Search

Background: Approximately 600,000 total knee arthroplasties (TKA) are performed every year in the United States and the number of procedures has increased substantially every year. These demands may further strain the government, insurers, and patients struggling with increasing healthcare spending. A delay in proceeding to surgery after hospital admission may affect the overall healthcare costs. To our knowledge, the current literature has not addressed the incidence of, and preoperative risk factors for, a surgical delay in TKA., Methods: The ACS-NSQIP 2011 database was reviewed to identify patients undergoing elective primary total knee arthroplasty (TKA) using the Current Procedural Terminology (CPT) code 27447. 14,881 cases were no delay in proceeding to surgery after hospital admission while 139 cases were delayed for TKA. Risk factors or comorbidities contributing to surgical delay in TKA were identified. A univariate analysis of all patient parameters was conducted to measure the difference between the two cohorts. Finally, a multivariate logistic regression analysis was then conducted to identify risk factors or comorbidities for surgical delay., Results: There were 139 cases of surgical delay in TKA (0.93%). Congestive heart failure (P = 0.017), bleeding disorder (P <0.0001), sepsis (P <0.0001), a prior operation in the past 30 days (P <0.0001), dependent functional status (P <0.0001), ASA class 3 (P = 0.046), and hematocrit <38% (P <0.0001) were independent risk factors for a surgical delay. Postoperative medical complication (2.2% vs 0.8%, P < 0.0001) in surgical delay was significantly higher than non-delayed cohort., Conclusion: The optimization of preoperative modifiable risk factors appears to be one of the best strategies to reduce delayed surgery and therefore costs in TKA., (Copyright © 2015. Published by Elsevier Inc.)

Purpose: To kinematically and biomechanically compare 4 different types of tibial tunnel management in single-stage anterior cruciate ligament (ACL) revision reconstruction with the control: primary ACL reconstruction using a robotic-based knee testing setup., Methods: Porcine knees and flexor tendons were used. One hundred specimens were randomly assigned to 5 testing groups: (1) open tibial tunnel, (2) bone plug technique, (3) biodegradable interference screw, (4) dilatation technique, and (5) primary ACL reconstruction. A robotic/universal force-moment sensor testing system was used to simulate the KT-1000 (MEDmetric, San Diego, CA) and pivot-shift tests. Cyclic loading and load-to-failure testing were performed., Results: Anterior tibial translation increased significantly with all of the techniques compared with the intact ACL (P < .05). In the simulated KT-1000 test, groups 2 and 3 achieved results equal to those of primary ACL reconstruction (P > .05). The open tunnel and dilated tunnel techniques showed significantly greater anterior tibial translation (P < .05). The results of the simulated pivot-shift test were in accordance with those of the KT-1000 test. No significant differences could be observed regarding stiffness or maximum load to failure. However, elongation was significantly lower in the primary ACL reconstruction group compared with groups 1 and 3 (P = .02 and P = .03, respectively)., Conclusions: Filling an incomplete and incorrect tibial tunnel with a press-fit bone plug or a biodegradable interference screw in a standardized laboratory situation provided initial biomechanical properties and knee stability comparable with those of primary ACL reconstruction. In contrast, the dilatation technique or leaving the malplaced tunnel open did not restore knee kinematics adequately in this model. Backup extracortical fixation should be considered because the load to failure depends on the extracortical fixation when an undersized interference screw is used for aperture fixation., Clinical Relevance: Our biomechanical results could help orthopaedic surgeons to optimize the results of primary ACL revision with incomplete, incorrect tunnel placement., (Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Purpose: To overview the complications involving extensor apparatus of the knee following total knee arthroplasty (TKA) and to summarize which are the lines of treatment available and their reported outcomes in literature., Methods: A comprehensive search of several databases was performed using as basic keywords "complications after TKA", "extensor mechanism disruption", "periprosthetic patellar fracture", "quadriceps tendon rupture", "quadriceps tendon rupture" isolated or combined with other terms by using Boolean operators. The methodological quality of each article was also evaluated using the Coleman methodology score (CMS)., Results: Twenty-nine studies were evaluated. The mean CMS of the studies selected was 33.1/100. Patellar fractures, requiring surgical treatment when there is rupture of the extensor mechanism or loosening of the patellar component, were treated surgically in 28.1 % of patients. The patellar and quadriceps tendon ruptures were surgically treated with reconstruction or augmented repair, respectively, in 98.6 and 76.5 %., Conclusion: Complications involving the extensor apparatus of the knee following a TKA need early and appropriate management to avoid their devastating influence on joint functionality. Management has to be evaluated very carefully based on the site of the lesion, integrity of the prosthetic components and surrounding tissue to restore, and the patients' individual characteristics. The surgical approach for comminuted periprosthetic fractures and reconstruction of torn tendons of the extensor apparatus are needed to restore function and decrease pain, but, given the poor methodological quality of the studies published so far, it is not clear which surgical technique or graft leads to better outcomes. Therefore, there is an absolute need for better designed comparative trials producing clearer and stronger evidence on this critical matter., Level of Evidence: IV.

Background: Transplantation of osteochondral allografts (OCAs) freshly preserved for ≥30 days has proven to be a reliable technique for cartilage resurfacing. However, the prolonged storage of allografts comes at the expense of chondrocyte viability, which declines precipitously after 14 days under refrigeration. Despite this, radiographic data indicate that most allograft cartilage remains stable for years after implantation. The apparent durability of partially devitalized cartilage begs the question of how the extracellular matrix is maintained., Hypothesis: Compared with patients' defect cartilage, replacement OCAs freshly preserved for 36 days on average contain significantly lower levels of cartilage matrix-destructive metalloproteinases, which may contribute to the long-term stability of implanted grafts., Study Design: Descriptive laboratory study., Methods: Chondrocyte density was determined by the cell yield from digested cartilage and by double-strand DNA content quantified with PicoGreen assay. Chondrocyte viability was estimated by staining enzymatically isolated chondrocytes with calcein AM and ethidium homodimer-2. Cartilage proteoglycan (PG) content was analyzed with dimethylmethylene blue assay. The in vitro 48-hour release of PG-depleting metalloproteinases including matrix metalloproteinase (MMP)-1, -3, -13, and ADAMTS-5 from cartilage was examined with Western blotting. The data were compared between diseased cartilage from patients and samples from matched grafts. The relative amount of MMP-3 to its endogenous inhibitor, tissue inhibitor of MMP-1 (TIMP-1), was also determined with Western blotting., Results: Chondrocyte density decreased linearly with allograft storage time and declined by an average of 43%. PG content decreased while the percentage of nonviable chondrocytes increased with storage time, with the former showing less linearity. However, PG content remained in the normal range and was significantly higher than that in patients' defect cartilage. Correspondingly, significantly less PG-depleting metalloproteinases and a much lower MMP-3/TIMP-1 ratio were detected in allograft cartilage than in patients' diseased cartilage., Conclusion: These findings indicated that, at the time of implantation, fresh-preserved OCAs contained significantly lower levels of PG-depleting metalloproteinases compared with patients' defect cartilage, which might contribute to their long-term stability in vivo., Clinical Relevance: The comparatively low expression of cartilage-dissolving metalloproteinases in human OCAs freshly preserved over 30 days offers support to the long-term durability of implanted grafts. Based on study data that showed similarity in the response to inflammatory cytokines between patients' cartilage and OCA cartilage, strategies that can alleviate inflammation may provide extra benefit for the survival of implanted grafts. In terms of the practice of graft preservation, agents that can keep balance between the ATP supply and demand or stabilize the cell membrane or inhibit the activation of metalloproteinases may significantly improve cell viability in fresh-preserved OCAs with a storage time longer than 5 weeks., (© 2015 The Author(s).)

Purpose: In this prospective case control study, the effectiveness of surgical management of irreparable rotator cuff tears in terms of patient's status and quality of life was evaluated in two groups of patients: one group receiving arthroscopic debridement associated with acromioplasty and bursectomy and the other receiving an arthroscopic partial repair of the rotator cuff tear., Methods: Sixty-eight patients (47 males and 21 females) undergoing arthroscopic shoulder surgery for massive irreparable rotator cuff tear were enrolled in our study. Patients were divided into two groups: Group AP (debridement associated with acromioplasty and bursectomy) and Group PR (partial repair). Pre- and post-operative range of motion (ROM), modified-UCLA shoulder score and strength measurement were performed. The RC-QOL was used at the time of the last follow-up to assess patients' perception of their quality of life., Results: The final follow-up was 7.8 (±2.3, range 5-9) years. ROM measures were significantly increased from pre- to post-operative evaluations, with significant intergroup differences (P < 0.001). The overall modified-UCLA shoulder score showed a mean pre-operative value of 7.6 ± 2.6 (95 % CI 6.7-8.5) for Group AP and 8.6 ± 4.1 (95 % CI 7.0-9.9) (n.s.) for Group PR. The post-operative values at the latest follow-up showed a statistically significant improvement in both groups [21.4 ± 3.7 (95 % CI 20.1-22.7) for Group AP and 28.8 ± 4.2 (95 % CI 27.3-30.2) for Group PR] (P < 0.0001), with a significant intergroup difference (P < 0.0001). The RC-QOL demonstrated a statistically significant difference between the groups [Group AP: 61.8 ± 6.1(95 % CI 59.6-63.9); Group PR: 71.2 ± 9.8 (95 % CI 67.7-74.6)] (P < 0.0002)., Conclusion: Both techniques are effective in reducing patients' symptoms, with higher functional outcomes for partial repair. However, the choice of which technique to undertake should take into account the patients' features concerning the acromio-humeral interval and levels of daily activities., Level of Evidence: Therapeutic case-control study, Level III.

Background: High tibial osteotomy (HTO) is a well-established and commonly utilized technique in medial knee osteoarthritis secondary to varus malalignment. Accurate measurement of the preoperative limb alignment, and the amount of correction required are essential when planning limb realignment surgery. The hip-knee-ankle angle (HKA) measured on a full length weightbearing (FLWB) X-ray in the standing position is considered the gold standard, since it allows for reliable and accurate measurement of the mechanical axis of the whole lower extremity. In general practice, alignment is often evaluated on standard anteroposterior weightbearing (APWB) X-rays, as the angle between the femur and tibial anatomic axis (TFa). It is, therefore, of value to establish if measuring the anatomical axis from limited APWB is an effective measure of knee alignment especially in patients undergoing osteotomy about the knee., Methods: Three independent observers measured preoperative and postoperative FTa with standard method (FTa1) and with circles method (FTa2) on APWB X-ray and the HKA on FLWB X-ray at three different time-points separated by a two-week period. Intra-observer and inter-observer reliabilities and the comparison and relationship between anatomical and mechanical alignment were calculated., Results: Intra- and interclass coefficients for all the three methods indicated excellent reliability, having all the values above 0.80. Using the mean of paired t-student test, the comparison of HKA versus TFa1 and TFa2 showed a statistically significant difference (p<.0001) both for the pre-operative and post-operative sets of values. The correlation between the HKA and FTal was found poor for the preoperative set (R=0.26) and fair for the postoperative one (R=0.53), while the new circles method showed a higher correlation in both the preoperative (R=0.71) and postoperative sets (R=0.79)., Conclusions: Intra-observer reliability was high for HKA, FTal and FTa2 on APWB x-rays in the pre- and post-operative setting. Inter-rater reliability was higher for HKA and TFa2 compared to FTal. The femoro-tibial angle as measured on APWB with the traditional method (FTal) has a weak correlation with the HKA, and based on these findings, should not be used in everyday practice. The FTa2 showed better correlation with the HKA, although not excellent., Level of Evidence: Level III, Retrospective study.

Background: Since it was developed, hip arthroscopy has become the favored treatment for femoroacetabular impingement. Due to recent considerable improvements, the indications for this technique have been widely extended. Injuries of the rectus femoris tendon origin, after an acute phase, could result in a chronic tendinopathy with calcium hydroxyapatite crystal deposition, leading to pain and loss of function. Traditionally, this condition is addressed by local injection of anesthetic and corticosteroids or, when conservative measures fail, by open excision of the calcific lesion by an anterior approach., Purpose: To assess whether arthroscopic excision of calcification of the proximal rectus is a safe and effective treatment., Study Design: Case series; Level of evidence, 4., Methods: Outcomes were studied from 6 top amateur athletes (age range, 30-43 years; mean, 32.6 years) affected by calcification of the proximal rectus who underwent arthroscopic excision of the calcification. Patients were preoperatively assessed radiographically, and diagnosis was confirmed by a 3-dimensional computed tomography scan. To evaluate the outcome, standardized hip rating scores were used pre- and postoperatively (at 6 and 12 months): the Hip disability and Osteoarthritis Outcome Score, Oxford Hip Score, and Modified Harris Hip Score. Moreover, visual analog scales (VAS) for pain, sport activity level (SAL), and activities of daily living (ADL) were also used., Results: One year after surgery, all patients reported satisfactory outcomes, with 3 of 6 rating their return-to-sport level as high as preinjury level, and the remaining 3 with a percentage higher than 80%. Five patients ranked their ability to carry on daily activities at 100%. Statistical analysis showed significant improvement of the Oxford Hip Score, the Modified Harris Hip Score, and all 3 VAS subscales (pain, SAL, and ADL) from pre- to latest postoperative assessment (P < .05)., Conclusion: Arthroscopic excision of rectus femoris tendon calcification yields satisfying results with few risks to the patient as well as rapid recovery., Clinical Relevance: The recent improvements in hip arthroscopy give the opportunity to address an increasing number of hip conditions effectively and safely, with rapid recovery for the patient. Arthroscopic excision of rectus femoris tendon calcification can be considered a feasible option, with few risks to the patient, rapid recovery, and satisfying outcomes.

Background: Approximately 100,000 anterior cruciate ligament (ACL) reconstructions are performed in the USA each year. Interference screw fixation is considered the standard for rigid fixation of the graft and provides higher fixation strength compared with other devices such as staples or buttons. The present study summarizes the latest evidence comparing the effectiveness of the available classes of interference screws for fixation of ACL grafts., Sources: A comprehensive search of the CINAHL, PubMed, Google Scholar, Embase Biomedical databases and the Cochrane Central Registry of Controlled Trials was performed in March 2013. Twelve studies met our inclusion criteria., Areas of Agreement: Most studies showed no intergroup difference in terms of outcomes measured with validated clinical scores such as IKDC (International Knee Documentation Committee), Lysholm score and Tegner activity level. There was no significant difference regarding range of motion. Knee stability as evaluated with pivot shift and KT arthrometer showed a significant difference only in one study, favouring metallic interference screws. Tunnel widening is much more evident and marked patients who underwent ACL reconstruction with bioabsorbable screws, with no influence on the final clinical results achieved. Complication rates between the two screw classes were similar. The average modified Coleman methodology score was 74.67. AREAS OF UNCERTAINTY/RESEARCH NEED: The data comparing the outcomes achieved by two different materials for fixation, bioabsorbable and metallic, to be used during single-bundle ACL reconstruction, showed no significant difference in the final patient outcomes, in terms of clinical scores, clinical evaluation and imaging.

Purpose: To compare two groups of patients who underwent two different arthroscopic procedures for repair of articular-sided partial-thickness rotator cuff tears (PTRCTs)., Materials: This is a comparative prospective study of two methods for repair of partial cuff tears: Thirty-two patients underwent arthroscopic rotator cuff repair with a transtendon technique (group 1); 28 underwent arthroscopic full-thickness conversion and repair of the lesion (group 2). ROM measures, clinical findings, MRI features (tendon healing and re-tear), Constant-Murley and ASES scores were assessed pre- and postoperatively and compared. Patients were also asked about return to sport and level of activity., Results: At the last appointment, patients of both the groups were significantly improved for clinical findings, ROM measures, imaging features, Constant-Murley and ASES scores than at baseline, without any significant inter-group difference. In group 1, 15 of 20 patients (75 %) who practiced recreational sport activities had returned to sport at the same level as before the onset of symptoms, without any discomfort. In group 2, 12 of 18 patients (67 %) had returned to the same level of sport activity they practiced before symptoms. At the last follow up, MRI showed rotator cuff healing in 31 patients of Group 1 and 27 patients of Group 2 (p = 0.83)., Conclusions: The two procedures are safe, effective, and comparable.

Introduction: Following knee surgery, rehabilitation can dramatically affect the postoperative course and the final outcomes of the procedure. We systematically reviewed the current literature comparing clinical outcomes of home-based and outpatient supervised rehabilitation protocols following knee surgery., Sources of Data: We searched Medline, CINAHL, Embase, Google Scholar, The Cochrane Library and SPORTDiscus. The reference lists of the previously selected articles were then examined by hand. Only studies comparing clinical outcomes of patients who had undergone knee surgery followed by different rehabilitation programs were selected. Then the methodological quality of each article was evaluated using the Coleman methodology score (CMS), a 10-criterion scoring list assessing the methodological quality of the selected studies., Areas of Agreement: Eighteen studies were evaluated in the present review. Three were retrospective studies. The remaining 15 studies were prospective randomized clinical trials. The supervised and home-based protocols did not show an overall significant difference in the outcomes achieved within the studies reviewed. The mean CMS was 77.2., Areas of Controversy: The heterogeneity of the rehabilitation protocols used in the studies reviewed makes it difficult to draw definite conclusion on the subject., Growing Points: Supervision and location does not seem to directly determine the final outcomes. Numerous variables, including comorbidities and motivation, could influence the results and deserve to be accounted for in future investigations., Research: Better designed studies are needed to show a clear superiority of one rehabilitation approach over another and its applicability to the various surgical procedures involving the knee.

Objectives: We critically review the existing studies comparing the features of single- and double-row repair, and discuss suggestions about the surgical indications for the two repair techniques., Data Sources: All currently available studies comparing the biomechanical, clinical and the biological features of single and double row., Main Results: Biomechanically, the double-row repair has greater performances in terms of higher initial fixation strength, greater footprint coverage, improved contact area and pressure, decreased gap formation, and higher load to failure. Results of clinical studies demonstrate no significantly better outcomes for double-row compared to single-row repair. Better results are achieved by double-row repair for larger lesions (tear size 2.5-3.5 cm)., Conclusions: Considering the lack of statistically significant differences between the two techniques and that the double row is a high cost and a high surgical skill-dependent technique, we suggest using the double-row technique only in strictly selected patients., (Copyright © 2012 S. Karger AG, Basel.)

Arthroscopic surgery has become the most popular treatment to repair rotator cuff tears. Although the exact prevalence of postoperative stiffness is unknown, many studies report an incidence rate of 4% to 15%. Management of postoperative shoulder stiffness depends on the cause of the stiffness. Nonoperative and operative management modalities are available, but postoperative shoulder stiffness is often resistant to nonsurgical management. When conservative treatment fails, surgical release of the scar tissue and adhesions can be performed both by arthroscopic or open surgery. Arthroscopic capsular release is the preferred technique for capsule contraction and adhesion formation, as it allows precise and selective debridement of the scar tissue and division of the shortened and thickened capsule by partial or extensive capsulectomy.

Ideally, an outcome instrument measures phenomena that are directly relevant to the patient and provides a comprehensive assessment of the impact of a condition on the patient's daily life. During the past decades, several rating scales have been developed to assess the functional status of patients with shoulder pain. Several scoring systems are currently available for the evaluation of patients with rotator cuff pathology. Each of them evaluates shoulder function using specific variables. The main features of these scoring systems are presented in this review. Although many scoring systems are commonly used to evaluate shoulder function, we are still far from a single outcome evaluation system, which is reliable, valid, and sensitive to clinically relevant changes, takes into account both patient's and physician's perspective, and is short and practical to use.

Background: Few data on shoulder arthropathy in patients undergoing arthroscopic repair for glenohumeral instability are available., Hypothesis: Arthroscopic stabilization of Bankart lesions does not prevent the development of postoperative glenohumeral osteoarthritis., Study Design: Case series; Level of evidence, 4., Methods: Clinical (Rowe and Constant scores) and radiographic preoperative and postoperative data from 60 patients who underwent arthroscopic Bankart repair were compared. Osteoarthritis was graded preoperatively and postoperatively with the Buscayret classification grading system. The average age at surgery was 27.6 years, and follow-up averaged 8.0 years., Results: The postoperative incidence of osteoarthritis in patients with no preoperative degenerative changes was 21.8% (12 of 55 patients). The incidence of degenerative joint disease of the glenohumeral joint showed evidence of a statistically significant association with older age at first dislocation and at surgery, increased length of time from the first episode to surgery, increased number of preoperative dislocations, increased length of time from the initial dislocation until surgery, increased number of anchors used at surgery, and more degenerated labrum at surgery. A higher number of preoperative dislocations, a greater length of follow-up, and reduced external rotation in abduction influenced Rowe and Constant scores., Conclusion: The number of anchors used and the state of the labrum are the most important factors associated with a higher risk of radiographic degenerative changes. Longer follow-up investigations are needed to draw meaningful conclusions.

To explore the feasibility and potential advantages of PBSC in allogeneic transplantation, we grafted 24 patients (age 16-57, median 37) with different hematologic diseases (ALL = 10, AML = 5, MM = 4, NHL = 2, CML = 1, MDS = 1, AA = 1), 23 HLA-identical to their siblings and 1 partially matched. Cells were collected from donors by apheresis after G-CSF 10 to 16 mg/kg/day for 4 to 5 days, and stored at 4 degrees C until infusion. The patients were conditioned with chemotherapy regimens including busulfan and cyclophosphamide in the majority of cases and received GVHD prophylaxis with CSA-MTX in all but two. The graft consisted of PBSC alone, with a median of 143.5 (range 18.1-358.9) x 10(4)/kg CFU-GM, 9.0 (range 3.3-18.0) x 10(6)/kg CD34+ cells and 2.8 (range 1.2 to 8.6) x 10(8)/kg CD3+ and cells. An ANC >0.0.5 x 10(9)/L was recovered on (median) day 13 (range 11-17), and a platelet count >50 x 10(9)/L on (median) day 13 (range 12-55) post graft. There was no correlation between CD34+ cells or CFU-GM number in the inoculum and time to hematologic reconstitution. Acute GVHD (grade II-IV) occurred in 10 out of 22 (45%), chronic GVHD in 10 out of 18 evaluable (55%) patients. We found no relationship between occurrence of acute or chronic GVHD and number of CD3+ cells in the graft. Four patients relapsed and 7 died after transplantation. Fifteen patients are currently alive and disease-free 67 to 710 (median 286) days from the graft. Allogeneic transplantation with unmanipulated PBSC ensures a fast and stable engraftment. Acute GVHD incidence and severity seems comparable to that of bone marrow transplantation, but there may be an increase in chronic GVHD, mainly of the extensive form.

Treatment options for acute leukemia relapsing after allogeneic BMT include conventional chemotherapy or a second transplant; however, results are rather discouraging, the first option being associated with poor survival and the second with a high mortality rate. More recently, donor leukocyte infusion (DLI) from the original donor has been used for relapsed patients in an attempt to induce a graft-versus-leukemia (GVL) effect. This procedure is partially devoid of the toxicity inherent to a second BMT. At our Institution, a 36-year-old patient with biphenotypic AML in second complete remission after relapse following allogeneic BMT was treated with peripheral blood stem cell (PBSC)-enriched donor leukocytes, obtained after in vivo priming with rhG-CSF. The patient experienced extensive cGVHD but developed a testicular relapse while in full hematologic remission. After irradiation of the sanctuary site he remains free of disease, still with chronic GVHD, 21 months after bone marrow relapse. This case suggests that immunologically privileged sites are inaccessible to GVHD/GVL effect. This should be considered when planning salvage transplants procedures in patients at risk for extramedullary involvement.

To assess feasibility and potential advantages of PBSC allograft, we transplanted nine patients (age 20-47 years) with advanced or poor-risk hematologic malignancies. These included eight HLA-identical sibling transplants and one partially matched. Cells were collected from donors by apheresis after rh-G-CSF 10-16 micrograms/kg/day for 4-5 days, and stored at 4 degrees C until infusion. Patients were conditioned with busulfan 16 mg/kg and cyclophosphamide 200 mg/kg, and received GVHD prophylaxis with CSA-MTX. The graft consisted of PBSC alone, with a median of 101.2 (range 28-254.2) x 10(4)/kg CFU-GM, 6.84 (range 4.57-15.9) x 10(6)/kg CD34+ cells and 2.5 (range 1.2-6) x 10(8)/kg CD3+ cells. An ANC > 0.5 x 10(9)/1 occurred on (median) day 13 range 11-17), and a platelet count > 50 x 10(9)/l on (median) day 15 (range 12-29) post graft. One patient died of ARDS on day 13, the others are alive 96-485 (median 245) days from the graft. Two patients have relapsed, one of them with isolated CNS involvement. Acute GVHD (grade I-II) occurred in three patients and severe chronic GVHD in six patients, with no relationship to CSA withdrawal. This unexpected incidence of chronic GVHD might be linked to the high number of CD3+ cells in the graft, contributing to a favourable GVL effect.

Experimental and clinical data suggest that Ph-negative myeloid progenitor cells are present, albeit suppressed, in the bone marrow of chronic myeloid leukemia (CML) patients. These residual Ph-negative cells might, in certain circumstances, regain their proliferative advantage over the leukemic Ph-positive clone. Treating CML patients with intensive chemotherapy might allow the harvest, in the early phase of recovery, of Ph-negative stem cells to be used as graft after myeloablative regimen. In our study, 6 CML patients were admitted to a program of autograft with circulating stem cells (CSC) collected after high-dose (5 or 7 g/m2) cyclophosphamide (HD-CY) mobilization. All were autografted, using busulphan 16 mg/kg and melphalan 60 mg/m2. As graft, 4 patients received CSC only, while 2 patients were also given bone marrow, as their peripheral blood CFU-GM yield was unsatisfactory. Two previously alpha-IFN-responding patients showed a slow hematologic recovery, but achieved a marked and further reduction of their Ph-positive metaphases post-graft. Moreover, in one of them, cytogenetic analyses performed on apheresis product showed a more pronounced reduction of his Ph-positive metaphases, as compared to bone marrow samples, suggesting a potential purging effect of the mobilization procedure.

In the present study we assess the antitumor effect and circulating stem cells (CSC) mobilizing capacity of high-dose cyclophosphamide (5 to 7 gr/m2, HDCY). This treatment was given to 21 patients with various hematologic malignancies (8 NHL, 5 MM, 4 HD, 3 CML) excluding 1 with neuroblastoma. All were eligible for later autologous blood stem cell transplantation (ABSCT). To reduce the hematologic toxicity of HDCY, GM CSF was simultaneously administered in 5 patients. HDCY produced a response (as defined by a > 50% reduction of previous tumor mass) in 3 out of 12 HD/NHL and 1 out of 3 MM. Patients with CML were not considered to be evaluable for tumor response. Cell collection yields after HDCY varied widely with a range of 1.5 to 169.9 x 10(4)/Kg (median 13.1) CFU-GM and 1.7 to 18.4 x 10(8)/Kg (median 5.8) MNC collected per patient. Hematologic recovery was rapid and sustained with a median of 16 (12-18) days to PMN > 0.5 x 10(9)/L and 14 (11-18) days to Plt > 100.0 x 10(9)/L. Granulocyte recovery was significantly faster after GM-CSF (13 vs 16 days to PMN > 0.5, p = 0.0008). Non hematologic toxicity consisted mainly of nausea and vomiting, but fatal complications occurred in 2 patients, from pulmonary infection in one and from tumor-lysis syndrome in the other. HDCY represents a useful means of increasing collection of CSC, but toxicity is not irrelevant. Whether a similar anti-tumor effect and mobilizing capacity would be offered by single lower intermediate doses of the drug is still to be ascertained.

A case of localized Trichosporon beigelii infection is reported in a 40-year-old woman with Ph+ chronic granulocyte leukemia who underwent autologous blood stem cell transplantation. On day +14 after autograft, while severely neutropenic, she developed a local infection involving the soft tissues surrounding the central venous catheter (CVC) point of entry into the subclavian vein. Trichosporon beigelii was isolated from culture of the CVC tip; resolution occurred after removal of the CVC, neutrophil recovery and antifungal treatment with amphotericin B and 5-fluorocytosine. To our knowledge this is the first case of CVC localized infection from Trichosporon beigelii after transplantation.

A 53-yr.-old woman with amyloidosis AL was treated with high-dose chemotherapy and autologous stem cell infusion in an attempt to suppress the amyloid secretion. A diagnosis of MGUS had been made six years earlier. During the last year her disease had progressively shifted to a full-blown picture of amyloidosis AL, with renal failure, proteinuria, renal amyloid deposition and plasma cell sheets in the marrow. After an unsuccessful attempt with standard-dose chemotherapy, she received a high-dose regimen of busulphan (14 mg/Kg) and melphalan (40 mg/m2), followed by the infusion of both autologous bone marrow and peripheral blood stem cells. She had full and prompt engraftment, but eight weeks post-graft developed interstitial pneumonitis: CMV was isolated. The patient died while in the intensive care unit. In the literature, this is the first case of amyloidosis AL treated with high-dose therapy and autologous transplantation.

In 8 patients (age 25 +/- 46 years, mean 34.5), 4 with Hodgkin's disease (HD) and 4 with non-Hodgkin's lymphoma (NHL), circulating stem cells (CSC) collected at the time of rapid leukocyte and platelet recovery after intense chemotherapy were employed for autologous hematological reconstitution after very-high-dose chemotherapy (CVB combination). At the time of graft 2 patients were in 1st remission and 2 in 2nd, while the remaining 4 had persistence or progression of disease. Autografted patients received 3.4 +/- 8.3 (mean 5.2) x 10e8/Kg mononuclear cells and 2.1 +/- 40.5 (mean 22.5) x 10e4/Kg CFU-GM. All patients had prompt and sustained engraftment, though in one case platelets never reached normal levels. Recovery time was respectively 10 +/- 17 days (mean 13.2) for granulocytes 0.5 x 10e9/L, and 10 +/- 49 days (mean 20.3) for platelets greater than 50.0 x 10e9/L, with an interval of less than 4 days from greater than 0.5 to greater than 1.0 granulocytes in 7 out of the 8 patients. All patients are currently alive at 57 +/- 645 (median 262) days, and 7 in remission at 61 +/- 645 (median 297) days from autologous blood stem cell transplantation (ABSCT). Our study demonstrates that CSC collected after mobilizing chemotherapy are able to promptly restore and sustain hemopoiesis after marrow ablative chemotherapy in patients with malignant lymphoma. CSC reduce toxicity and hospitalization so impressive, that in malignant lymphomas ABSCT could rapidly be considered for first line strategy.

A 15-year-old boy with non-T ALL in early 2nd remission was autografted using a regimen with busulphan 4 mg/kg/day, po, from day -9 to -6, and cyclophosphamide 50 mg/kg/day, iv, from day -5 to -2. During busulphan administration he experienced a few generalized seizures, and starting on day 25 post ABMT he developed a progressively severe neurological symptomatology characterized by nystagmus, right VIth cranial nerve palsy, truncal ataxia and, finally, confusion and coma. MRI showed lesions in the periaqueductal gray matter, thalamus, mammillary bodies and putamen. Within 24 hours of treatment with thiamine he improved dramatically, but during the following weeks permanent neurologic damage with memory deficit, truncal ataxia and nystagmus became evident. To our knowledge this is the first case of Wernicke's encephalopathy reported after BMT. We suspect in this case a contribution of busulphan to the development of the syndrome.

Autologous peripheral blood stem cells (PBSC) collected after an intensive course of chemotherapy were employed for hematological reconstitution in 3 patients (age 24-44 years), 2 with Hodgkin's and 1 with high-grade non-Hodgkin's lymphoma, in 2nd complete or partial remission. PBSC collections were performed with a Fenwal CS-3000 cell separator (programs "3" and "1-modified"). After collection and partial RBC removal, cells were cryopreserved and stocked in liquid nitrogen. In all patients the CVB combination was employed as myeloablative transplant regimen. Patients received respectively 28.0, 33.1 and 12.3 x 10(4)/Kg peripheral blood CFU.GM. Hematologic recovery was prompt and complete in 2 patients, while a patient with Hodgkin's lymphoma who had previously been treated with combined modality, is still moderately thrombocytopenic and granulocytopenic 148 days post graft. Patients are currently alive and disease-free 148-301 days post graft.

The peripheral blood represents an alternative source of haemopoietic progenitors and permits autografting in patients who have contraindications for a bone marrow harvest but who are otherwise candidates for autologous bone marrow transplantation. Circulating stem cells can be harvested performing several leucaphereses during the overshoot after a mobilization chemotherapy. The use of Fenwal CS-3000 cell separator allows reproducibility from donor to donor and makes the procedure very efficient. We collected peripheral blood stem cells (PBSC) in four patients, 2 with Hodgkin's lymphoma, 1 with high-grade non-Hodgkin's lymphoma and 1 with secondary FAB unclassifiable ANLL: the procedures of collection and cell harvests obtained are reported.