomes at both post-intervention and follow-up: 1) worry; 2) depressive symptoms; 3) wellbeing; 4) quality of life; and 5) sleep difficulty. DISCUSSION: This trial will report findings on the initial efficacy of a novel digital CBT intervention for GAD. Results have the potential to contribute towards the evidence base for digital CBT for GAD and increase the dissemination of CBT. TRIAL REGISTRATION: ISRCTN, ISRCTN12765810. Registered on 11 January 2019.

Long-term outcomes of adults with acute lymphoblastic leukemia after autologous or unrelated donor bone marrow transplantation: a comparative analysis by the National Marrow Donor Program and Center for International Blood and Marrow Transplant Research.

For adults with high-risk or recurrent ALL who lack a suitable sibling donor, the decision between autologous (Auto) and unrelated donor (URD) hematopoietic stem cell transplantation (HSCT) is difficult due to variable risks of relapse and treatment-related mortality (TRM). We analysed data from two transplant registries to determine outcomes between Auto and URD HSCT for 260 adult ALL patients in first (CR1) or second (CR2) CR. All patients received a myeloablative conditioning regimen. The median follow-up was 77 (range 12-170) months. TRM at 1 year post transplant was significantly higher with URD HSCT; however, there were minimal differences in TRM according to disease status. Relapse was higher with Auto HSCT and was increased in patients transplanted in CR2. Five-year leukemia-free (37 vs 39%) and overall survival (OS) rates (38 vs 39%) were similar for Auto HSCT vs URD HSCT in CR1. There were trends favoring URD HSCT in CR2. The long-term follow-up in this analysis demonstrated that either Auto or URD HSCT could result in long-term leukaemia-free survival and OS for adult ALL patients. The optimal time (CR1 vs CR2) and technique to perform HSCT remains an important clinical question for adult ALL patients.

Phase I-II trial of erythropoietin in the treatment of cisplatin-associated anemia.

BACKGROUND: Cancer patients undergoing chemotherapy with cisplatin-containing regimens often develop anemia. Although the cause is multifactorial, erythropoietin deficiency appears to play an important role. Recombinant human erythropoietin (epoetin) has been reported to be effective in reversing cisplatin-associated anemia in animal studies but not in clinical trials. PURPOSE: This pahse I-II clinical trial was designed to assess the safety and efficacy of treatment with epoetin for anemia associated with cisplatin chemotherapy. METHODS: Twenty-one cancer patients treated with cisplatin and manifesting anemia (hemoglobin level less than 110 g/L) received epoetin at escalating doses (25, 50, 100, or 200 U/kg body weight) intravenously five times a week for 4 weeks. RESULTS: Epoetin was well tolerated, and a maximal tolerated dose was not reached. Two patients experienced hypertension, which responded to standard antihypertensive therapy. No dose-dependent severe toxic effects were seen. The increase in hemoglobin levels from baseline on day 1 of the study was statistically significant after 4 weeks of epoetin therapy in the groups receiving 100 U/kg (mean change +/- SD = 19 +/- 13 g/L; P = .03) or 200 U/kg (mean change = 24 +/- 17 g/L; P = .007). A clinical response--an increase in hemoglobin level greater than 10 g/L--was achieved in 12 patients after 4 weeks of treatment. For these responders, the mean increase in hemoglobin level was 25 +/- 3.3 g/L over the level observed at the same time in the chemotherapy cycle preceding epoetin treatment, and this increase was statistically significant (P = .0001). Neither serum erythropoietin level nor hemoglobin level predicted a patient's response to epoetin. CONCLUSIONS: These preliminary findings suggest that epoetin is effective and well tolerated for the reversal of cisplatin-associated anemia, with the 100-U/kg and 200-U/kg dose levels offering optimal clinical response. IMPLICATIONS: We are conducting a phase III trial to determine the effect of epoetin on transfusion requirements in patients undergoing chemotherapy.

Phase I study of combination drug purging for autologous bone marrow transplantation.

In a phase I clinical trial of autologous bone marrow transplantation, we determined the feasibility of ex vivo purging with high concentrations of pharmacologics in combination. Light-density cells isolated from the grafts of 26 patients with acute leukemia or lymphoblastic lymphoma were treated with 4-hydroperoxycyclophosphamide (4-HC; 30 to 60 micrograms/mL), vincristine (Vcr; 1.5 to 3.0 micrograms/mL), and methylprednisolone sodium succinate (MP; 5 mg/mL). All patients received marrow-lethal induction therapy followed by infusion of the treated grafts. Three patients died of transplant-related complications before achieving peripheral blood recovery of greater than 0.5 x 10(9) granulocytes per liter. All other patients achieved this parameter of engraftment at a median of 35 days after marrow infusion. The median time to last platelet transfusion was 45 days. These durations of aplasia were similar to those experienced by other patients receiving density-gradient separated grafts treated with 60 micrograms/mL of 4-HC as a single agent. No patient required infusion of untreated reserve marrow because of engraftment failure. The colony-forming unit-granulocyte macrophage (CFU-GM) content of the grafts after purging predicted these parameters of engraftment. Colony-forming unit-leukemia (CFU-L) cultured from the grafts of 12 of the patients treated for acute lymphoblastic leukemia (ALL) were considerably more sensitive to the combination regimen than to 4-HC alone; the sensitivity of CFU-GM from these patients did not differ between the two regimens. The results of this trial indicate the feasibility of treating autologous bone marrow grafts with high concentrations of pharmacologics in combination. The use of combinations may increase the efficacy of ex vivo purging without increasing the toxicity to normal hematopoietic cells.

Treatment of chemotherapy-induced anemia with recombinant human erythropoietin in cancer patients.

Thirty patients with chemotherapy-induced anemia were treated with recombinant human erythropoietin for 4 weeks. In this dose-escalation study, cohorts of five to eight patients were treated per dose level. The doses of erythropoietin were 25, 50, 100, 200, or 300 IU/kg/d given intravenously for 5 days each week. Of 30 patients, 15 (50%) had a greater than 10% increase of their hemoglobin (Hb) values and were considered responders. At the two highest dose levels, 11 of 13 patients (85%) responded. In the 15 responding patients, the mean Hb level increased by 1.7 g/dL from baseline compared with an average decrease of 1.5 g/dL in the previous cycles of chemotherapy without erythropoietin administration. Recombinant human erythropoietin is effective in ameliorating chemotherapy-induced anemia when administered in adequate doses.

Association of BK virus with failure of prophylaxis against hemorrhagic cystitis following bone marrow transplantation.

PURPOSE: Hemorrhagic cystitis (HC) after bone marrow transplantation (BMT) has been ascribed to cyclophosphamide metabolites. HC has also been associated with excretion of the BK type of polyomavirus. The relative contributions of cyclophosphamide metabolites and BK virus in the development of HC following BMT are unknown. PATIENTS AND METHODS: We conducted a randomized trial to compare mesna with forced diuresis for prophylaxis against HC in 147 BMT recipients. We studied the association of BK virus with HC in 95 consecutive BMT recipients by prospectively monitoring urinary excretion of BK virus using polymerase chain reaction amplification of viral gene sequences. RESULTS: HC occurred in 37 of 147 (25.2%) transplant recipients. The incidence of HC was similar in patients given mesna (26.8%, 19 of 71) or forced diuresis (23.7%, 18 of 76), and in recipients of allogeneic (27.2%, 18 of 64) or autologous marrow (22.9%, 19 of 83). The incidence of HC was unrelated to primary disease, preparative regimen, or occurrence of graft-versus-host disease (GVHD). Excretion of BK virus was demonstrated in 50 of 95 patients (52.6%); 38 patients (40%) had persistent BK viruria (> or = two consecutive positive samples). HC occurred in 19 of 38 patients (50%) with persistent BK viruria, in one of 12 (8.3%) with only a single urine sample positive for BK virus, and in none of 45 who did not excrete BK virus (P < .0001). Shedding of BK virus also had a strong temporal correlation with onset of HC (r = .95). CONCLUSION: Mesna and forced diuresis are equally effective in abrogating the urothelial toxicity of preparative regimens for BMT. Since HC after BMT is virtually always associated with persistent BK viruria, strategies aimed at the prevention or elimination of viruria in BK seropositive recipients are warranted.

Impact of age on outcome of patients with cancer undergoing autologous bone marrow transplant.

PURPOSE: We examined the impact of age on outcomes in patients with cancer undergoing autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS: All 506 adult patients who underwent ABMT at the Johns Hopkins Oncology Center between January 1987 and January 1994 were studied. A total of 405 patients were aged 18 to 49 years and 101 were aged > or = 50. The effect of age and other prognostic variables on transplant-related mortality (TRM), relapse, and event-free survival rates were analyzed. RESULTS: Patients aged > or = 50 years has a 2.24-fold increased risk of TRM. Although relapse rates were not different based on age, the increased TRM rate resulted in a slight decrease in overall event-free survival in the older patients. Causes of death were not different by age and were mainly related to preparative regimen toxicity. Length of hospital stay and hospitalization costs were not increased in the older patients. CONCLUSION: While the TRM rate was higher in older patients, relapse rates were not increased. Nearly 25% of older patients were expected to be cured of the disease. These data support the use of ABMT in eligible older patients, at least up to the age of 65.

Autotransplants for Hodgkin's disease in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry.

PURPOSE: Hodgkin's disease patients who never achieve complete remission with conventional chemotherapy (i.e., those with primary induction failure) have a poor prognosis. Some subjects who receive high-dose therapy with autologous hematopoietic progenitor-cell infusion experience prolonged progression-free survival. PATIENTS AND METHODS: Detailed records from the Autologous Blood and Marrow Transplant Registry (ABMTR) on 122 Hodgkin's disease patients who failed to achieve complete remission after one or more conventional therapy regimens and subsequently received an autotransplant between 1989 and 1995 were reviewed. RESULTS: Median age was 27 years (range, 7 to 57 years). Median time from diagnosis to transplantation was 14 months (range, 5 to 38 months). Most patients received high-dose chemotherapy without radiation for pretransplantation conditioning (n = 107). The regimen most frequently used was cyclophosphamide, carmustine, and etoposide (n = 47). Fifteen patients received total-body irradiation (n = 15). The graft consisted of bone marrow (n = 86), blood stem cells (n = 25), or both (n = 11). The 100-day mortality was 12% (95% confidence interval, 7% to 19%). Sixty patients (50%) were considered to have achieved complete remission after autotransplantation; 37 of these had negative imaging studies, whereas scan abnormalities of unknown significance persisted in 23 patients. Twenty-seven patients (22%) had no response or progressive disease after transplantation. Probabilities of progression-free and overall survival at 3 years were 38% (95% confidence interval, 28% to 48%) and 50% (95% confidence interval, 39% to 60%), respectively. In multivariate analysis, "B" symptoms at diagnosis and poor performance score at transplantation were adverse prognostic factors for outcome. CONCLUSION: Autotransplants should be considered for patients with Hodgkin's disease who do not achieve complete remission with conventional therapy.

Long-term results of blood and marrow transplantation for Hodgkin's lymphoma.

PURPOSE: To evaluate the long-term outcome after allogeneic (allo) and autologous (auto) blood or marrow transplantation (BMT) in patients with relapsed or refractory Hodgkin's lymphoma (HL). PATIENTS AND METHODS: We analyzed the outcome of 157 consecutive patients with relapsed or refractory HL, who underwent BMT between March 1985 and April 1998. Patients

A phase II "window" study of topotecan in untreated patients with high risk adult acute lymphoblastic leukemia.

To further evaluate the activity of topotecan (TPT) in acute leukemia, TPT was administered (2.1 mg/m2/day for 5 days by continuous i.v. infusion) to adult patients with previously untreated acute lymphoblastic leukemia (ALL) with high-risk features (13 patients) or relapsed ALL (1 patient). Patients achieving a partial response or significant hematological improvement received a second course. All patients subsequently received standard treatment for ALL. Because complete response was achieved in only 1 of 14 patients, the study was terminated prematurely. An additional patient achieved minimal response, and a third patient normalized her hemogram despite ongoing leukemia in the marrow. Overall, six patients had significant hematological improvement (normalization of platelet and/or absolute neutrophil count). Two patients expired due to infections during induction chemotherapy. The primary nonhematological toxicities were mucositis and diarrhea. Exposure to TPT did not appear to influence the response to subsequent standard chemotherapy. The mean steady-state TPT plasma concentration, 16.1+/-1 nM, overlapped the range of LD90 values of primary human leukemia specimens. Cellular topo I content varied over a 3-fold range, encompassing levels found previously in relapsed patients. No relationship was found between topo I expression and markers of cellular proliferation or response to therapy. In contrast, low expression of the apoptosis inhibitor Bcl-2 was associated with response to TPT therapy. TPT has significant, albeit modest, single-agent activity against high-risk adult ALL. This study demonstrates the feasibility of evaluating promising new therapeutic agents in untreated patients with acute leukemia at high risk for failure with conventional therapy.

A phase I and pharmacological study of topotecan infused over 30 minutes for five days in patients with refractory acute leukemia.

The principal objectives of this study were to determine the feasibility of escalating doses of the hydrophilic topoisomerase I (topo I) inhibitor topotecan (TPT) as a 30-min infusion daily for 5 days in adults with refractory or relapsed acute leukemia and to study the pharmacokinetic behavior of high doses of TPT and pharmacodynamic determinants of TPT activity. Fourteen patients received 27 courses of TPT at doses ranging from 3.5 to 5.75 mg/m2/day every 3 weeks. A constellation of unusual adverse effects, consisting of high fever, rigors, precipitous anemia, and hyperbilirubinemia, was the principal dose-limiting toxicity of high doses of TPT on this schedule. These toxicities were consistently intolerable at the 5.75 mg/m2/day dose level; however, they were neither severe nor common at lower doses. Although the precise etiology of these effects is not known, high doses of TPT may induce acute hemolytic reactions in this patient population. Severe, albeit transient, mucositis was experienced by two of eight patients in 2 of 17 courses at the next lower dose level, 4.5 mg/m2/day, which was determined to be the maximum tolerated dose and the dose recommended for further trials. The pharmacokinetic behavior of TPT at high doses was not dose dependent and resembled that at lower doses. In view of preclinical data suggesting that TPT sensitivity might correlate with topo I levels, topo I content in leukemia blasts was assessed by Western blotting. Variations in topo I content were observed. Moreover, strong correlations were evident between topo I content and two markers of proliferation, proliferating cell nuclear antigen and nuclear protein B23, raising the possibility that differences in topo I content observed among various leukemia specimens might reflect differences in the proliferating fractions of cells in various leukemia samples. Although complete clearance of circulating leukemia blasts occurred in most courses, neither sustained responses nor hematopoietic recovery were observed in the heavily pretreated, poor-risk patients enrolled in this study, and it was not possible to correlate these differences in topo I content with clinical response. These results indicate that substantial dose escalation of TPT as a 30-minute infusion for a 5-day schedule above myelosuppressive doses is feasible in adults with refractory or relapsed leukemias; however, further development of alternate high-dose schedules in leukemia may be warranted in view of the nature of the dose-limiting toxicity and the lack of sustained clinical responses in this preliminary investigation.

Impact of the putative differentiating agent sodium phenylbutyrate on myelodysplastic syndromes and acute myeloid leukemia.

Sodium phenylbutyrate (PB) is an aromatic fatty acid with cytostatic and differentiating activity against malignant myeloid cells (ID(50), 1-2 mM). Higher doses induce apoptosis. Patients with myelodysplasia (n = 11) and acute myeloid leukemia (n = 16) were treated with PB as a 7-day continuous infusion repeated every 28 days in a Phase I dose escalation study. The maximum tolerated dose was 375 mg/kg/day; higher doses led to dose-limiting reversible neurocortical toxicity. At the maximum tolerated dose, PB was extremely well tolerated, with no significant toxicities; median steady-state plasma concentration at this dose was 0.29 +/- 0.16 mM. Although no patients achieved complete or partial remission, four patients achieved hematological improvement (neutrophils in three, platelet transfusion-independence in one). Other patients developed transient increases in neutrophils or platelets and decrements in circulating blasts. Monitoring of the percentage of clonal cells using centromere fluorescence in situ hybridization over the course of PB administration showed that hematopoiesis remained clonal. Hematological response was often associated with increases in both colony-forming units-granulocyte-macrophage and leukemic colony-forming units. PB administration was also associated with increases in fetal erythrocytes. These data document the safety of continuous infusion PB and provide preliminary evidence of clinical activity in patients with myeloid malignancies.

The effect of graft purging with 4-hydroperoxycyclophosphamide in autologous bone marrow transplantation for acute myelogenous leukemia.

BACKGROUND: Autologous bone marrow transplantation is an important therapy for patients with acute myelogenous leukemia (AML). However, leukemia in the graft may contribute to posttransplant relapse. Treatment of the graft with 4-hydroperoxycyclophosphamide (4HC) is sometimes used to decrease numbers of infused leukemia cells (4HC purging). No large controlled trials evaluating efficacy and toxicity of 4HC purging are reported. METHODS: We studied 294 patients reported to the Autologous Blood and Marrow Registry receiving either a 4HC-purged (n = 211) or unpurged (n = 83) autograft for AML in first (n = 209) or second (n = 85) remission. Analyses were restricted to patients transplanted less than 6 months after achieving remission. Using Cox proportional hazards regression, we compared time to treatment failure (death or relapse, inverse of leukemia-free survival) after 4HC-purged vs unpurged transplants while controlling for important prognostic factors. RESULTS: Median duration of posttransplant neutropenia was 40 (range, 10-200) days after 4HC-purged transplants and 29 (9-97) days after unpurged transplants (p < 0.01). Transplant-related mortality was similar in the two groups. In multivariate analysis, patients receiving 4HC-purged transplants had lower risks of treatment failure than those receiving unpurged transplants (relative risk, 0.69, p = 0.12 in the first posttransplant year; relative risk, 0.28, p < 0.0001 thereafter). Adjusted three-year probabilities of leukemia-free survival (95% confidence interval) were 56% (47-64%) and 31% (18-45%) after 4HC-purged and unpurged transplants in first remission, respectively. Corresponding probabilities in second remission were 39% (25-53%) and 10% (1-29%). CONCLUSION: Grafts purged with 4HC are associated with higher leukemia-free survival after autologous bone marrow transplants for AML.

Long-term follow-up of intensive ara-C-based chemotherapy followed by bone marrow transplantation for adult acute lymphoblastic leukemia: impact of induction Ara-C dose and post-remission therapy.

We report single institution outcome of brief, intensive ara-C-based chemotherapy using bone marrow transplantation as primary intensification for untreated adult patients with acute lymphoblastic leukemia (ALL). Overall disease-free and overall survival were inferior to those reported with prolonged chemotherapy modeled on pediatric protocols. Survival and disease-free survival were superior for patients receiving allogeneic BMT compared with chemopurged autologous transplant or maintenance chemotherapy (patients ineligible for or declining BMT). In multivariate analysis, non-L2-FAB, higher ara-C dose, absence of CNS disease, non-Ph1+ karyotype, allogeneic BMT, T cell phenotype, and younger age were associated with improved disease-free survival. Autologous BMT was not superior to chemotherapy, and appears unlikely to provide adequate curative treatment for most adult ALL patients if not followed by maintenance.

Erythropoietin in stem cell transplantation.

Anemia is universal after allogeneic and autologous stem cell transplantation, with both increased red cell utilization and decreased production playing a role. This anemia sometimes is associated with a relative erythropoietin deficiency. In allogeneic stem cell transplantation, randomized trials have demonstrated improved erythropoiesis and a decrease in red cell transfusions in recombinant human erythropoietin (rHuEPO)-treated patients. Studies of rHuEPO in patients undergoing autologous stem cell transplants, however, have not shown a benefit. The role of rHuEPO in stem cell mobilization and treatment of delayed erythropoiesis has yet to be defined and further studies are needed.

Utility of fiberoptic bronchoscopy in bone marrow transplant patients.

Fiberoptic bronchoscopy (FOB) has been reported to have a high diagnostic yield and to be safe in BMT patients with pulmonary infiltrates. At our institution, BMT patients with respiratory symptoms and/or pulmonary infiltrates had a thoracic CT and bronchoalveolar lavage (BAL). Transbronchial biopsy (TBBx) was considered if the platelet count could be raised to >30 x 10(9)/l. From March 1993 to August 1995, 52 patients had 68 FOBs (42 BAL + TBBx, 26 BAL only) for 60 episodes of clinical pneumonia. Patients' characteristics were: 38 males, mean age 42 years, and 39 allogeneic BMTs. Of the 68 FOBs, 47 were performed to evaluate diffuse infiltrates, 10 were done on mechanically ventilated patients, and 50 of the FOBs were preceded by a platelet transfusion. Thirty-one percent of FOBs (21 FOBs, 19 patients) were diagnostic. Twenty-four percent of FOBs (11 diagnostic FOBs, six nondiagnostic FOBs) changed therapy. Ten complications (15%) occurred in 10 FOBs (five acute respiratory failure, three pneumothoraces, one nose bleed, one death). Hospital and 6-month survival based on episodes of clinical pneumonia were 47 and 32%, respectively. Patients who had a diagnostic FOB or a FOB that changed treatment did not have better hospital or 6-month survival compared to patients who had FOBs that were nondiagnostic or did not change treatment. FOB in our BMT patient population, had a low diagnostic yield (31%), infrequently changed treatment (24%), a significant complication rate (15%) and was not associated with improved patient survival. The role of routine diagnostic FOB in BMT patients with pulmonary infiltrates and/or respiratory symptoms should be reevaluated.