Fludarabine, cytarabine, and G-CSF (FLAG) for the treatment of acute myeloid leukemia relapsing after autologous stem cell transplantation

 Twenty-six patients affected by acute myeloid leukemia (AML) who relapsed after autologous stem cell transplantation (ASCT) were treated with the FLAG regimen (fludarabine, cytarabine, and G-CSF). Their median age was 39 years (range 14–59). The median interval from achievement of CR to ASCT was 4 months (2–8). The conditioning regimen was BAVC (BCNU, amsacrine, VP-16, cytarabine) in eight patients, BuCy (busulfan, cyclophosphamide) in 13, and TBI-Cy (total body irradiation, cyclophosphamide) in five. Relapse occurred after a median of 7 months (2–18). ASCT had been performed in CR1 for 23 patients and in CR2 for three. Nineteen patients had been given bone marrow, seven peripheral blood stem cells collected following consolidation plus G-CSF. Overall, CR was obtained by 13 patients (50%), all remitters requiring a single course. The median time for hematological recovery of neutrophils >500/μl and platelets >20,000/μl was 24 and 30 days, respectively. The median duration of G-CSF administration was 25 days, while the median hospitalization was 31 days. There were four deaths in induction (15%), while nine patients (35%) were resistant. After achieving CR, two patients received allogeneic BMT, five a second ASCT, and four were consolidated with HD-ARA-C. Only two patients were judged unable to receive any further therapy. There were 14 documented infections, while nine patients experienced fever of unknown origin. WHO >2 nonhematological toxicity consisted of stomatitis (50%), hepatic dysfunction (11%), diarrhea (11%), and lethargy (4%). Median overall survival and disease-free survival were 6 and 13 months, respectively. Six patients are in CCR at present. We conclude that FLAG is effective in patients with AML who are relapsing after ASCT. The toxicity is acceptable, enabling most patients to receive further treatment, including second transplantation procedures. Received: October 19, 1998 / Accepted: March 30, 1999     

The role of infections in primary hemophagocytic lymphohistiocytosis: a case series and review of the literature.

There is a paucity of literature addressing infection-related morbidity and mortality in children with primary hemophagocytic lymphohistiocytosis (HLH), a rare condition characterized by abnormal proliferation of macrophages, hypercytokinemia, and T cell immunosuppression. Therefore, a retrospective chart review was done of patients diagnosed with primary HLH over a 15-year period. Significant infections present at diagnosis, during the course of illness, and just prior to death or at autopsy were noted. Of the 18 children identified with primary HLH, an infectious agent was documented at the initial presentation of HLH in 5. Significant infections occurred during therapy in 10 (56%) of 18. Of the 12 fatal cases, invasive infection was the cause of death in 8 children, and 6 of these deaths were directly attributable to invasive fungal infection. Significant infections were common during therapy in children with primary HLH, and fungal infections were an important cause of mortality in this group.     

Second autologous transplant as salvage therapy in multiple myeloma

High‐dose chemotherapy followed by autologous haematopoetic stem cell transplantation (ASCT) is a standard frontline therapy for multiple myeloma (MM). Unfortunately, there are no randomized clinical studies examining the role of a second ASCT in patients who relapse after the initial autotransplant. Analysing all available retrospective studies, it seems that salvage ASCT can safely be performed in most patients with an overall treatment‐related mortality rate <5%. Approximately 65% of patients will achieve an objective response and progression‐free and overall survival will be around 12 months and 32 months, respectively. Retrospective data suggest that patients with a progression‐free survival of ≥18 months after initial ASCT are most likely to benefit from a salvage autotransplant. However, patients with a <12‐month duration of response after initial ASCT should not be considered for a second autograft in the relapsed setting because this group will probably only experience ASCT‐related toxicity without any clinical benefit. Quality of response after initial ASCT and number of therapies preceding salvage ASCT may also have a predictive value. Importantly, these findings need to be verified by randomized clinical trials in order to firmly integrate salvage ASCT into a global therapeutic concept for myeloma patients including optimized induction, consolidation, and maintenance approaches.     

Soft tissue infections in children: a retrospective analysis of 242 hospitalized patients

Pediatric soft tissue infections (STIs) are frequently seen disorders that represent one of the most common indications for antimicrobial therapy. We conducted a retrospective analysis of 242 patients who were hospitalized with STIs during the period from January 2000 to January 2004. The ages of the patients ranged from 1 month to 180 months (mean 44.33 +/- 36.92 months). The STIs were distributed as cellulitis in 96 (39.7%) patients, cervical lymphadenitis in 62 (25.6%), cervical abscess in 49 (20.2%), subcutaneous abscess in 25 (10.3%), pyomyositis in 6 (2.5%) and necrotizing fasciitis in 4 (1.6%). In 103 (42.2%) patients, a predisposing factor was found. Blood cultures yielded positive results in 18 (7.4%) cases. The responsible microorganisms were identified in 74 (30.6%) patients. The initial therapy consisted of ampicillin/sulbactam in 166 (68.6%) patients, ceftriaxone or cefotaxime in 58 (24.0%), and ceftriaxone plus clindamycin in 18 (7.4%). Surgical drainage was performed in 65 (86.7%) patients with abscesses. White blood cell count, C-reactive protein, and erythrocyte sedimentation rate returned to normal in mean periods of 3, 7 and 10 days, respectively. The mean duration of parenteral antibiotic therapy was 10 days, and the duration of treatment was found to increase with increasing C-reactive protein and erythrocyte sedimentation rate on admission (P = 0.001 and P < 0.001). Complications developed in 12 (4.8%) patients; there was no mortality.     

Extracorporeal photopheresis therapy in the management of steroid-refractory or steroid-dependent cutaneous chronic graft-versus-host disease after allogeneic stem cell transplantation: feasibility and results

We conducted a retrospective analysis of all allogeneic stem cell transplantation (ASCT) patients started on extracorporeal photopheresis (ECP) for the management of steroid-dependent (SD) or steroid-refractory (SR) cutaneous chronic graft-versus-host disease (cGVHD) following ASCT during a 36-month period (9/98-8/01). Only SD or SR patients who were treated by ECP after day 100 and who received at least 4 weeks of ECP were considered evaluable for this analysis. Out of 64 ASCT patients reviewed, 32 patients met the inclusion criteria. All 32 patients had been previously treated with systemic corticosteroids with 11 (34%) being SR and 21 (66%) SD. Cutaneous cGVHD was extensive in 28 patients (88%) and was accompanied by visceral (hepatic, gastrointestinal) cGVHD in 23 patients (72%). The 32 evaluated patients had received a median of three prior therapies before ECP, most commonly systemic corticosteroids, tacrolimus, and mycophenolate mofetil. Patients received a median of 36 ECP sessions (range 12-98) over a median of 5.3 months (range 1-28), with a median of six sessions per month. The complete response (CR) rate was 22% (n=7) and the partial response rate was 34% (n=11). In all, 28 patients were on systemic corticosteroid therapy at ECP initiation and 18 patients achieved 50% dose reduction while on ECP, yielding a 64% steroid-sparing response rate. Of seven CRs, five are ongoing. A total of 11 (34%) patients have died after ECP, with all cases due to visceral cGVHD or cGVHD-related infectious complications. All 21 surviving patients remain on at least some immunosuppressive cGVHD therapy (including ECP in eight). Overall, ECP displays a substantial response rate and, in particular, steroid-sparing activity in SR/SD extensive cutaneous cGVHD. However, most patients continue to require at least some chronic therapy and cGVHD-related morbidity and mortality remain high.     

Late non-relapse mortality among adult autologous stem cell transplant recipients: a nation-wide analysis of 1,482 patients transplanted in 1990-2003

Data on the incidence and causes of late (>100 d) non-relapse mortality (NRM) in autologous stem cell transplant (ASCT) recipients is limited. We have analysed NRM in a cohort of 1,482 adult patients who received ASCT in 1990-2003 in six Finnish transplant centres. The most common diagnoses included non-Hodgkin's lymphoma (NHL) (n = 542), multiple myeloma (MM) (n = 528), breast cancer (n = 132); Hodgkin's lymphoma (HL) (n = 86) and chronic lymphocytic leukaemia (CLL) (n = 63). Until September 2005, 646 patients (44%) have died. Late NRM was observed in 68 patients (4.6% of ASCT recipients; 11% of all deaths). There were 38 males and 30 females with a median age of 58 yr (20-69) at the time of ASCT. The median time to NRM was 27 months from ASCT (3-112). The risk of NRM was highest in patients with CLL (9.5%) and those with HL (8.1%) followed by MM and NHL (4.9% and 4.8%, respectively). The risk of late NRM was comparable in patients who received total body irradiation (TBI) and those who received chemotherapy-only regimens (6.7% vs. 4.3%). Another malignancy was the most common cause of late NRM (24 patients, 35% of late NRM). Twelve patients (0.8% of ASCT recipients) have died due to secondary haematological malignancy. Altogether 22 patients (32% of late NRM) died from infectious causes. Malignancies and late infections are important causes of NRM after ASCT. These facts point out the importance of prolonged follow-up in ASCT recipients.     

多发性骨髓瘤患者自体造血干细胞移植后感染的临床特征

目的 了解多发性骨髓瘤(MM)自体造血干细胞移植(ASCT)后感染的临床特点.方法 回顾性分析在中山大学附属第一医院住院诊治并接受ASCT治疗的37例MM患者,记录移植后6个月内的感染类型、时间、病原体以及疗效和转归.结果 在ASCT后6个月内有33例(89.2%)患者在观察期间出现59例次感染,其中30例患者在观察期间出现34例次(57.6%)细菌感染,12例患者在观察期间出现15例次(25.4%)真菌感染.既往曾合并真菌感染患者在移植后发生真菌感染比例高于没有合并真菌感染的患者(P=0.040).观察期间分别出现4例(6.8%)巨细胞病毒(CMV)、3例(5.1%)带状疱疹病毒感染及3例(5.1%)HBV再激活.移植后早期感染中细菌感染占62.8%,真菌感染28.6%,病毒感染8.6%,其中病毒感染均为CMV感染,移植后早期未见水痘带状疱疹病毒和HBV感染.移植后中期感染中细菌感染占50.0%、真菌感染20.8%、病毒感染29.3%,移植后早期与中期感染比例差异无统计学意义(P=0.106).38例次(64.4%)感染在应用首选抗感染治疗即得到控制.3例(8.1%)由于感染相关死亡.结论 MM患者ASCT后感染发生率高,各种病原体均易感,需要尽早合理抗感染治疗,降低感染相关病死率.

Abstract：

Objective To explore the clinical features of infection in multiple myeloma (MM)undergoing autologous hematopoietic stem cell transplantation (ASCT). Methods Thirty-seven patients with MM undergoing ASCT were retrospectively analyzed for type and time of infection, pathogen, and outcome. Results Fifty-nine cases of infectious complications occurred in 33 patients (89. 2% ) after ASCT, with 34 cases (57.6%) of bacterial infections in 30 patients, 15 cases (25.4%) of fungal infections in 12 patients, 4 cases (6. 8% ) of cytomegalovirus (CMV) infection, 3 cases (5. 1% ) of herpes zoster virus infection and 3 cases (5. 1% ) of HBV reactivation. The proportion of bacterial infection, fungal infection and virus infection were 62. 8%, 28.6% and 8. 6% respectively in the early stage after ASCT, and 50. 0%, 20. 8% and 29. 3% respectively in the median stage. Response to first-line antibiotic therapy was seen in 38 cases (64. 4% ). Infection-related mortality was 8. 1% (3 cases). Conclusions The incidence of infection in MM patients undergoing ASCT is high and they are susceptible to all pathogens. It is important to choose the right antifungal agents as quickly as possible to reduce infection-related mortality.     

The non-relapse mortality rate for patients with diffuse large B-cell lymphoma is greater than relapse mortality 8 years after autologous stem cell transplantation and is significantly higher than mortality rates of population controls

High dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the preferred treatment modality for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). To assess long-term outcomes of these patients, we retrospectively analysed data from 309 consecutive patients who underwent ASCT for DLBCL between 1994 and 2006. We found that non-relapse mortality (NRM) became the major cause of death beginning approximately 8 years after ASCT. The most common causes of NRM during the study period were respiratory failure (31%), infection (13%), cardiac toxicity (15%) and secondary malignancy (15%). The strongest predictor of relapse mortality (RM) was disease status at transplant: patients who were in second or greater complete or partial remission had a higher risk of RM than those in first complete or partial remission [hazard ratio (HR) 3·7, P<0·001], as did those who were relapsed or refractory (HR 4·9, P<0·001). We describe the longest reported follow-up of a large cohort of DLBCL patients uniformly-treated with ASCT. Although relapse was initially the more likely cause of death, NRM exceeded RM after 8 years. After ASCT, surviving patients have significantly increased risk mortality rates relative to the general population and this excess risk persists over time.     

Low mortality among patients with spinal cord injury and bacteremia

We reviewed 103 episodes of bacteremia in 93 patients with spinal cord injury who had bacteremia during initial hospitalization (39 patients) or readmission (54 patients) during 1978-1988. Eighteen episodes (18%) were due to polymicrobial infections. Urinary tract infections (47%), infected pressure areas (19%), and pneumonia (9%) were the most frequent primary infections and sources of the bacteremia. The bacteria most frequently associated with urinary tract infections were enterococci (26%), Escherichia coli (26%), Pseudomonas species (20%), and Klebsiella pneumoniae (12%). Bacteria most frequently isolated from patients with infected pressure areas were anaerobes and Staphylococcus aureus. Bacteremia was the cause of death for 8 patients (9%). The urinary tract was identified only once as the source of gram-negative bacteremia in an immunocompetent patient who died. The reason for the low mortality in patients with spinal cord injury is unclear.     

Combination of Amikacin and either Ampicillin or Cephalotin as Initial Treatment of Febrile Neutropenic Patients

ABSTRACT. A prospective, randomized trial of two antibiotic combinations (amikacin plus either ampicillin or cephalotin) was performed on 39 consecutive episodes of fever in 30 patients with neutropenia and hematological malignancy. Infections were documented as the cause of fever in 37 episodes (95%): in 21 episodes (54%) bacteria or a virus (n=1) were isolated, and in 16 (41% of all episodes) the infection was documented clinically but no pathogen was isolated. The most frequently isolated bacteria were Staph, aureus (38% of all strains), E. coli (13%), and Pseudomonas aeruginosa (13%). Bacteremia occurred in 18% of the febrile episodes. Improvement followed treatment with the combination amikacin plus ampicllin in 73% of 19 cases, and with amikacin plus cephalotin in 55% of 20 cases (p>0.05), giving a total Improvement rate of 64%. Failure of therapy was seen in episodes caused by multiple bacteria or Pseudomonas infections. Mild signs of nephrotoxicity were noted in 13% during both regimens. Audiograms were normal in all but two patients who showed slight high-frequency hearing loss. A second infection occurred in 7 episodes (18%). Thus, the combination of amikacin plus ampidllin was as efficient (but less expensive) as amikacin plus cephalotin in the initial treatment of febrile episodes in neutropenic patients with hematological malignancies.     

Ceftazidime as initial therapy in febrile patients with acute leukemia during induction chemotherapy. Leukemia Group of Middle Sweden.

We studied the efficacy of ceftazidime as initial monotherapy in 82 adult patients with acute leukemia who developed 123 febrile episodes during induction chemotherapy. 88% of the patients survived their febrile episode(s), whereas 10% died of infection. When assessed at 72 h after initiation of treatment (early evaluation), 43/123 episodes (35%) had been successfully treated with ceftazidime. These 43 favourable responses were seen in 15/47 (32%) microbiologically documented infections, 20/46 (43%) clinically defined infections, and 8/30 (27%) fever of unknown origin (FUO). At the resolution of fever (late evaluation) 115 episodes were evaluable, and 48% had responded successfully to ceftazidime. Successful treatment was most frequently observed in FUO, 18/29 (62%). In contrast, only 19/44 (43%) microbiologically documented infections and 18/42 (43%) clinically defined infections were cured during ceftazidime treatment. In bacteremia the response rate was only 8/26 (31%). Thus, this study shows that although ceftazidime can be safely used for initial empirical monotherapy in neutropenic leukemia patients, the need for therapy modification is high and few patients with serious infections are cured with ceftazidime alone.     

Acute epiglottitis in adults

We treated four adults whose upper airway was compromised due to acute epiglottitis. We also reviewed the English literature for all reports of this condition in adults (18 years and older). Among the 158 cases, the infectious etiology was identified in 29 (H. influenzae 20, Streptococcus pneumoniae six, H. parainfluenzae two, Streptococcus pyogenes one). In the remaining cases, the etiology was uncertain. Bacteremia was documented in 23/32 patients (71.9%), but extra-epiglottic infections were strikingly rare (X = six). The clinical manifestations were sore throat (100%), fever (88%), dyspnea (78%), dysphagia (76%), anterior neck cellulitis or tenderness (27%), hoarseness (21%), pharyngitis (20%) and anterior cervical lymphadenopathy (9%). Complete airway obstruction ensued in 23 out of the 119 subjects (18.3%) who had respiratory difficulty. Overall mortality rate was 17.6% but it was 6.4% among the patients who were semi-electively tracheostomized or endotracheally intubated. These findings illustrate that antibiotics therapy active against H. influenzae is required in the treatment of acute epiglottitis in adults. Additionally, airway patency should be established when inspiratory stridor appears assuring uncomplicated recovery.     

Evaluation of infectious etiology and prognostic risk factors of febrile episodes in neutropenic cancer patients

OBJECTIVES: Febrile neutropenic cancer patients are at risk for development of serious infections, morbidity and mortality. The aim of this study was to determine the type and frequency of infections and to evaluate some prognostic risk factors. METHODS: 220 episodes of neutropenic fever in 177 cancer patients have been reviewed. RESULTS: Infections could be documented microbiologically in 38 (17.3%) episodes and suspected clinically in 29 (13.2%). The most common focus of infection was the lower respiratory tract (11.4%) followed by the urinary tract (6.4%). The most frequently isolated pathogen was Escherichia coli (31%) followed by Klebsiella pneumoniae (18%), Pseudomonas aeruginosa (13%) and Streptococcus pneumoniae (13%). The median durations of neutropenia and fever were 4 and 3 days, respectively. Mortality was seen in 25 patients (11.4%). Its rate was higher in documented infections except for non-bacteremic microbiologic infections in which no death was seen. Hypotension and shock were the most significant determinants of poor prognosis. CONCLUSIONS: The management of these special patients should be given adequate attention and be considered important since the success of therapy depends on revealing of etiologic agents.     

Infectious complications during remission induction therapy in 577 patients with acute myeloid leukemia in the Japan Adult Leukemia Study Group studies between 1987 and 1991

The Japan Adult Leukemia Study Group analyzed infectious episodes in 577 patients with acute myeloid leukemia during remission induction therapy between 1987 and 1991. 542 patients (93.9%) experienced at least one infectious episode, 121 (21.0%) had microbiologically documented infection; there was clinically documented infection in 184 (31.9%) and unexplained fever in 237 (41.1%). Among 121 microbiologically documented infections, bacteremia/fungemia was observed in 68, pneumonia in 33, and other types of infections in 20. Among the bacteremia/fungemia, gram-negative bacteria accounted for 41.2% (Pseudomonas aeruginosa was the most common), gram-positive bacteria for 39.7%, fungi for 16.2% (Candida spp. being most frequent), and polymicrobial for 2.9%. The most frequent isolates among pneumonia were Pseudomonas aeruginosa and Aspergillus. A total of 70 patients (12.1%) died during remission induction. Mortality of 68 patients with bacteremia/fungemia was 26.5%; in these patients, mortality with concomitant pneumonia increased to 41.4%; without pneumonia, mortality was 15.4% (P < 0.05). Mortality according to the isolated microbes was 17.2% for gram-negative bacteria, 25% for gram-positive bacteria, and 54.5% for fungi. Mortality of 113 patients with pneumonia (33 microbiologically documented and 80 clinically documented), 20 with other microbiologically documented infections, 104 with other clinically documented infections, and 237 with unexplained fever was 25.7%, 5.0%, 5.8%, and 5.1%, respectively.     

Autologe hämatopoetische Stammzelltransplantation bei systemischem Lupus erythematodes

Although the treatment options for systemic lupus erythematosus (SLE) have significantly improved over the past years through the introduction of novel targeted biologic therapies, there are still some patients who suffer from refractory and potentially life-threatening courses of the disease. For these patients autologous hematopoietic stem cell transplantation (ASCT) after immunoablative chemotherapy provides a promising treatment option with curative potential. Based on preclinical models, ASCT was first introduced in 1996 and has since been carried out in approximately 300 patients worldwide. Clinical study results confirmed a disease-free survival in approximately 50?% of patients after 5 years despite termination of immunosuppressive treatment. By careful patient selection and improved anti-infection prophylaxis during stem cell therapy, transplantation-associated mortality could be reduced from an initial 13?% to currently an average of 6?%. Meanwhile, mechanistic studies have provided proof of concept that ASCT not only exerts intensified immunosuppressive effects but is also associated with fundamental qualitative changes of the immune system that may rewire a chronic autoimmune system into a naïve and self-tolerant state: in other words immune reset. Overall, ASCT for SLE is still reserved for patients who do not sufficiently respond to standard therapy. Treatment should be carried out in close cooperation with centers specializing in hematology and only within the framework of clinical studies.     

A prospective study of infections in lung cancer patients admitted to the hospital

STUDY OBJECTIVES: To determine the type of infections occurring in hospitalized patients with lung cancer. DESIGN: Prospective cohort study. SETTING: Department of internal medicine in a cancer hospital. PATIENTS: All patients with lung cancer who were hospitalized for any cause and who acquired infections at the time of admission or during the hospital stay between January 1997 and February 2001. INTERVENTIONS: None. RESULTS: Two hundred seventy-five patients with lung cancer had 435 episodes of fever and/or microbiologically or otherwise documented infection. Two hundred eighteen patients (79.3%) presented with non-small cell lung carcinoma, while 49 patients (17.8%) had small cell lung cancer. The majority of the infections occurred in the tracheobronchial tree (56%). There were 38 episodes of bacteremia or fungemia, and the primary site of infection was identified in 18 cases (47%). Microbiologically documented infections accounted for 61% of the infectious episodes, and included a total of 312 microorganisms. The most frequent pathogens were Gram-negative bacteria (64%), followed by Gram-positive bacteria (25%) and fungi (8%). The predominant Gram-negative bacteria were Haemophilus influenzae and Moraxella catarrhalis. Staphylococcus aureus, Streptococcus pneumoniae, coagulase-negative staphylococci, and Enterococcus faecalis essentially represented the Gram-positive bacteria. No multiresistant bacteria were observed. Bacteria were susceptible to most of the antibiotics classically administered for their treatment. CONCLUSIONS: The predominant site of infection in patients with lung cancer is the tracheobronchial tree, with S pneumoniae, S aureus, H influenzae, Escherichia coli, Pseudomonas aeruginosa, and M catarrhalis as the principal pathogens.     

Patterns of infection in patients with aplastic anemia and the emergence of Aspergillus as a major cause of death.

Patterns of infection were studied in 150 patients with aplastic anemia who were admitted to the Clinical Hematology Branch, National Institutes of Health, between January 1978 and December 1989 for immunosuppressive therapy. Sixty percent of the patients were males, 71% were white, their mean age was 33.6 years (median, 27.5; range, 1-75), and 83% had severe aplastic anemia. One hundred three patients developed 1 or more febrile episodes during the study period. The risk factors for developing a febrile episode included a low Absolute Neutrophil Count (ANC) and Absolute Monocyte Count (AMC) at admission and the presence of an indwelling central venous catheter (Hickman-Broviack or Port-A-Cath). A total of 289 febrile events were studied, including unexplained fever (FUO) in 89 (31%), microbiologically documented infection (MBDI) in 137 (47%), and clinically documented infection (CDI) in 63 patients (22%). Compared to documented infections (MBDI) or CDI), FUO events were associated with a higher frequency of rigors, signs and symptoms of serum sickness, and treatment regimens known to cause fevers. None of the FUO events had a fatal outcome, even if the antibiotic therapy was discontinued before day 7. Among CDI events, bacteria were the most commonly defined etiologic agent (67%), followed by fungi (23%), viruses (7%), and parasites (3%). The patterns of bacterial infections in patients with aplastic anemia were similar to those observed in patients with cancer-related neutropenia. Twenty-one patients (15%) developed invasive fungal infections (aspergillus, 11; candida, 7; and both, 3), which were fatal in 19 (90%). Fungal infections accounted for 30% of the secondary infectious events and for 55% of fatal infectious events. The only identifiable risk factors for developing a fungal infection were the degree of neutropenia and monocytopenia at initial admission or final evaluation. Invasive pulmonary aspergillosis developed despite empirical amphotericin B therapy and was associated with a high incidence of fatal pulmonary hemorrhage (10 of 13 patients [77%]). Infection was responsible for 36 (62%) of the deaths observed during the study period and hemorrhage alone for 4 (7%). However, 20 of the patients who died of infection had concomitant hemorrhage. No significant drop in ANC, AMC, or platelet count could be demonstrated during a fatal infectious event as compared to a nonfatal infectious event. Invasive fungal infections, predominantly with aspergillus and candida, emerged in our study as the major causes of mortality in patients with aplastic anemia. Without bone marrow recovery the prognosis associated with invasive mycoses was grave.     

Early infections in adult patients undergoing unrelated donor cord blood transplantation

Early transplant-related mortality after cord blood transplantation from unrelated donors (UD-CBT) is close to 50%, mainly due to infectious complications. We have studied the incidence and characteristics of early infections (before day 100) in a series of 27 adult patients (median age 30 years, range 16-46) undergoing UD-CBT at a single institution. All 27 patients experienced at least one infectious episode and 18 (66%) suffered a severe infection. Bacteremia occurred in 55% of patients (13 with Gram-positive and 11 with Gram-negative microorganisms). Eleven of 19 CMV-seropositive patients (58%) developed CMV antigenemia and one patient had CMV disease. Fungal infections were documented in three patients (11%), comprising invasive fungal infections in two cases and a localized esophagitis in one. Ten patients (37%) died before day 100 after transplantation. Infection was considered the primary cause of death in four patients (sepsis by Acinetobacter spp. bacteremia in three cases) and contributed to death in another four. The most striking findings in this series were the high incidence of, and mortality due to multiresistant Acinetobacter spp. and the low incidence of and lack of mortality due to CMV disease. This report confirms that infection is a major complication in adults undergoing UD-CBT.     

Impact of pretransplant therapy in patients with newly diagnosed myeloma undergoing autologous SCT

Autologous SCT (ASCT) remains an effective therapy for eligible patients with myeloma. Previous studies have suggested a lack of impact of the initial therapy on the outcome after ASCT. It is not clear if incorporation of new agents in the initial treatment regimens will have any impact on the outcome after ASCT. We studied 472 patients undergoing ASCT within 12 months of diagnosis to assess the effect of initial therapy on the outcome after ASCT. Patients received initial therapy with vincristine, adriamycin and dexamethasone (VAD), dexamethasone, thalidomide and dexamethasone or lenalidomide and dexamethasone. While patients treated with dexamethasone alone had higher disease burden at ASCT, no differences were observed in the response rates to ASCT, post transplant complications or treatment-related mortality among the groups. The median time to progression after ASCT was 27.1, 24.7, 21.1 months and did not reach the VAD, Dex, Thal-Dex and Len-Dex group, respectively, P=0.11. The median overall survival from ASCT was 62 months for VAD, 69.6 months for Dex and were not reached for Thal-Dex and Len-Dex groups, P=0.2. For patients undergoing early ASCT for myeloma, the nature of initial treatment utilized has no long-term impact on the outcome of ASCT.     

Infective endocarditis--analysis of 116 surgically and 26 medically treated patients

We have reviewed 116 cases of bacterial endocarditis treated surgically and 26 cases treated medically since 1973. There were 123 patients with native valve endocarditis and 19 patients with prosthetic valve endocarditis. Overall, the left-sided valves were infected most frequently. There were 10 cases with right-sided valves involved. Multiple valves were infected in 6 patients. There were 6 perioperative deaths in the surgical group. The most common cause of death was multi-organ failure associated with uncontrollable sepsis. The overall operative mortality for active endocarditis was 7.7% (4/55), and for healed endocarditis, 3.3% (2/61). For active native valve endocarditis, the mortality was 4.2% (2/48), for healed native valve endocarditis, 3.6% (2/55), for active prosthetic valve endocarditis, 28.6% (2/7), and for healed prosthetic valve endocarditis, 0%. There was no difference in the operative mortality between active native valve endocarditis and healed native valve endocarditis. The mortality of active prosthetic valve endocarditis was significantly higher than that of active native valve endocarditis (p less than 0.01). Of the 26 patients treated medically, 7 died during the initial hospitalization. The major factor related to mortality in the medically treated patients was persistent sepsis (four patients), and congestive heart failure (three patients). The overall mortality of the medical group for active valve endocarditis was 15% (3/20), and for active prosthetic valve endocarditis, 67% (4/6). We conclude that patients with infective endocarditis with significant valve lesions who are unresponsive to medical therapy should be considered for urgent surgery.