Search

Hamstrings identification and subsequent graft harvest can be made difficult by body habitus and variability in tendon anatomy. We describe a 'sentinel' blood vessel near the insertions of gracilis and semitendinosus to facilitate identification. A prospective study of 100 patients (100 knees) undergoing primary arthroscopic ACL reconstruction (via the anterior approach) with hamstrings graft was conducted. We searched for a 'sentinel' vessel and studied its position, orientation and perpendicular distance from the pes tendons. The 'sentinel' vessel was present in 98/100 knees. It passed from the superficial fascia to the periosteum at the pes insertion at a mean perpendicular distance of 8 mm from the upper border of the pes tendons. The 'sentinel' vessel was a consistent anatomical finding and served as a reliable guide in determining the pes insertion. Identifying this anatomical landmark allowed a small skin incision with limited wound dissection minimising risk of injury to the infra-patellar branch of the saphenous nerve.

Purpose: Patellofemoral osteoarthritis (PFOA) occurs in approximately half of anterior cruciate ligament (ACL)-injured knees within 10–15 years of trauma. Risk factors for post-traumatic PFOA are poorly understood. Patellofemoral alignment and trochlear morphology may be associated with PFOA following ACL reconstruction (ACLR), and understanding these relationships, particularly early in the post-surgical time period, may guide effective early intervention strategies. In this study, patellofemoral alignment and trochlear morphology were investigated in relation to radiographic features of early PFOA 1-year post-ACLR. Methods: Participants (aged 18–50 years) had undergone ACLR approximately 1 year prior to being assessed. Early PFOA was defined as presence of a definite patellofemoral osteophyte on lateral or skyline radiograph. Sagittal and axial plane alignment and trochlear morphology were estimated using MRI. Using logistic regression, the relationship between alignment or morphology and presence of osteophytes was evaluated. Results: Of 111 participants [age 30 ± 8.5; 41 (37%) women], 19 (17%) had definite osteophytes, only two of whom had had patellofemoral chondral lesions noted intra-operatively. One measure of patellar alignment (bisect offset OR 1.1 [95% confidence interval 1.0, 1.2]) and two measures of trochlear morphology (sulcus angle OR 1.1 [1.0, 1.2], trochlear angle OR 1.2 [1.0, 1.5]) were associated with patellofemoral osteophytes. Conclusions: Patellofemoral malalignment and/or altered trochlear morphology were associated with PFOA 1 year following ACLR compared to individuals post-ACLR without these features. Clarifying the role of alignment and morphology in post-traumatic PFOA may contribute to improving early intervention strategies aimed at secondary prevention. Level of evidence: IV.

Rupture of the anterior cruciate ligament (ACL) is a common and debilitating injury that impacts significantly on knee function and risks the development of degenerative arthritis. The outcome of ACL surgery is not monitored in Australia. The optimal treatment is unknown. Consequently, the identification of best practice in treating ACL is crucial to the development of improved outcomes. The Australian Knee Society (AKS) asked the Australian Orthopaedic Association (AOA) to consider establishing a national ACL registry. As a first step, a pilot study was undertaken by the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) to test the hypothesis that collecting the required information in the Australian setting was possible. Surgeons completed an operative form which provided comprehensive information on the surgery undertaken. Patients provided pre- and post-operative questionnaires including the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Marx Activity Scale (MA Scale). The number of ACL procedures undertaken at each hospital during the recruitment period was compared against State Government Health Department separation data. A total of 802 patients were recruited from October 2011 to January 2013. The overall capture rate for surgeon-derived data was 99%, and the capture rate for the pre-operative patient questionnaire was 97.9%. At 6 months, patient-reported outcomes were obtained from 55% of patients, and 58.5% of patients at 12 months. When checked against State Government Health Department separation data, 31.3% of procedures undertaken at each study hospital were captured in the study. It is possible to collect surgeon-derived and pre-operative patient-reported data, following ACL reconstruction in Australia. The need to gain patient consent was a limiting factor to participation. When patients did consent to participate in the study, we were able to capture nearly 100% of surgical procedures. Patient consent would not be an issue in for a national registry where inclusion is automatic unless the patient wishes to opt out. The collection of post-operative patient-reported outcome measures (PROMs) is more problematic, due to an insufficient proportion of individuals providing patient-reported outcomes. Alternative outcome measures are required for an ACL registry in Australia to be successfully implemented. Diagnostic, Level III.

Purpose>/b> Impairments in quadriceps force control and altered quadriceps and hamstring muscle activation strategies have been observed following anterior cruciate ligament reconstruction; however, the functional implications of these impairments are unclear. This study examined the cross-sectional associations between quadriceps force control, quadriceps activation, hamstring coactivation and clinically assessed knee function following anterior cruciate ligament reconstruction with a hamstring graft. Methods Sixty-six patients (18 ± 3 months following surgery) and 41 uninjured individuals participated. Quadriceps force control was assessed using an isometric knee extension task. Participants cyclically increased and decreased quadriceps force at slow speeds between 5 and 30 % maximum voluntary isometric contraction matching a moving target displayed on a screen. Quadriceps activation and hamstring coactivation were assessed concurrently using surface electromyography. Knee function was assessed with the Cincinnati Knee Rating Scale and three single-leg hop tests. Results The reconstructed group completed the task with 48 % greater root-mean-square error (RMSE), indicating significantly worse quadriceps force control (p < 0.001). In a multivariable model adjusted for sex, greater RMSE and greater lateral hamstring coactivation were significantly associated with worse knee function that is greater odds of scoring

Individuals with impaired knee function after anterior cruciate ligament reconstruction (ACLR) may be at greater risk of developing knee osteoarthritis related to abnormal knee joint movement and loading. The aim of this study was to assess the association between knee biomechanics and knee laxity during hopping and clinically assessed knee function (i.e., patient-reported knee function and hop tests) following ACLR. Sixty-six participants (23 women, mean age 28 ± 6 years, mean 18 ± 3 months following ACLR) completed a standardized single-leg hopping task. Three-dimensional movement analysis was used to assess knee flexion excursion and body weight/height normalized knee flexion moments during landing for the involved limb. Anterior–posterior knee laxity was assessed with a KT-1000 knee arthrometer. Participants then completed a patient-reported knee function questionnaire and three separate hop tests (% of uninvolved limb) and were divided into poor and satisfactory knee function groups (satisfactory: ≥85% patient-reported knee function and ≥ 85% hop test symmetry). Associations between knee function and hop biomechanics/knee laxity were assessed using logistic regression and interquartile range scaled odds ratios (ORIQR). Greater knee flexion excursion (ORIQR 2.9, 95%CI 1.1–7.8), greater knee flexion moment (ORIQR 4.9, 95%CI 1.6–14.3) and lesser knee laxity (ORIQR 4.7, 95%CI 1.5–14.9) were significantly associated with greater odds of having satisfactory knee function (≥ 85% patient-reported knee function and ≥ 85% hop test symmetry). Greater knee flexion excursion/moment during hop-landing and lesser knee laxity is associated with better patient-reported knee function and single-leg hop test performance following ACLR. Patients with lower levels of knee function following ACLR demonstrated hop-landing biomechanics previously associated with early patellofemoral osteoarthritis. Therefore, interventions aimed at improving hop landing biomechanics in people with poor knee function are likely required. III, Cross-sectional study.

Poor knee function after anterior cruciate ligament reconstruction (ACLR) may increase the risk of future knee symptoms and knee osteoarthritis via abnormal knee joint loading patterns, particularly during high-impact activity. This study aimed to assess the relationship between poor self-reported or clinically measured knee function and knee moments/vertical ground reaction force (vGRF) in individuals following ACLR. 61 participants (mean 16.5 ± 3 months following ACLR, 23 women) completed a patient-reported knee function questionnaire and three hop tests (% of uninvolved limb). Participants were divided into satisfactory and poor knee function groups (poor

Introduction We report the first non-designer study of the Unix uncemented unicompartmental knee prosthesis. Materials and methods Eighty-five consecutive UKRs were carried out with sixty-five available for follow-up. Oxford Knee Scores, WOMAC questionnaire and radiological assessment were completed. Results The mean Oxford Knee Score was thirty-eight and WOMAC Score was twenty. Overall Kaplan Meier survival estimate is 76% (95% confidence interval 60%–97%) at 12 years and 88% (95% confidence interval 76–100%) with aseptic loosening as the endpoint. Radiographic assessment showed lysis in the tibia in 6% of patients with no lysis evident around the central fin. Discussion Survivorship is comparable to other published series of UKRs. We suggest the central fin design is key to dissipating large forces throughout the proximal tibia, resulting in low levels of tibial loosening. Level of evidence IV.

Individuals following anterior cruciate ligament reconstruction (ACLR) with concomitant meniscal pathology have a higher risk of developing knee osteoarthritis (OA) compared to those with isolated ACLR. Knee extensor weakness and altered dynamic knee joint biomechanics have been suggested to play a role in the development of knee OA following ACLR. This study investigated whether these factors differ in people following ACLR who have concomitant meniscal pathology compared to patients with isolated ACLR. Thirty-three patients with isolated ACLR and 34 patients with ACLR and meniscal pathology underwent strength and gait assessment 12–24 months post-operatively. Primary measures were peak isometric knee extensor torque and knee adduction moment (peak and impulse). Secondary measures included peak knee flexion moment and knee kinematics (sagittal and transverse). There were no between-group differences in knee extensor strength [mean difference (95 % CI) 0.09 (−0.23 to 0.42) Nm/kg, n.s.], peak knee adduction moment [−0.02 (−0.54 to 0.49) Nm/(BW × HT) %, n.s.] or knee adduction moment impulse [0.01 (−0.15 to 0.17) Nm/(BW × HT) %, p = n.s.]. No between-group differences were found for any secondary measures. No evidence was found to suggest that the higher prevalence of OA in patients with ACLR and meniscal pathology compared to patients with isolated ACLR is attributed to reduced knee muscle strength or altered knee joint biomechanics assessed 1–2 years post-surgery. Given that there is a higher incidence of knee OA in patients with concomitant meniscal pathology and ACLR, further investigation is needed so that population-specific rehabilitation protocols can be developed. III.

To determine whether the presence of magnetic resonance imaging (MRI) osteoarthritis (OA) features in the patellofemoral or tibiofemoral joint (i.e., bone marrow lesions, cartilage lesions, and osteophytes) and/or functional impairments, 1 year following anterior cruciate ligament reconstruction (ACLR), can predict Knee Injury and Osteoarthritis Outcome Score (KOOS) at 3 years.A total of 93 participants (56 [60%] men, mean ± SD age 29 ± 9 years) who had undergone MRI examination and functional testing at 1-year post-ACLR, completed the KOOS at 3 years postsurgery. Multivariate regression models evaluated the prognostic capacity of compartment-specific osteochondral OA features, scored using the MRI Osteoarthritis Knee Score, and functional performance (hop for distance, 1-leg rise), to predict outcome on 4 KOOS subscales (pain, symptoms, sport/recreation, and quality of life [QOL]).Presence of patellofemoral cartilage lesions 1-year post-ACLR predicted worse score on all KOOS subscales at 3 years (P ≤ 0.01). Regression coefficients (B) were -5.1 (95% confidence interval [95% CI] -9.1, -1.2) for symptoms, -4.0 (95% CI -6.7, -1.4) for pain, -6.7 (95% CI -11.0, -2.4) for sport/recreation, and -8.6 (95% CI -15.1, -2.1) for QOL. No significant associations were found between tibiofemoral MRI features and knee symptoms. Poorer performance on the 1-leg-rise test predicted worse KOOS-QOL (B -6.5 [95% CI -12.4, -0.5], P = 0.03).The presence of a patellofemoral articular cartilage lesion and lower 1-leg-rise performance at 1 year postsurgery are prognostic for poorer 3-year outcome following ACLR. Particular attention to patellofemoral compartment lesions and functional capacity is warranted during postoperative rehabilitation programs, as these features represent potential targets for therapy aimed at minimizing symptomatic disease progression in these young adults.

While training upregulates skeletal muscle Na(+), K(+)-ATPase (NKA), the effects of knee injury and associated disuse on muscle NKA remain unknown. This was therefore investigated in six healthy young adults with a torn anterior cruciate ligament, (KI; four females, two males; age 25.0 ± 4.9 years; injury duration 15 ± 17 weeks; mean ± SD) and seven age- and BMI-matched asymptomatic controls (CON; five females, two males). Each participant underwent a vastus lateralis muscle biopsy, on both legs in KI and one leg in CON. Muscle was analyzed for muscle fiber type and cross-sectional area (CSA), NKA content ([(3)H]ouabain binding), and α1-3 and β1-2 isoform abundance. Participants also completed physical activity and knee function questionnaires (KI only); and underwent quadriceps peak isometric strength, thigh CSA and postural sway assessments in both injured and noninjured legs. NKA content was 20.1% lower in the knee-injured leg than the noninjured leg and 22.5% lower than CON. NKA α2 abundance was 63.0% lower in the knee-injured leg than the noninjured leg, with no differences in other NKA isoforms. Isometric strength and thigh CSA were 21.7% and 7.1% lower in the injured leg than the noninjured leg, respectively. In KI, postural sway did not differ between legs, but for two-legged standing was 43% higher than CON. Hence, muscle NKA content and α2 abundance were reduced in severe knee injury, which may contribute to impaired muscle function. Restoration of muscle NKA may be important in rehabilitation of muscle function after knee and other lower limb injury.

Magnetic resonance imaging (MRI) is the most widely used non-invasive test for assessing intra-articular injuries of the knee. It has been suggested that a negative MRI can be useful in avoiding the need for diagnostic arthroscopy in cases where clinical examination is equivocal. However, the sensitivity and specificity of MRI is not 100%, particularly for tears of the lateral meniscus. Furthermore, a false negative MRI scan may result in premature return to play in athletes, resulting in increased risk of further damage to a torn meniscus. To illustrate this issue, we present a case series of eight elite athletes who all presented with mechanical knee symptoms and where MRI scans revealed no significant intra-articular pathology. Five of the athletes were allowed to return to sport on the basis of a negative MRI. All patients were subsequently found to have a bucket-handle tear of their lateral meniscus at arthroscopy. Two independent, experienced musculoskeletal radiologists were asked to review the MRI films without being given any clinical history of the cases. Although injuries to the popliteus tendon were noted in two of the athletes who had sustained a recent acute injury to their knee, no meniscal tears were identified. Thus arthroscopy remains the gold standard for the assessment and management of high-demand patients with a clinical suspicion of meniscal pathology.

We present 3 cases of arthroscopically treated intraarticular osteoid osteoma of the ankle. Emphasis is on the high index of suspicion for this lesion, the appropriate imaging modality and the efficacy of arthroscopic excision of these tumors with superficial location in the talus and tibial plafond.

Summary. Between January 1987 and January 1997, 69 eligible patients with acute myeloid leukaemia (AML) in either second (CR2) or third (CR3) complete remission (CR2 = 60, CR3 = 9) underwent 4-hydroperoxycyclophosphamide-purged autologous bone marrow transplantation (BMT) at the Johns Hopkins Oncology Center. The patients' median age was 27 years (range 1–62) and all received busulphan and cyclophosphamide as their preparative regimen. The probability of event-free survival (EFS) at 5 years was 30%[95% Confidence Interval (CI): 19–42%] for CR2 patients and 22% (3–51%) for those in CR3, with a median follow up of 8 years in the surviving group. The median time to an absolute neutrophil count of 0·5 × 109/l was 45 d (range 20–185). Relapse was the major cause of failure with a relapse rate of 55% in CR2 and 44% in CR3, while the non-relapse, transplant-related mortality rate was 15% in CR2 and 33% in CR3. In univariate analysis, patient age, cytogenetics, white blood cell count at presentation, CR1 duration and the sensitivity of clonogeneic leukaemia (CFU-L) in the graft to 4HC were all prognostic for EFS. Using each of these significant variables in multivariate modelling, patient age and sensitivity of CFU-L to 4HC were determined to be predictors of EFS. 4HC-purged autologous BMT produced results similar to allogeneic BMT for AML patients beyond first remission.

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.

Background. Hemorrhagic complications are frequently implicated clinically for the high morbidity and mortality of acute graft versus host disease (GVHD), however, only few reports characterize the incidence and timing of bleeding in relation to GVHD, and essentially no study has quantified the effect of bleeding on survival of allogeneic patients with GVHD. This study examines the association of bleeding with acute GVHD and the effect of both complications on survival. Methods. A total of 463 allogeneic patients transplanted at the Johns Hopkins Hospital, were included in the study. Bleeding evaluation was based on daily scores of intensity and blood transfusions. All bleeding sites were recorded. GVHD staging was defined by the extent of rash, serum bilirubin, diarrhea, and confirmatory histology. Results. The incidence of GVHD was 27.4%, bleeding occurred in 40.2%. The incidence of bleeding was higher in patients with GVHD as compared with non-GVHD, and correlated with GVHD severity. The higher bleeding incidence in GVHD was due to gastrointestinal hemorrhage, hemorrhagic cystitis, and pulmonary hemorrhage. While the majority of bleeding (51/75) in non-GVHD patients initiated within 30 days after bone marrow transplantation (BMT), only 32.3% (21/65) of the bleeding in the GVHD group initiated within 30 days, and the risk for bleeding continued until day 100. Bleeding was a late event compared to GVHD, however, most bleeding episodes were associated with active GVHD. Both GVHD and bleeding were individually associated with reduced survival, with profound additive adverse effect: median survival in 221 nonbleeding non-GVHD was >83.2 months, GVHD nonbleeding (39 patients) had median of 10.6 months, bleeding non-GVHD (99 patients) had median of 4.3 months, and median survival of the GVHD bleeding group (85 patients) was 3.2 months. Conclusions. Our results support an association of bleeding with acute GVHD, suggesting that GVHD is a risk factor for bleeding after BMT. The occurrence of bleeding clearly identified poor outcome subgroup within GVHD, suggesting further evaluation for clinical application of bleeding in the assessment of GVHD severity.

Inadequate polyethylene thickness is a risk factor in the development of polyethylene wear in unicompartmental knee arthroplasty (UKA). The labelled thickness of polyethylene inserts often refers to the combined thickness of the insert and its metal backing. However specific information regarding the actual minimum thickness of the polyethylene is seldom available. We sought to determine the actual minimum thickness of polyethylene inserts used in five contemporary metal-backed UKA designs. The thinnest available insert from each of these designs was identified and measured at the lowest point of its concave articulating surface with a Kincrome electronic digital micrometer. The minimum thickness of the inserts ranged from 3.702 mm to 7.859 mm (mean values). In two of the inserts, the minimum thickness was found to be less than the recommended minimum thickness of 6 mm. Implant manufacturers should clearly indicate the actual minimum thickness of polyethylene inserts on their product labels.

Background and Methods. Thrombotic thrombocytopenic purpura—hemolytic uremic syndrome (TTP-HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, fever, central nervous system abnormalities, and renal dysfunction. In early reports the mortality approached 100 percent. A treatment protocol was introduced in 1979 for patients admitted to Johns Hopkins Hospital with the diagnosis of TTP-HUS. Treatment regimens included 200 mg of prednisone a day, for patients with minimal symptoms and no central nervous system symptoms, and prednisone plus plasma exchange, for patients with rapid clinical deterioration who did not improve after 48 hours of prednisone alone and for patients presenting with central nervous system symptoms and rapidly declining hematocrit values and platelet counts. Results. A total of 108 patients were treated, and 91 percent survived. Prednisone alone was judged to be effective in 30 patients with mild TTP-HUS (2 relapses and 2 deaths). Plasma exchange plus pre...

This case report describes a 20-year-old elite-level Australian Rules football player who suffered three unilateral hamstring injuries within a 2 month period. The first two episodes were managed conservatively. Magnetic resonance imaging following the third episode revealed full thickness disruption of the proximal musculotendinous junction of the biceps femoris long head and semitendinosus muscles and the common proximal (conjoint) tendon. The injury was subsequently surgically repaired. At 16 months following surgery, the player had successfully completed a full competitive season of elite-level Australian Rules football symptom free. Follow-up magnetic resonance imaging demonstrated the repaired tendon to be uniformly hypointense in keeping with reparative granulation tissue formation and restoration of normal muscle morphology. These findings are consistent with an intact repair. The case demonstrates that complete functional and radiological resolution is possible following surgical repair of significant hamstring musculotendinous junction tears.

R ED CELL, platelet, plasma, and a variety of plasma fractions are available at most fullservice hospitals. However, other component support services such as granulocyte transfusion, bone marrow transfusion, or biologic response modifiers may be available only through tertiary care centers due to their investigational nature or a need to focus use of scarce or expensive resources. These more specialized aspects of transfusion support for the oncology patient may not be used by the oncology nurse in daily clinical practice, but a sound knowledge basis of these technologies is essential if the practicing nurse is to remain an advocate of the patient's therapy and a knowledgeable resource for patient education. This article will present the biologic basis and principles of clinical practice involved with aspects of selected newer technologies including granulocyte transfusion, bone marrow transfusion, blood irradiation, cytomegalovirus (CMV) negative blood support, and clinical uses of biological response modifiers.

We prospectively evaluated infusion-related toxicities in 82 recipients of autologous bone marrow grafts. The grafts were cryopreserved in 10% dimethylsulfoxide and stored in liquid nitrogen. All grafts were concentrated and buffy-coat cells were collected. Forty-seven grafts were treated ex vivo with 4-hydroperoxycyclophosphamide (4-HC) at 100 micrograms/mL; 26 grafts were further processed using density-gradient separation and treated with 4-HC at 60 micrograms/mL. Nine buffy-coat concentrates were frozen without drug treatment. Before infusion, patients were medicated with mannitol, hydrocortisone, and diphenhydramine. Grafts were rapidly thawed and immediately infused without further manipulation. During the infusions, 33 (70%) recipients of treated buffy-coat, 5 (56%) recipients of untreated buffy-coat, and 6 (23%) recipients of density-gradient separated grafts experienced varying symptoms including nausea, abdominal cramping, and flushing. Forced vital capacities for 83% of the recipients of treated buffy-coat concentrates decreased after the graft infusion; six of these patients complained of dyspnea and one patient experienced an acute episode of respiratory decompensation. Decreased heart rates were observed in 98% of the recipients of treated buffy-coat cells with asymptomatic bradycardia occurring in 45%. Forty-five patients (96%) in this group experienced transient hypertension, with 18 (38%) requiring additional medications within 6 hours after the infusion for control of blood pressure. Similar cardiovascular changes were observed in the recipients of untreated buffy-coat concentrates. One recipient of an untreated buffy-coat concentrate had 2 degrees heart block after the graft infusion. Twenty-three (88%) recipients of density-gradient separated grafts had decreased heart rates and 21 (81%) had increased blood pressure. However, the degrees of change were less than those experienced by the recipients of treated buffy-coat cells (P less than .01). Forced vital capacities were not affected by the infusion of the density-gradient separated grafts. No renal failure or obvious hemolytic episodes occurred for any patient group. Minor to moderate toxicities were associated with cryopreserved graft infusions. Recipients of buffy-coat separated grafts, both treated and untreated, experienced more complications than the recipients of density-gradient separated grafts. These toxicities may relate to the volumes of cryoprotectant and cell lysis products infused, which were less for the more highly purified density-gradient separated grafts.

Revision ACL reconstruction poses several challenges for the surgeon in terms of the timing of surgery and the limited graft choices. To our knowledge, there is currently no published data with regards to revision ACL reconstruction in a child. We describe the case of a 12-year-old girl who had a re-injury 4.5 months after her index primary ACL reconstruction at the age of 11 years. She sustained a repeat injury to the reconstructed knee following a road traffic accident and developed significant instability despite an intensive rehabilitation program. After careful consideration of the available graft materials – known all the advantages and disadvantages of the autografts, allografts and synthetic materials – we decided to use the patient's mother's hamstrings as a graft. The parents of our patient refused the use of allograft and synthetic materials. We discuss our management of this case, the reasons for our revision graft choice, and the theoretical disadvantages of some of the alternative graft choices available in this scenario. We believe in such cases, performing ACL revision with a donor graft of the patient's mother could be good alternative to allografts or synthetic grafts.

This study investigates whether the amount of tibial and femoral bone tunnel enlargement following anterior cruciate ligament (ACL) reconstruction with hamstrings can be reduced by compaction bone tunnel drilling.Patients undergoing primary ACL reconstruction with four-strand hamstrings (n = 26) were matched to either extraction drilling (n = 13) or compaction drilling (n = 13). Extracortical femoral fixation was by means of a 20 mm Endobutton CL and tibial fixation was by resorbable interference screw. A CT scan was performed on the second postoperative day and an average of 4 months (range 3.8-5 months) postoperatively in all patients. Tunnel enlargement was determined by digitally measuring the widths perpendicular to the long axis of the tunnels on an oblique coronal and axial plane. The CT measurements were compared to the intraoperative drill diameter.With extraction drilling the average tibial tunnel diameter proximal to the interference screw increased from 8.5 to 10.4 mm (P0.0001) and the average femoral tunnel from 8.0 to 10.6 mm (P0.0001). With compaction drilling it increased from 8.2 to 10.0 mm (P0.0001) and from 7.6 to 9.7 mm (P0.002), respectively. Tunnel widening was 22% on the tibial side for both groups and 33 versus 28% on the femoral side (P = 0.09) for extraction versus compaction drilling.There was a significant tibial and femoral tunnel widening on CT an average of only 4 months following ACL reconstruction with hamstrings. Compaction drilling with a stepped router did not prove to reduce the postoperative tunnel widening significantly. Tunnel widening was higher on the femoral side which could be related to the extracortical femoral fixation technique.Level 4.

The advantages of the prosthetic replacement after resection of bone tumours include: 1) relatively simple technique, 2) modularity, 3) immediate function, 4) no disease transmission, 5) arthroplasty is possible. The disadvantages include: 1) late complications-asceptic loosening, bearing failure, fracture, 2) muscle re-attachment, 3) bone stock loss.

New research has changed our perception and management of common injuries. Magnetic resonance imaging and arthroscopy of the hip have shown that labral injuries, chondral injuries, rim lesions, synovitis and tears of the ligament teres are common causes of hip, groin and low-back pain. Hip arthroscopy is used both as a diagnostic and therapeutic tool; it has been shown to be of benefit in recent traumatic labral injury, but disappointing in the management of chronic hip pain (which may be associated with degenerative change, and chondral lesions of the acetabulum). The McConnell multimodal physiotherapy regimen is effective in treating patellofemoral pain. Anterior cruciate ligament rupture is three to five times more common in women, but neuromuscular training appears to decrease its incidence. Patellar tendon and hamstring grafts appear to be equally effective in anterior cruciate ligament reconstruction. Articular cartilage defects remain a significant problem, and the efficacy of treatments such as autologous chondrocyte implantation is still unclear.

Opening wedge high tibial osteotomy (OWHTO) is a recently described procedure for medial compartment arthritis of the knee in the active, younger population. Despite having a number of advantages over the traditional closing wedge high tibial osteotomy (CWHTO) a potential complication of OWHTO is a high rate of delayed- and non-union. This study reports the occurrence of delayed- and non-union following OWHTO for medial compartment arthritis of the knee. Questionnaires were sent to all current members of the Australian Knee Society (n=45), a special interest group of the Australian Orthopaedic Group. Surgeons were asked primarily to indicate how many OWHTOs they had performed, and how many of these had progressed to union, delayed-union and non-union. All 45 questionnaires were returned, with 21 surgeons (47%) performing OWHTOs. A total of 188 OWHTO cases were reported, of which 182 were complete. Of these complete cases 167 (91.8%) were classed as united, 12 (6.6%) delay-united and 3 (1.6%) non-united. The results of this study demonstrate that the rate of delayed- and non-union following OWHTO for medial compartment arthritis of the knee is relatively low and comparable to that reported for traditional CWHTO.

BACKGROUND: Septic platelet transfusion reactions (SPTRs) are the most common, serious risk of transfusion. Because SPTRs result from donor skin flora or asymptomatic bacteremia, the use of single-donor platelets (SDPs) has been proposed to reduce the risk of SPTRs from the risks with pools of platelet concentrates (PCs). STUDY DESIGN AND METHODS: Beginning in 1986, all febrile transfusion reactions were evaluated by culture of the platelet bag. Confirmed SPTRs were identified by isolation of the same bacteria from the bag and the patient's blood or by positive Gram's stain of the bag that confirmed a positive platelet culture. In 1987, a program to minimize PC use in favor of SDP use was initiated as a means of reducing SPTRs. RESULTS: In 12 years, the use of SDPs increased from 51.7 percent to 99.4 percent of all platelet transfusions at one institution. SPTRs fell from three events in 1 year to the current rate of one event per year. The incidence of SPTRs decreased from 1 in 4,818 transfusions to 1 in 15,098 transfusions. The rate of SPTRs due to PCs was 5.39 times higher than that of SPTRs due to SDPs (95% CI, 1.89,12.9). CONCLUSION: The use of SDPs is a simple means of reducing SPTRs. Other measures such as sterilization will be required to eliminate all SPTRs.

The relationship between hemorrhage and low platelet count was first established in patients with acute leukemia, and has been widely applied to thrombocytopenic patients, including BMT patients. Yet, the role of thrombocytopenia in bleeding post BMT has not been systematically studied. We evaluated the risk of bleeding and outcome associated with thrombocytopenia in BMT patients who had prophylactic platelet transfusions at a trigger of 20 x 10(9)/l. Thrombocytopenia was investigated in 321 patients with moderate or severe bleeding (BLD), and in a matched comparison group of 287 patients who did not bleed (NBLD). Profound thrombocytopenia (or = 10 x 10(9)/l) was found in 8.6% of the BLD patients during the week before the bleeding onset, significantly more frequent than in NBLD patients (2.1% to 4%, P0.02), during weeks 2 to 6 post BMT (the period when 75% of the bleeding initiated). On the first day of bleeding, platelet countsor = 10 x 10(9)/l were found in 13.5%, 11-20 x 10(9)/l in 20.4%, and20 x 10(9)/l in 66.1% of all episodes. Overall survival in BLD patients was not associated with the severity of thrombocytopenia before bleeding onset. Severity of thrombocytopenia was significantly associated with reduced survival in NBLD patients. We concluded that bleeding post BMT was significantly associated with thrombocytopenia, but the attributable risk of bleeding from profound thrombocytopenia was not large. Thrombocytopenia may be an important clinical sign in NBLD patients, and should be further explored in relation to acute toxicities other than bleeding.

(1997). Pathological fractures in bone sarcomas. Acta Orthopaedica Scandinavica: Vol. 68, The Scandinavian—Australian Symposium on the Management of Bone and Soft Tissue Sarcomas, pp. 106-107.

The use of peripheral blood progenitor cells (PBPC) for hematopoietic rescue after high-dose chemotherapy is limited by the number of leukaphereses required to collect an adequate number of hematopoietic progenitors. To optimize the collection of PBPC, we evaluated a single large-volume leukapheresis protocol with citrate anticoagulation. A group of 23 patients received cyclophosphamide (4 g/m2) and GM-CSF (5 micrograms/kg/day for 15 days) as PBPC mobilization, with a single outpatient 6 h leukapheresis performed on the COBE Spectra 15 days later. Citrate (0.190 mmol/ml) was infused at 1.2 ml/L of blood/minute with a whole blood to citrate ratio between 17:1 and 25:1. Calcium chloride (50 mM) was administered at a citrate to calcium molar ratio between 10:1 and 5:1 to prevent hypocalcemia. A median 36.6 L (range 24.4-46.4) blood was processed using 338 mM citrate (269-473) and 50 mM calcium (25-75). A median 5 x 10(6) CD34+ cells/kg (0.3-24) and 6.2 x 10(5) CFU-GM/kg (0.001-29) were collected, representing 5.6 and 5.9 more PBPC, respectively, than were in circulation at the initiation of leukapheresis. We conclude that a 6 h large-volume leukapheresis following cyclophosphamide and GM-CSF mobilization is safe, can recruit hematopoietic progenitors into the circulatory compartment, and allows the collection of high numbers of PBPC in a single procedure.

ODAY, blood transfusion is a standard component of medical therapy. Most of the public are aware of its crucial role in the management of trauma, cancer, hemophilia, and other illnesses. The public also participate in transfusion through donation of blood. Hence, transfusion may be perceived as one of the most well-understood aspects of modem medicine. The apparent simplicity of blood transfusion, however, belies its intrinsic complexity. Generally perceived as a single fluid, blood is actually a complex mixture of salts, macromolecules, cells, and cell fragments. The collection, storage, and transfusion of each of these components is complex, as is the determination of benefits and risks of transfusion. Spurred by the concern regarding the acquired immunodeficiency syndrome (AIDS), public interest in controlling the sources of blood for transfusion, as well as determining the indication for its use, has increased. These factors have made the area of blood transfusion an increasingly challenging problem for the blood bank specialist, physician, and nurse. Like the development of oncology itself~ clinical blood transfusion has been a development of the past 100 years. From even the most primitive times, however, blood has been recognized as a life force; uncontrolled blood loss has been temporally associated with death. Reversal of this process and replenishment of life must have been a desire of the earliest men. The first written descriptions of attempts at human transfusion were recorded in 1667 when an Englishman, Richard Lower, and a Frenchman, Jean Batiste Denis, tried to transfuse sheep blood into humans. 1 These initial attempts at transfusion were, of course, unsuccessful. In Denis's case, following initial apparent success, serial transfusions were attempted with subsequent severe reactions. These problems ultimately led to the revocation of the Denis's license and his untimely and rapid departure from Pads. The first human-to-human transfusion was reported by Phillip Physic of Philadelphia. While in Edinborough in 1795, he noted the use of blood transfusion in treating obstetrical hemorrhage. This practice was further popularized in England by James Blundell in the early 1800s. 2 Such early attempts at transfusion were hampered by lack of equipment to transfuse the blood, ignorance of the antigenic barriers of blood types, and lack of recognition of the effect of hypovolemia on the donor. Nonetheless, transfusions were attempted during the Crimean War and the American Civil War. Lacking a clear pattern of success, through the last half of the 19th century physicians experimented with alternate sources of transfusion, including animal blood and milk. The first successful use of normal saline transfusion was reported in 1884. These early transfusion attempts were also hampered by a poor understanding of the concept of shock. It was not until World War I that the relationship between bleeding and shock was appropriately understood. The turn of the century anticipated four events that would determine the course of modem transfusion science. These included definition of blood groups, solutions for the technical problem of indirect transfusion, development of safe anticoagulants, and understanding the role of blood and blood replacement in the pathophysiology of shock. In Table I these events are depicted chronologically relative to major milestones in the development of oncologic and nursing science.

Seventy-four consecutive patients with high-risk acute lymphoblastic leukemia (ALL) were given cyclophosphamide (CY; 50 mg/kg on each of 4 days) plus total body irradiation (TBI; 300 rad on each of 4 days) followed by a human leukocyte antigen (HLA)-identical allogeneic bone marrow transplant (BMT). Eighteen patients in first complete remission (CR1), 36 in CR2, 16 in CR3, and four in CR4 were transplanted. Patients in CR1 were transplanted 1 to 8 months (median, 3 months) after attaining CR. All 18 patients in CR1 had one or more poor risk factors: age more than 18 (N = 17), initial leukocyte count greater than or equal to 20,000 (N = 11), Ph 1 chromosome (N = 2), delay in attaining CR more than 6 weeks (N = 8), or extramedullary disease (N = 1). Of those transplanted in CR2, 72% had relapsed on therapy. The 5-year event-free survival (EFS) rates for patients transplanted in CR1, CR2, and CR3 are 42%, 43%, and 25%, respectively, at median follow-up times of 57, 54, and 72 months, respectively. Children aged less than 18 years transplanted in CR2 have a 5-year EFS rate of 54%. All CR4 patients died early after transplant. The actuarial probability of relapse is 20%, 26%, and 48% for those transplanted in CR1, CR2, and CR3, respectively. Although there was substantial transplant-associated mortality, it decreased over the decade of the study (P = .01). This study indicates that BMT offers an attractive alternative to postremission chemotherapy in patients in CR1 with poor prognostic factors and in patients in second remission.

In Reply. —We wish to thank Dr Ciavarella for the interesting points that have been raised. If one calculates the rate of contamination of a single unit of platelets, the contamination rate is indeed one per 13460 events. However, from a clinical point of view, the number of events per transfusion is the most important incidence. Hence, we chose this measure (one per 4200 transfusions) in our presentation. We also hope that a method of rapid diagnosis could be developed. Lacking an effective alternative, we continue our practice of saving an aliquot of each unit. We feel that it is a relatively inexpensive procedure that can supply definitive information in a short period of time. It also allows us to determine if the contamination is occurring due to events at the time of collection or to pooling. We have not explored the possibility of using monoclonal antibodies for rapid antigen

Objective. —To determine the medical and laboratory characteristics of bacteremia secondary to transfusion of microbiologically contaminated platelet concentrates. Design. —Febrile transfusion reactions were prospectively monitored over 42 months. Units involved in reactions were evaluated with Gram's stain and culture tests. Setting. —Comprehensive cancer center. Patients. —Patients receiving platelet transfusions for thrombocytopenia secondary to bone marrow failure. Result. —Seven cases of transfusion-associated sepsis were observed. Multidonor platelet products stored for 5 days resulted in an incidence of sepsis five times higher than those stored for 4 days or less ( P Conclusions. —Contamination of platelet concentrates remains a significant clinical problem. Septic episodes may be reduced by transfusion of platelets with shorter storage intervals. ( JAMA . 1991;266:555-558)

Review of 235 consecutive patients undergoing bone marrow transplantation was performed in order to define the clinical syndrome of venoocclusive disease of the liver (VOD) in these patients. Analysis of all patients with histologically proven VOD revealed a consistent clinical syndrome of liver dysfunction occurring within the first 3 weeks after marrow infusion. This was characterized by hyperbilirubinemia peaking at greater than or equal to 2 mg/dl with at least 2 of 3 other findings: hepatomegaly, ascites, and 5% or greater weight gain. VOD developed in 22% (52 of 235). A persistently elevated aspartate aminotransferase (SGOT) prior to transplant was associated with an increased risk of developing VOD by multivariate analysis (P = 0.0003), and acute leukemia in first remission was associated with a decreased risk (P = 0.02). Neither the preparative regimen (busulfan and cyclophosphamide versus cyclophosphamide and total body irradiation) nor the type of graft (allogeneic versus autologous) influenced the occurrence. Twenty-four of these 52 patients (47%) died with VOD (10% of the entire group). This makes VOD the third leading cause of death in our allogeneic graft recipients, and the second leading cause in our patients receiving autologous transplants. VOD is a common complication of bone marrow transplantation and has a specific clinical presentation, which usually allows diagnosis without the need of liver biopsy.

The results of therapy with carbenicillin plus trimethoprim-sulfamethoxazole (C-T/S) were compared to those obtained with carbenicillin plus gentamicin (C-G) in a prospective double-blind study of empiric antibiotic therapy in granulocytopenic patients. Patients were stratified into two groups: favorable-prognosis, group 1 (carcinoma, lymphoma, multiple myeloma), or unfavorable-prognosis, group 2 (acute leukemia, bone marrow transplantation), based on anticipated duration of granulocytopenia. Over-all, empiric antibiotic trials were more often successful (P = 0.004) in group 1 (55 of 62 patients or 89 per cent) than in group 2 (42 of 64 patients, 66 per cent). Within group 1, there was a favorable outcome in 30 of 32 (94 per cent) C-T/S trials and in 25 of 30 (83 per cent) C-G trials (P = 0.25); within group 2, there was a favorable outcome in 23 of 30 (77 per cent) C-T/S trials and in 19 of 34 (56 per cent) C-G trials (P = 0.14). Combined results in both groups indicated a higher proportion of favorable outcome in C-T/S trials (53 of 62, 85 per cent) than in C-G trials (44 of 64, 69 per cent). Further analysis (Mantel-Haenszel test) showed the over-all difference in outcome to be significant (P = 0.049), but the general applicability of this result may be limited by the rather low incidence of gram-negative bacterial infections in this study. There was no difference between the treatment regimens in antibiotic toxicity, and serious superinfection occurred only in group 2 patients (21 per cent of trials), equally divided between treatment arms. Initial protocol dosing achieved target plasma levels of trimethoprim (3 to 8 μg/ml) or gentamicin (4 to 10 μg/ml) in 57 of 68 (84 per cent) C-T/S trials compared to 21 of 60 (35 per cent) C-G trials.

Ninety-nine patients with acute nonlymphocytic leukemia (ANLL) received HLA-identical bone marrow transplants (BMTs) from sibling donors after preparation with high doses of busulfan and cyclophosphamide. Forty- nine patients were transplanted in first complete remission (CR), and 50 patients were transplanted in second and third CR and early relapse. Fifty-three received one of three regimens containing primarily low- dose cyclophosphamide (group I) for graft-v-host disease (GVHD) prophylaxis; since March 1983, 46 patients received intravenous (IV) cyclosporine (group II). After December 1983, only cytomegalovirus (CMV)-seronegative blood products were used in appropriate patients, and since April 1984 patients seropositive for herpes-simplex virus (HSV) and CMV received high-dose acyclovir prophylaxis. For patients transplanted in first CR, there was a significantly lower incidence of acute GVHD (P = .005) and deaths related to GVHD and interstitial pneumonitis (P = .001) in patients in group II. This was reflected in an improved Kaplan-Meier probability of disease-free survival (DFS) in the 22 patients transplanted in group II as compared with the 27 patients in group I (64% +/- 10% v 30% +/- 9%, P = .017). The probability of remaining in remission was slightly lower in group II (82% +/- 9% v 94% +/- 6%, P = .479). For patients transplanted in second and third CR and early relapse, the incidence of acute GVHD (P = .026) and deaths related to GVHD and interstitial pneumonitis was significantly lower in group II (P = .029); the probability of remaining in remission was also less (47% +/- 15% v 91% +/- 15%, P = .022). However, the probability of DFS was not significantly different between the two groups (26% +/- 10% v 35% +/- 18%, P = .957). We conclude that transplantation for patients in first CR who received IV cyclosporine therapy is effective treatment; patients with more refractory disease treated with the same cyclosporine regimen (group II) had a lower incidence of GVHD than those treated in group I, but survival did not improve because of an increase in the number of relapses and other nonleukemic complications.

A 58-year-old man developed recurrent episodes of symmetrical motor weakness associated with acroparesthesias and areflexia. The cerebrospinal fluid protein was elevated and nerve conduction velocities were slowed. There was no evidence of systemic disease or toxic exposure, and a diagnosis of chronic relapsing inflammatory polyradiculoneuropathy was made. The patient improved during treatment with corticosteroids, but steroid-induced complications necessitated discontinuance. A recrudescence of symptoms prompted a search for alternative therapy, and plasma exchange was tried. A marked improvement in strength was noted following each course of plasma exchange, suggesting that further similar trials are justified.

In a series of 100 bone marrow harvests, the incidence of bacterial contamination of the bone marrow graft was 17 percent. Ex vivo manipulation of some of the grafts prior to infusion may have caused additional bacterial contamination. All isolated bacteria were common skin flora, and no serious sequelae were observed in the patients receiving the culture-positive bone marrow grafts. Samples of harvested bone marrows purposely contaminated with an isolate of Staphylococcus epidermidis demonstrated a bactericidal property that was maximal early after bone marrow collection. Bone marrow collection and ex vivo manipulation may result in considerable bacterial contamination. Procedures must be developed to assure that marrow collection and processing do not result in clinically significant contamination.

Since 1980, adults with acute myelocytic leukemia (AML) have been treated on two clinical studies using intensive timed sequential therapy. All patients ages 16 to 80, including those with secondary AML (SAML) and those with AML preceded by a hematologic disorder (AHD), were treated, regardless of medical complications at the time of diagnosis. The first study combined high doses of cytarabine (ara-C, AC) and daunorubicin (DRN, D) in sequence (Ac2-D-Ac) and resulted in a complete remission rate of 55%. A group of these patients selected by functional status was able to receive a second course of therapy in remission, which resulted in a disease-free survival (DFS) of greater than 40% at 7 years. Because of toxicity in that study, 114 patients were entered on a second trial initiated 4 years ago, using a less aggressive first course, with amsacrine, to achieve a stable remission (Ac2-D-Amsa). This first treatment was followed by a more intensive second course (Ac6-D-Ac). With this two-step approach, a higher complete remission (CR) rate (76% for de novo AML and 54% for SAML-AHD) was achieved, and more patients were able to receive the second course of therapy. At the current median follow-up of 26 months, the median duration of DFS and overall survival are 11 and 14 months for patients with de novo AML. Age less than or equal to 55 is the most significant prognostic factor for both prolonged DFS and overall survival, with median durations of 17 and 18 months, respectively, for these younger patients. Patients with SAML-AHD remain relatively refractory to treatment despite aggressive chemotherapy, with median durations of DFS and overall survival of 9 months and 5 months, respectively.

This phase I study was conducted to determine the maximal safe concentration of 4-hydroperoxycyclophosphamide (4HC) that could be used for in vitro treatment of bone marrow from patients with acute leukemia undergoing autologous bone marrow transplantation. Concentrations of 40 to 120 micrograms/mL of 4HC were used in 30 patients with relapsed or high-risk acute leukemia and in six patients with nonleukemic malignancies. All patients received marrow-lethal cytoreductive therapy followed by infusion of the 4HC-treated marrow. Complete inhibition of granulocyte and macrophage colony-forming cells was obtained at 80 micrograms/mL. Nevertheless, only one transplant-related death and otherwise full hematologic recovery was observed at concentrations of 4HC up to 100 micrograms/mL. At 120 micrograms/mL, there were three transplant-related deaths, including two of the three patients who required the infusion of reserve marrow. Among the acute leukemia patients, three remain in complete remission at 1,337, 1,017, and 967 days after transplant. Among the nonleukemic patients, two remain in complete remission at 1,081 and 1,017 days after transplant. At the maximum safe concentration of 4HC (100 micrograms/mL), satisfactory hematologic recovery can be obtained, despite elimination of detectable hematopoietic progenitors.

Interstitial pneumonitis (IP) occurred in 20 of 143 (14%) patients who received cytoreductive therapy followed by autologous bone marrow transplantation (BMT) as treatment for malignancy. IP occurred at a median onset time of 41 days (5 to 624 days). All but three of the episodes were fatal. Of the thirteen cases in which tissue was examined, half were idiopathic; the remainder were due to various infectious agents. The actuarial incidences of idiopathic (7%) and CMV IP (2%) in these marrow autograft recipients were lower than the incidences of idiopathic (19%) and CMV IP (17%) in comparably treated recipients of allogeneic BMT (P less than or equal to 0.001 for both comparisons).

Busulfan is an alkylating agent that is widely used in preparative regimens for bone marrow transplantation (BMT). We developed a high-performance liquid chromatographic (HPLC) assay for the determination of plasma busulfan concentrations in 30 patients who received oral doses of 1 mg/kg. Concentrations were fit by a one-compartment pharmacokinetic model with first-order absorption. The pattern of absorption and elimination varied widely between patients, with peak concentrations ranging from 1.2 to 10.4 mumol/l (mean, 4.25 +/- 2.49). The elimination half-life ranged from 58 to 433 min (harmonic mean, 140 min). The AUC contributed by a single oral dose ranged from 606 to 5,144 mumol-min/l (mean, 2,012 +/- 1,223). Patients were evaluated for the development of veno-occlusive disease (VOD), a treatment complication that occurs in 20% of patients undergoing BMT and causes 10% of transplantation-related deaths. All six patients who developed VOD had an AUC greater than the mean, and five of them had an AUC that was greater than 1 SD above the mean. The occurrence of VOD was highly correlated with an increased AUC (greater than 1 SD above the mean) (X2 = 18; P less than 0.0001). Using multivariate logistic regression, no other statistically significant pharmacokinetic predictor of VOD was found. The tenfold variability in the busulfan AUC and the statistical association of increased AUC with the development of VOD suggest a possible role for therapeutic monitoring in this setting.

Allogeneic bone marrow transplants (BMT) in acute lymphoblastic leukemia following cyclophosphamide (Cy) and total body irradiation (TBI) has resulted in disease-free survival (DFS) for CR1, CR2, and CR3 of 10/18 (56%), 16/30 (53%) and 4/17 (24%), respectively. Median follow-up of survivors was 25-43 months. One relapse was seen in CR1, 1 in CR2, and 6 in CR3. Allogeneic BMT in acute nonlymphoblastic leukemia (ANLL) following busulfan (Bu) resulted in DFS for CR1, CR2 + CR3 + early relapse of 21/47 (45%) and 13/41 (32%), respectively. Median DFS of survivors of all groups together was 36 months. DFS of all patients 20 years or less was 15/27 (56%) and 19/61 (31%) for ages 21-46. Three relapses of 47 (6%) were seen in CR1 and 6/41 (15%) in subsequent remission and early relapse. BMT of autologous BMT with 4-hydroperoxy-cyclophosphamide (4-HC) purged marrow in ANLL in CR1 (5), CR2 (32) and CR3 (9) following Bu + Cy resulted in DFS of 19/46 (41%) for 1-67 months (median 15 months). Twenty patients with prior risk non-Hodgkin's lymphoma received 4-HC-purged marrow following Cy + TBI. DFS was 10/20 (50%) for 1.4-9.5 years (median 2.9 years).

We studied 25 patients with acute nonlymphocytic leukemia in second remission (20 patients) or third remission (5 patients) in whom autologous bone marrow transplantation was performed with use of marrow incubated ex vivo with the alkylating agent 4-hydroperoxycyclophosphamide. Patients received intensive cytoreductive therapy with busulfan and cyclophosphamide or cyclophosphamide and total body irradiation, followed by an infusion of marrow that had been collected in remission, treated with 4-hydroperoxycyclophosphamide, and cryopreserved. Four patients died from bacterial or fungal sepsis within the first month after transplantation, and one patient with persistent marrow hypoplasia died from gram-negative sepsis 155 days after infusion with autologous marrow. In the remaining patients, peripheral-blood levels of neutrophils in excess of 0.5 X 10(9) per liter and platelet counts over 50 X 10(9) per liter were attained at median intervals of 29 and 57 days after transplantation, respectively. Nine patients had leukemic relapses at 73 to 316 days (median, 182 days) after infusion of autologous marrow, for an actuarial relapse rate of 46 percent. Eleven patients (eight in second remission and three in third) remained in remission at a median of more than 400 days (range, greater than 230 to greater than 1653 days) after transplantation. The observed disease-free survival after transplantation with autologous marrow treated with 4-hydroperoxycyclophosphamide compares favorably with the results of syngeneic or allogeneic transplantation in similar groups of patients.

During a study of the effect of plasma exchange on glycosphingolipid metabolism, a patient with Fabry's disease noted a dramatic improvement in his painful acroparesthesia. A controlled study was therefore undertaken. Observations were made of nerve conduction times, graded exercise testing, and psychometric evaluations during and after two planned series of three plasma exchanges: one a true plasma exchange and the other a "sham' control in which the patient received his own plasma. All observers and the patient were blinded and unanimously attributed beneficial results to the sham procedure. This study demonstrates the need for controlled studies in diseases prone to unpredictable exacerbation or spontaneous remission and outlines one possible technique of controlling studies involving plasma exchange.

Fifty-one patients with acute nonlymphocytic leukemia (16 with end-stage disease, 17 in second or third remission or in early relapse, and 18 in first remission) were given infusions of HLA-identical sibling marrow after cytoreduction with high doses of busulfan and cyclophosphamide. Actuarial two-year survival rates were 0 per cent, 29 per cent, and 44 per cent, respectively. Twelve patients are still alive and in remission after 327 to 1488 days, with 10 surviving beyond two years. Acute graft-versus-host disease and viral pneumonia were the major causes of death. Leukemic cells failed to clear in one patient with end-stage disease, and a relapse with meningeal leukemia occurred in another. Only one other relapse was seen--in a patient given a transplant during a third remission. Survival was favorably affected by younger age and transplantation during first remission. We conclude that high-dose chemotherapy with busulfan and cyclophosphamide, followed by allogeneic-marrow transplantation, can produce long-term remission of acute leukemia. Chemotherapy with high-dose busulfan and cyclophosphamide before transplantation provides an effective alternative to cyclophosphamide and total-body irradiation before transplantation for the treatment of acute nonlymphocytic leukemia.

To determine the predictive value of a radiolabeled antiglobulin test for platelet crossmatching to select platelets for transfusion, we evaluated 230 transfusions in 42 alloimmunized oncology patients. Transfusions were classified according to the degree of HLA match. The value of the crossmatch in predicting platelet transfusion outcome was analyzed for each HLA category. For predicting the 1-hour corrected platelet count increment of all transfusions, the sensitivity of the test was 86 percent, specificity 84 percent, and total predictive value 84 percent. The crossmatch technique had similar predictive ability in all categories of HLA match, whether analyzing the results on the basis of the 1- or 24-hour platelet count rise.