Mesh-based inguinal hernia repairs in an integrated healthcare system and surgeon and hospital volume: a cohort study of 110,808 patients from over a decade.

PURPOSE: The aim of this study was to describe a cohort of patients who underwent inguinal hernia repair within a United States-based integrated healthcare system (IHS) and evaluate the risk for postoperative events by surgeon and hospital volume within each surgical approach, open, laparoscopic, and robotic. METHODS: Patients aged ≥ 18 years who underwent their first inguinal hernia repair were identified for a cohort study (2010-2020). Average annual surgeon and hospital volume were broken into quartiles with the lowest volume quartile as the reference group. Multiple Cox regression evaluated risk for ipsilateral reoperation following repair by volume. All analyses were stratified by surgical approach (open, laparoscopic, and robotic). RESULTS: 110,808 patients underwent 131,629 inguinal hernia repairs during the study years; procedures were performed by 897 surgeons at 36 hospitals. Most repairs were open (65.4%), followed by laparoscopic (33.5%) and robotic (1.1%). Reoperation rates at 5 and 10 years of follow-up were 2.4% and 3.4%, respectively; rates were similar across surgical groups. In adjusted analysis, surgeons with higher laparoscopic volumes had a lower reoperation risk (27-46 average annual repairs: hazard ratio [HR] = 0.63, 95% confidence interval [CI] 0.53-0.74; ≥ 47 repairs: HR 0.53, 95% CI 0.44-0.64) compared to those in the lowest volume quartile (< 14 average annual repairs). No differences in reoperation rates were observed in reference to surgeon or hospital volume following open or robotic inguinal hernia repair. CONCLUSION: High-volume surgeons may reduce reoperation risk following laparoscopic inguinal hernia repair. We hope to better identify additional risk factors for inguinal hernia repair complications and improve patient outcomes with future studies.

The third International Congress on Myeloproliferative and Myelodysplastic Syndromes.

This meeting was convened by Richard T. Silver and co-chaired by Jerry L. Spivak. It was held from 27 to 29 October 2005 in Washington, DC. Thirty-one invited speakers from seven different countries participated in the conference, which was attended by more than 300 individuals from 23 countries. As in previous years, a clinical symposium for patients, held the day before the symposium, was sponsored by the Cancer Research and Treatment Fund, Inc., New York, NY 10021. This meeting report provides a summary of the five sessions prepared and highlighted by one of the session chairs. In addition to the formal presentations on the biology, clinical aspects and management of these diverse marrow stem cell disorders, there was considerable interest generated because of the availability of several new agents that have been recently approved. A special luncheon satellite symposium was devoted to the dramatic changes in the therapeutic options for the myelodysplastic syndromes, sponsored by MGI Pharma, Inc. The keynote address was presented by Dr. George Q. Daley from Harvard Medical School and the Children's Hospital Medical Center. He reviewed the molecular steps in the formation of the Philadelphia chromosome and some of the newly described mutations leading to resistance to chemotherapy (see Section 4).

The second international congress on myeloproliferative and myelodysplastic syndromes.

This meeting was convened by Richard T. Silver, M.D. and co-chaired by Jerry L. Spivak, M.D. It was held from 16 to 18 October 2003 in New York City, New York, USA. Thirty-nine invited speakers from nine different countries participated in the conference. There were more than 350 attendees. There were formal presentations and discussions on biology, clinical aspects, and management of patients with these diverse bone marrow stem cell disorders linked by a variable progression to acute myeloid leukemia. Of considerable interest, a clinical symposium exclusively for patients was held the day preceding the meeting at which John Bennett, Tiziano Barbui, Richard Silver, Jerry Spivak, and Ayalew Tefferi spoke on various topics pertaining to these diseases. This proved to be highly informative to the patients who reported that they enjoyed the program immensely. This was sponsored by the Cancer Research & Treatment Fund, Inc. Representatives of the Myelodysplasia Foundation were also present. This meeting report provides a summary of five different sections prepared by one or more of the session chairs. The keynote address was given by Shahin Rafii (Cornell Medical Center). Most appropriately, this talk focused on the expression and activation of angiogenic factors which play a crucial role in the progression of both myeloproliferative disorders and myelodysplastic syndromes (MDS). Among the known factors, vascular endothelial growth tyrosine kinase receptors (VEGF-R1, R2, and R3) support proliferation, survival, and mobility. Rafii's team has demonstrated that these receptors are expressed on subsets of primary hematopoietic cells as well as leukemic cells. Some leukemic cells express both VEGF-A and VEGF-R2, resulting in the generation of an autocrine loop that supports survival and within the osteoblastic zone translocating these cells to the vascular enriched niche for receipt of molecular instructions required for proliferation and differentiation. A pathologic correlation can be seen in some patients with the identification of abnormal localization of immature precursors (ALIP) in the central portions of the medullary cavity. Misplaced megakaryocytes can release pro-fibrotic factors, including platelet derived growth factors and transforming growth factor-beta. Collectively, these data suggest that chronic disregulation of angiogenic factors alter the microenvironment dislocating marrow stem cells that force both proliferation and differentiation in varying degrees, contributing to these hematological disorders.

Augmentation of anterior vertebral body screw fixation by an injectable, biodegradable calcium phosphate bone substitute.

STUDY DESIGN: A biomechanical study to evaluate the effects of a biodegradable calcium phosphate (Ca-P) bone substitute on the fixation strength and bending rigidity of vertebral body screws. OBJECTIVES: To determine if an injectable, biodegradable Ca-P bone substitute provides significant augmentation of anterior vertebral screw fixation in the osteoporotic spine. SUMMARY OF BACKGROUND DATA: Polymethylmethacrylate (PMMA) augmented screws have been used clinically; however, there is concern about thermal damage to the neural elements during polymerization of the PMMA as well as its negative effects on bone remodeling. Injectable, biodegradable Ca-P bone substitutes have shown enhanced fixation of pedicle screws. METHODS: Sixteen fresh cadaveric thoracolumbar vertebrae were randomly divided into two groups: control (no augmentation) (n = 8) and Ca-P bone substitute augmentation (n = 8) groups. Bone-screw fixation rigidity in bending was determined initially and after 10(5) cycles, followed by pullout testing of the screw to failure to determine pullout strength and stiffness. RESULTS: The bone-screw bending rigidity for the Ca-P bone substitute group was significantly greater than the control group, initially (58%) and after cyclic loading (125%). The pullout strength for Ca-P bone substitute group (1848 +/- 166 N) was significantly greater than the control group (665 +/- 92 N) (P < 0.01). Stiffness in pullout for the Ca-P bone substitute groups (399 +/- 69 N/mm) was significantly higher than the control group (210 +/- 51 N/mm) (P < 0.01). CONCLUSION: This study demonstrated that augmentation of anterior vertebral body screw fixation with a biodegradable Ca-P bone substitute is a potential alternative to the use of PMMA cement.

Use of hydroxyapatite in spine surgery.

Hydroxyapatite- (HA-)based ceramics have been evaluated for a variety of applications in spinal surgery, utilizing in vivo animal models and human clinical series. In vivo animal studies have shown efficacy for these materials as a bone graft substitute in interbody fusions and as a bone graft extender or bioactive osteoinductive material carrier in posterolateral lumbar fusions. Clinically, HA ceramic has been shown to be effective as a bone graft extender in posterior spinal fusion surgery for childhood scoliosis, and as a structural bone graft substitute in anterior cervical spine fusions. As an osteoconductive material, it appears to function best as a bone graft extender or carrier for an osteoinductive bone growth factor rather than as a stand-alone bone graft substitute in nonstructural clinical applications. Injectable HA ceramics also hold promise as biocompatible and bioresorbable materials for use in spinal screw fixation strength augmentation and in minimally invasive vertebral body strength augmentation either following fracture or prophylactically in osteoporotic vertebrae.

A mail survey of United States hematologists and oncologists: a comparison of business reply versus stamped return envelopes.

Mailed surveys are a popular means of obtaining data on large populations. In July 1999 a mail survey was conducted among 3000 randomly selected members of the American Society of Hematology to assess their approach to diagnosis and treatment of polycythemia vera. Because the researchers and the study population are members of the same professional organization with a vested interest in the results, we anticipated that the advantages of return stamped postage seen in previous studies would be less significant. The response rate for stamped return envelopes was 38% versus 32% for business reply envelopes. This statistically significant difference (P =.0005) of six percentage points is comparable to previous research. Excluding labor, the total cost per returned survey was $2.62 for business reply envelopes versus $1.82 for stamped return envelopes. We conclude that stamped return envelopes are a more effective and cost-efficient means of procuring data from physician specialists.

Erythropoietin use and abuse: When physiology and pharmacology collide.

The major function of the erythrocyte is to transport oxygen from the lungs to the other tissues, a function ensured by the glycoprotein hormone erythropoietin which couples red cell production to long term tissue oxygen requirements. Tissue hypoxia is the only physiological mechanism for increasing erythropoietin production but there are a variety of mechanisms for its down regulation including hyperoxia, increased catabolism by an expanded erythroid progenitor cell pool, blood hyperviscosity independently of its oxygen content, renal disease and the cytokines produced in inflammatory, infectious and neoplastic disorders. Erythropoietin lack results in severe and often transfusion-dependent anemia but if bone marrow function is otherwise normal, recombinant human erythropoietin therapy can restore the red cell mass and alleviate the transfusion need. However, elevation of the red cell mass by recombinant human erythropoietin is associated with a reduction in plasma volume and in some patients, hypertension is induced. Elevation of the red cell mass is also associated with a reduction in cerebral blood flow. When used to gradually elevate the hematocrit to 36% in anemic patients, recombinant human erythropoietin therapy is usually uneventful. However, when the normal hematocrit level is exceeded, the risk for thrombotic events increases since blood viscosity varies exponentially with the hematocrit. Increasing the hematocrit by autologous blood transfusions can enhance athletic performance in fit individuals and recombinant human erythropoietin administration is an obvious surrogate for autologous blood transfusions. However, paradoxically, its effects are the opposite of those of endurance training, namely a change in red cell mass without an increase in the total blood volume. Thus, the use of recombinant human erythropoietin as a performance-enhancing agent is dangerous, particularly in the less fit athlete, and probably of little benefit in the highly conditioned one. Differences in the carbohydrate content of native and recombinant human erythropoietin are identifiable by isoelectric focusing, providing a direct means for detecting erythropoietin abuse using urine specimens; a panel of surrogate blood markers of enhanced erythropoiesis such as soluble transferrin receptors, serum erythropoietin, reticulocyte hematocrit and percent macrocytes provide an indirect means for this purpose. Timing of surveillance is, of course, critical due to biological limitations on the physical presence of the hormone. However, education about its dangers may prove to be the most valuable solution to abuse of recombinant human erythropoietin for competitive advantage.

Instrumented posterior arthrodesis of the lumbar spine in patients with diabetes mellitus.

The existence of diabetes mellitus has been postulated to have a deleterious effect on the outcome following lumbar spine surgery. We retrospectively examined the records and radiographs of 32 diabetic patients (mean age, 60 years) who underwent posterior lumbar fusions using transpedicular instrumentation and iliac crest autograft. Ten patients were insulin-dependent and 22 required oral hypoglycemic agents for at least 1 year prior to surgery. The minimum follow-up time was 2 years after surgery (mean, 2.5 years). Surgical indications included herniated lumbar disk, lumbar spinal stenosis, thoracolumbar trauma, and lumbar pseudarthrosis. Clinical results were evaluated by chart review and/or interview by using Odom's criteria. At follow-up, 75% of patients were graded as excellent or good, and 25% as fair or poor. Twenty-five of 32 patients (78%) had improvement of back pain. Twenty of 27 (74%) patients had improvement of leg pain. Eight of 15 (53%) patients had improvement in motor strength, and 6 of 11 (54%) had improvement in light-touch sensation. Insulin dependence and the presence of polyneuropathy were associated with a poorer outcome. The average time to radiographic fusion was 5 months. Twenty-nine of 32 patients (91%) developed solid fusion by strict radiographic criteria. The three patients with a pseudarthrosis had persistent back pain and a poor result. Ten of 32 (31%) of the patients experienced perioperative complications, including prolonged wound drainage (n = 5), deep wound infection (n = 1), superficial wound infection (n = 1), atrial fibrillation (n = 1), ruptured cerebral aneurysm (n = 1), and ulnar nerve neuropathy (n = 1). We conclude that posterolateral lumbar spinal fusion with internal fixation in diabetic patients yields clinical results comparable to those of nondiabetic patients, with similar risks of perioperative complications.

The blood in systemic disorders.

* The high rate of proliferation required of the bone marrow renders it highly susceptible to the influence of external factors. * Anaemia is the most common haematological abnormality seen in systemic disorders. * In the anaemia of chronic disease, erythropoietin production is reduced and proliferation of erythroid progenitor cells is also impaired; this anaemia can generally be alleviated by correction of the underlying disease process. * The status of the endocrine system must always be considered in evaluation of a normocytic, normochromic anaemia. * Anaemia in infection can be due to host or parasite factors or to the treatment administered. * Anaemia due to malignant disease responds to erythropoietin therapy in many cases; failure to respond is a poor prognostic sign.

Internal fixation of cervical trauma following corpectomy and reconstruction. The effects of posterior element injury.

Although biomechanical data indicates that anterior fixation alone in unstable cervical injuries may not provide adequate stability, reports of clinical series indicate general success with this method of treatment. The specific contribution of posterior column injury to overall stability following reconstruction has not been evaluated. This study examined the biomechanical stability of anterior and/or posterior plate fixation following anterior corpectomy and reconstruction for unstable cervical injuries with varying degrees of posterior element injury. The C4-C6 motion segments of ten fresh frozen bovine cervical spines were used. After mounting, nondestructive mechanical testing in axial compression, torsion, flexion, extension, and lateral bending was done as an intact control. A C5 corpectomy with reconstruction using a synthetic bone graft was performed and the posterior ligaments sectioned at the C5-C6 level. Each specimen was sequentially instrumented with anterior and posterior plating alone and in combination and each construct was mechanically retested. The specimens were then further destabilized by bilateral facetectomies at C5-C6 and again tested with the same instrumentation combinations. In comparison to the controls, the spines with a C5 corpectomy/bone graft and posterior ligament rupture with anterior plating demonstrated significantly increased stiffness in flexion, extension, and lateral bending; posterior plating increased stiffness in only flexion and lateral bending. In axial compression and torsion, anterior or posterior plating demonstrated stiffness similar to the controls. Further destabilization by facetectomy significantly decreased stiffness of the instrumented construct (less than control) in torsion with anterior or posterior plate fixation alone. Combined plating showed increased stability compared to controls in all loading conditions for both patterns of instability. Anterior plating alone was able to restore the stability of the cervical spines with posterior ligamentous injury after corpectomy, but it failed to do so with the addition of bilateral facetectomies. For the unstable cervical spine with significant bilateral loss of posterior bony contact, anterior or posterior plating alone may not provide sufficient stabilization in the absence of any additional external immobilization. Combined plating should be considered, which may obviate the need for external immobilization.

Use of the anterior interbody fresh-frozen femoral head allograft in circumferential lumbar fusions.

Many studies in the literature have documented the outcome of circumferential lumbar fusions. However, no study has specifically evaluated the performance of the anterior fresh-frozen femoral head allograft as a structural interbody graft material. All office and hospital records, including charts and radiographs, were reviewed to obtain pertinent clinical and radiographic information. The cases included 23 single-level fusions, 22 two-level fusions, and 5 fusions of three or more levels. In all, 88 fusion levels were analyzed radiographically. The mean follow-up time was 28 months (range, 24 to 36 months). All procedures were performed in a single stage. At the latest follow-up, clinical outcome was graded good to excellent in 39 (78%) cases, fair in 8 (16%) cases, and poor in 3 (6%) cases. The average time to anterior radiographic fusion was 6 months (range, 4 to 8 months). The overall fusion rate was 98%. The average preoperative anterior disk space height was 10 mm, 14 mm immediately after operation, and 13 mm at follow-up. The posterior disk space height averaged 5 mm before operation, 7 mm immediately after operation, and 6 mm at follow-up. The average segmental lordosis was 7 degrees before operation, 10 degrees immediately after operation, and 10 degrees at follow-up. Late postoperative disk space collapse of 3 mm or more was noted in 17% of the fused disk spaces examined. Seventy-eight percent of the disk spaces maintained a disk space height greater than that of their preoperative value at the latest follow-up. Segmental lordosis did not change significantly at follow-up. The occurrence of collapse did not correlate with the clinical result, smoking history, or surgical indication (p < 0.05). Perioperative complications included one pleural effusion, two urinary tract infections, and one deep wound infection. Late complications included five painful graft sites and two patients with pseudarthrosis. Fresh-frozen femoral head allograft fulfills its desired function as an anterior structural graft in combination with rigid posterior transpedicular fixation, maintaining the disk space height achieved at surgery while reliably allowing remodeling and incorporation into a solid anterior fusion.

Current thinking and treatment practices in anaemia--an interactive poll.

At the recent EHA meeting in Birmingham, UK, an expert audience of haematologists and oncologists were polled using keypad technology on current thinking and treatment practices in anaemia in cancer patients. More than 76% of the audience thought that anaemia had a significant negative impact on the quality of life of cancer patients. The majority (> 60%) would institute treatment on the basis of appropriate symptoms rather than haemoglobin level, although among those who would use haemoglobin levels, there was no consensus on the concentration at which they would start treatment. The majority of respondents (54%) chose not to use the serum erythropoietin level as a guide as to when to institute therapy with recombinant human erythropoietin (rHuEPO) but, of those who would use it, 55% would use onlythe haemoglobin or haematocritto identify those responding within thefirst 2-4weeks of treatment. The remainder of the session used three case studies to investigate current treatment practices.

Posttranslational processing of the thrombopoietin receptor is impaired in polycythemia vera.

Recently, we demonstrated a marked reduction in the expression of the thrombopoietin receptor, Mpl, in polycythemia vera (PV) platelets and megakaryocytes using an antiserum against the Mpl extracellular domain. To further examine this abnormality, we raised an antibody to the Mpl C-terminus. Immunologic analysis of PV platelets with this antiserum confirmed the reduction in Mpl expression. However, the C-terminal antiserum detected 2 forms of Mpl in PV platelets in contrast to normal platelets, in which a single form of Mpl was detected by both the extracellular domain and C-terminal antisera. Two-dimensional gel electrophoresis studies with isoelectric focusing in the first dimension identified normal platelet Mpl as an 85 to 92 kD protein with an isoelectric point (pI) of 5.5. PV platelets contained an additional 80 to 82 kD Mpl Mpl isoform with a pI of 6.5. Analysis of Mpl expressed by the human megakaryocytic cell line, Dami, showed 2 isoforms similar to those found in PV platelets suggesting a precursor-product relationship. Digestion of Dami cell and normal platelet lysates with neuraminidase converted the more acidic Mpl isoform to the more basic one, indicating that the 2 isoforms differed with respect to posttranslational glycosylation. Furthermore, in contrast to normal platelet Mpl, PV platelet Mpl was susceptible to endoglycosidase H digestion, indicating defective Mpl processing by PV megakaryocytes. The glycosylation defect was specific for Mpl, as 2 other platelet membrane glycoproteins, glycoprotein IIb and multimerin, were processed normally. Importantly, the extent of the PV platelet Mpl glycosylation defect correlated with disease duration and extramedullary hematopoiesis.

The use of an injectable, biodegradable calcium phosphate bone substitute for the prophylactic augmentation of osteoporotic vertebrae and the management of vertebral compression fractures.

STUDY DESIGN: A biomechanical study comparing two materials for augmentation of osteoporotic vertebral bodies and vertebral bodies after compression fracture. OBJECTIVES: To compare an injected, biodegradable calcium phosphate bone substitute with injected polymethylmethacrylate bone cement for strengthening osteoporotic vertebral bodies and improving the integrity of vertebral compression fractures. SUMMARY OF BACKGROUND DATA: Injection of polymethylmethacrylate bone cement into fractured vertebral bodies has been used clinically. However, there is concern about thermal damage to the neural elements during polymerization of the polymethylmethacrylate bone cement as well as its negative effects on bone remodeling. Biodegradable calcium phosphate bone substitutes have been studied for enhancement of fixation in fractured vertebrae. METHODS: Forty fresh osteoporotic thoracolumbar vertebrae were used for two separate parts of this study: 1) injection into osteoporotic vertebrae: intact control (n = 8), calcium phosphate (n = 8), and polymethylmethacrylate bone cement (n = 8) groups. Each specimen then was loaded in anterior compression until failure; 2) injection into postfractured vertebrae: calcium phosphate (n = 8) and polymethylmethacrylate bone cement (n = 8) groups. Before and after injection, the specimens were radiographed in the lateral projection to determine changes in vertebral body height and then loaded to failure in anterior bending. RESULTS: For intact osteoporotic vertebrae, the average fracture strength was 527 +/- 43 N (stiffness, 84 +/- 11 N/mm), 1063 +/- 127 N (stiffness, 157 +/- 21 N/mm) for the group injected with calcium phosphate, and 1036 +/- 100 N (stiffness, 156 +/- 8 N/mm) for the group injected with polymethylmethacrylate bone cement. The fracture strength and stiffness in the calcium phosphate bone substitute group and those in the polymethylmethacrylate bone cement group were similar and significantly stronger than those in intact control group (P < 0.05). For the compression fracture study, anterior vertebral height was increased 58.5 +/- 4.6% in the group injected with calcium phosphate and 58.0 +/- 6.5% in the group injected with polymethylmethacrylate bone cement as compared with preinjection fracture heights. No significant difference between the two groups was found in anterior vertebral height, fracture strength, or stiffness. CONCLUSION: This study demonstrated that the injection of a biodegradable calcium phosphate bone substitute to strengthen osteoporotic vertebral bodies or improve vertebral compression fractures might provide an alternative to the use of polymethylmethacrylate bone cement.

The effect of locking fixation screws on the stability of anterior cervical plating.

STUDY DESIGN: Current anterior cervical plate systems were tested with locked and unlocked fixation screws and with unicortical and bicortical fixation screws to determine fixation rigidity and pull-off strengths. OBJECTIVES: To evaluate the effects of screw-plate locking and screw length on fixation strength and stability of anterior cervical plates. SUMMARY OF BACKGROUND DATA: New plate systems provide for rigid locking of the screw-plate interface, theoretically increasing construct rigidity, allowing unicortical fixation, and preventing screw back-out. There are few data on the effects of locking screws on the stability of anterior cervical plating. METHODS: Eighty fresh lamb vertebrae (C3-T1) were used. Test systems included: Cervical Spine Locking Plate (CSLP; Synthes, Paoli, PA, Orion plate (Sofamor-Danek, Memphis, TN), and Acroplate (AcroMed, Cleveland, OH). The CSLP and Orion plates were tested with fixation screws, locked and unlocked, and the AcroMed plate with unicortical and bicortical screw purchase. Biomechanical testing of the screw-plate constructs was performed to determine the initial bone-plate rigidity and pull-off strength. A 2.5-Nm cyclic bending moment was then applied to additional constructs for 10(5) cycles, and these constructs retested. RESULTS: Locked CSLP and Orion constructs were more rigid than all unlocked unicortical systems initially and after cyclic loading (P < 0.05). After cycling, the rigidity of all unlocked unicortical constructs decreased significantly (P < 0.05). There was no significant difference in pull-off strengths between the CSLP, the Orion, and the unicortical AcroMed plate. However, all had significantly less pull-off strength than the AcroMed plate with bicortical screws. A negative correlation was observed between initial pull-off strength and sagittal vertebral body diameter. CONCLUSIONS: Locking screws significantly increased the rigidity of the tested screw-plate systems initially and after cyclic loading. Because pull-off strength was affected by the vertebral body diameter, use of longer unicortical screws may be clinically beneficial in the patient with larger cervical vertebrae.

Immunoablative high-dose cyclophosphamide without stem-cell rescue for refractory, severe autoimmune disease.

BACKGROUND: Immunoablative high-dose cyclophosphamide without stem-cell rescue induces durable, complete remission in most patients with aplastic anemia. OBJECTIVE: To determine the efficacy of high-dose cyclophosphamide in various refractory, severe autoimmune diseases. DESIGN: Prospective phase II study. SETTING: Johns Hopkins University (Baltimore, Maryland) and Hahnemann University (Philadelphia, Pennsylvania). PATIENTS: Eight patients with refractory, severe autoimmune disease. INTERVENTION: Immunoablative high-dose cyclophosphamide (50 mg/kg of body weight per day) for 4 consecutive days. MEASUREMENTS: Clinical and laboratory variables of autoimmune disease. RESULTS: Seven patients improved markedly: Five achieved complete remission and two achieved partial remission. Four patients have remained in continuous complete remission for 3 to 21 months, and two patients in partial remission continue to improve after 14 and 19 months of follow-up. High-dose cyclophosphamide was well tolerated; median times to a neutrophil count of 0.5 x 10(9) cells/L and platelet transfusion independence were 17 and 16 days, respectively. CONCLUSIONS: Immunoablative high-dose cyclophosphamide without stem-cell rescue can induce complete remission in patients with refractory, severe autoimmune disease. Reemergence of marrow function is similar to that seen after autologous transplantation and does not carry the risk for reinfusion of autoaggressive lymphocytes with the autograft.