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Joseph M Jaworski,1,2 Vanlila K Swami,1 Rebecca C Heintzelman,1 Carrie A Cusack,3 Christina L Chung,3 Jeremy Peck,3 Matthew Fanelli,3 Micheal Styler,4 Sanaa Rizk,4 J Steve Hou1 1Department of Pathology and Laboratory Medicine, Hahnemann University Hospital/Drexel University College of Medicine, Philadelphia, PA, USA; 2Department of Pathology, Mercy Fitzgerald Hospital, Darby, PA, USA; 3Department of Dermatology, Hahnemann University Hospital/Drexel University College of Medicine, Philadelphia, PA, USA; 4Department of Hematology/Oncology, Hahnemann University Hospital/Drexel University College of Medicine, Philadelphia, PA, USA Abstract: Blastic plasmacytoid dendritic cell neoplasm is an uncommon malignancy derived from precursors of plasmacytoid dendritic cells. Nearly all patients present initially with cutaneous manifestations, with many having extracutaneous disease additionally. While response to chemotherapy initially is effective, relapse occurs in most, with a leukemic phase ultimately developing. The prognosis is dismal. While most of the clinical and pathologic features are well described, the association and possible prognostic significance between peripheral blood absolute monocytosis (>1.0 K/µL) and blastic plasmacytoid dendritic cell neoplasm have not been reported. We report a case of a 68-year-old man who presented with a rash for 4–5 months. On physical examination, there were multiple, dull-pink, indurated plaques on the trunk and extremities. Complete blood count revealed thrombocytopenia, absolute monocytosis of 1.7 K/µL, and a negative flow cytometry study. Biopsy of an abdominal lesion revealed typical features of blastic plasmacytoid dendritic cell neoplasm. Patients having both hematologic and nonhematologic malignancies have an increased incidence of absolute monocytosis. Recent studies examining Hodgkin and non-Hodgkin lymphoma patients have suggested that this is a negative prognostic factor. The association between blastic plasmacytoid dendritic cell neoplasm and absolute monocytosis has not been described and may, in fact, have prognostic value. Keywords: blastic, plasmacytoid, dendritic, monocytosis

Rhabdomyosarcoma (RMS) is the most common soft-tissue tumor in childhood, but is extremely rare in elderly. We present a rare case of cardiac RMS, which developed 1 year after the diagnosis and management of acute lymphoblastic leukemia in a 68-year-old female. The occurrence of such phenomena is intriguing, especially in an individual without prior history of malignancy at a younger age. Through the review of the existing literature, we attempt to approach the pathogenesis and clinical manifestations of this rare clinical entity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Chronic myeloid leukemia (CML) is defined by the presence of Philadelphia chromosome resulting from a reciprocal translocation between chromosomes 9 and 22 [t9;22] that gives rise to a BCR::ABL1 fusion gene. CML occurs in 3 different phases (chronic, accelerated, and blast phase) and is usually diagnosed in the chronic phase in developed countries. Tyrosine kinase inhibitor (TKI) therapy is a highly effective treatment option for patients with chronic phase-CML. The primary goal of TKI therapy in patients with chronic phase-CML is to prevent disease progression to accelerated phase-CML or blast phase-CML. Discontinuation of TKI therapy with careful monitoring is feasible in selected patients. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with chronic phase-CML.

Objective: We aimed to analyze the Health Care Utilization Project's (HCUP) Nationwide Inpatient Sample (NIS) and compare mortality rates in hospitals by month to determine if there is seasonal variability in outcomes associated with venous thromboembolism (VTE)., Methods: The Nationwide Inpatient Sample database was queried from 1998 to 2011. Inclusion criteria were a diagnosis of deep vein thrombosis (DVT) (ICD-9 {International Classification of Diseases, Ninth Revision, Clinical Modification} 453.4, 453.8) and/or VTE (ICD-9 415.1) in patients aged 18 years or more. Admission data was then analyzed to compare mortality rates in teaching and non-teaching hospitals over that time and by month. Demographics, Charlson Comorbidity Index, length of stay (LOS), hospital region, and admission types (emergent/urgent versus elective admissions) were assessed. Linear and logistic models were generated for complex survey design to analyze predictors of mortality and LOS., Results: A total of 1,449,113 DVT/VTE cases were identified in the Nationwide Inpatient Sample (weighted n= 7,150,613), 54.7% female, 56.38% white, 49% in teaching hospitals. Higher mortality was found in the months of November 6.52%, December 6.9%, January 6.94%, and February 6.93% versus overall mortality of 6.4% over 12 months. Higher mortality was noted in these winter months in all regions, along with a significantly increased LOS. Mortality in the total cohort was found to be higher in January, with odds ratio (OR) 1.11 (1.08-1.15), p<0.0001; February, OR 1.11 (1.07-1.15), p<0.0001; and December, OR 1.10 (1.06-1.14), p<0.0001 compared to June. Mortality was significantly lower in the Midwest or North Central regions (OR 0.78 {0.72-0.83}, p<0.0001) and West (OR 0.80 {0.73-0.87}, p<0.0001) compared to the Northeast. Mortality was also significantly higher in teaching hospitals than in non-teaching hospitals (OR 1.16 {1.10-1.22}, p<0.0001), with mortality trending higher in teaching hospitals each month. Emergent/urgent admission, larger hospital size, female sex, age, and urban location were also significantly associated with increased mortality., Conclusions: This national study identified an increased risk of mortality associated with hospitalizations for DVT/VTE in the winter months, independent of hospital teaching status or region., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Styler et al.)

Background/aim: Anticancer peptide PNC-27 binds to HDM-2 protein on cancer cell membranes inducing the formation of cytotoxic transmembrane pores. Herein, we investigated HDM-2 membrane expression and the effect of PNC-27 treatment on human non-stem cell acute myelogenous leukemia cell lines: U937, acute monocytic leukemia; OCI-AML3, acute myelomonocytic leukemia and HL60, acute promyelocytic leukemia., Materials and Methods: We measured cell surface membrane expression of HDM-2 using flow cytometry. Cell viability was assessed using MTT assay while direct cytotoxicity was measured by lactate dehydrogenase (LDH) release and induction of apoptotic markers annexin V and caspase-3., Results: HDM-2 is expressed at high levels in membranes of U937, OCI-AML3 and HL-60 cells. PNC-27 can bind to membrane HDM-2 to induce cell necrosis and LDH release within 4 h., Conclusion: Targeting membrane HDM-2 can be a potential strategy to treat leukemia. PNC-27 targeting membrane HDM-2 demonstrated significant anti-leukemia activity in a variety of leukemic cell lines., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Gastrointestinal stromal tumor (GIST) is the most common primary mesenchymal neoplasm of the gastrointestinal tract. Mutations of KIT and platelet-derived growth factor receptor alpha have been well characterized in GISTs. Patients with KIT mutations are generally sensitive to treatment with tyrosine kinase inhibitors. However, some patients with GIST, while initially sensitive to TKIs, gain resistance in later stages of treatment. Heterologous rhabdomyomsarcomatous dedifferentiation of advanced GISTs after long-term imatinib mesylate (IM) therapy has been reported. In these cases, the underlying molecular mechanism of tumor progression and transformation is unclear., Case Presentation: We report one such patient with rhabdomyosarcomatous dedifferentiation of a GIST without metastatic disease after brief 3-month therapy with IM. The tumor was composed of two distinct phenotypes, a CD117 negative region with rhabdomyosarcomatous differentiation directly adjacent to a CD117 positive classic GIST region. Molecular analysis identified the activating KIT exon 11 mutation in both regions, indicating a common origin for both phenotypes. Additionally, the dedifferentiated component contained two synonymous variants in platelet-derived growth factor receptor alpha and KIT. The increased number of synonymous variants in the rhabdomyosarcomatous region may reflect increased genetic instability of this tumor that may have resulted in the loss of CD117 expression in the dedifferentiated component., Conclusion: This study adds to the growing consensus that rhabdomyosarcomatous GIST progresses from a common GIST primary tumor. The role of IM in this progression is uncertain; however short duration of IM treatment in this study supports the hypothesis that rhabdomyosarcomatous GIST progression is not a consequence of IM therapy. Furthermore, we provide additional information supporting the observation that CD117 negative rhabdomyosarcomatous transformation maintains the activating KIT variant without KIT expression.

An exceedingly rare manifestation of leukemia, termed neuroleukemiosis, involves peripheral nerve infiltration by leukemic cells. Patients with neuroleukemiosis typically present with a peripheral neuropathy and/or chloromatous masses. The diagnosis is supported by, and established with, electrophysiologic testing, imaging, histopathology, and immunophenotyping. We present the case of 21 year old male with multiply relapsed M4 type of acute myelogenous leukemia (AML) who presented with extremity pain and was subsequently found to have multiple cervical, thoracic, and lumbosacral nerve root masses. A diagnosis of neuroleukemiosis was established via CT-guided biopsy and immunophenotyping. The patient's neuroleukemiosis responded well to chemotherapy, donor lymphocyte infusions, and spinal irradiation. The literature is reviewed regarding this interesting and rare clinical condition., (Copyright © 2019. Published by Elsevier B.V.)

Background: Bloodless pancreatic surgery (BPS) is rarely performed and/or reported. We aim to characterize perioperative and anesthetic strategies in BPS., Materials and Methods: A literature search was performed on MEDLINE looking for case reports/case series using search terms ("Jehovah's Witness" [All Fields]) AND ("Pancreatic Surgery" [All Fields] OR "Pancreaticoduodenectomy" [All Fields] OR "Distal Pancreatectomy" [All Fields]). Data regarding categorical variables are reported as proportions and quantitative continuous variables as medians with ranges or means with standard deviation. Forty-one patients requiring BPS are reported in the literature with three additional cases from our institution (n = 44). The data analyzed included clinicopathologic factors, BPS strategies, patient complications, and in-hospital mortality., Results: The most common procedure and diagnosis were pancreaticoduodenectomy (n = 34, 77.3%) and pancreatic ductal adenocarcinoma (n = 12, 27.3%), respectively. Transfusion reduction strategies in BPS fell into three categories: preoperative, intraoperative, and postoperative. Preoperative strategies included iron supplementation (n = 24, 54.5%) and erythropoietin administration (n = 14, 41.2%). Intraoperative strategies included acute normovolemic hemodilution (n = 30, 68%) and cell saver (n = 4, 9.1%). Postoperative strategies included erythropoietin (n = 16, 48.5%) and iron supplementation (n = 16, 48.5%). Complications occurred in 21 (60%) patients. There was no in-hospital mortality among the 44 patients in this cohort., Conclusions: A broad spectrum of bloodless medicine and surgery practices were used based on patient selection, multidisciplinary practice, and preference. With careful perioperative and anesthetic management, BPS can be performed with good outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The initial diagnosis of heparin-induced thrombocytopenia (HIT) is made on clinical grounds because the assays with the highest sensitivity (eg, heparin-platelet factor 4 antibody enzyme-linked immunosorbent assay [ELISA]) and specificity (eg, serotonin release assay) may not be readily available. The clinical utility of the pretest scoring system, the 4Ts, was developed and validated by Lo et al in the Journal of Thrombosis and Haemostasis in 2006. The pretest scoring system looks at the degree and timing of thrombocytopenia, thrombosis, and the possibility of other etiologies. Based on the 4T score, patients can be categorized as having a high, intermediate, or low probability of having HIT. We conducted a retrospective study of 100 consecutive patients who were tested for HIT during their hospitalization at Hahnemann University Hospital (Philadelphia, PA) in 2009. Of the 100 patients analyzed, 72, 23, and 5 patients had 4T pretest probability scores of low, intermediate, and high, respectively. A positive HIT ELISA (optical density > 1.0 unit) was detected in 0 of 72 patients (0%) in the low probability group, in 5 of 23 patients (22%) in the intermediate probability group, and in 2 of 5 patients (40%) in the high probability group. The average turnaround time for the HIT ELISA was 4 to 5 days. Fourteen (19%) of the 72 patients with a low pretest probability of HIT were treated with a direct thrombin inhibitor. Ten (71%) of the 14 patients in the low probability group treated with a direct thrombin inhibitor had a major complication of bleeding requiring blood transfusion support. In this retrospective study, a low 4T score showed 100% correlation with a negative HIT antibody assay. We recommend incorporating the 4T scoring system into institutional core measures when assessing a patient with suspected HIT, selecting only patients with intermediate to high probability for therapeutic intervention, which may translate into reduced morbidity and lower health care costs.

Intracerebral relapse of Hodgkin lymphoma is a rare occurrence, with a reported incidence of < 0.5%. To the best of our knowledge, only 4 cases have been reported in the literature. We report the case of a human immunodeficiency virus (HIV)-seropositive man with disseminated Hodgkin lymphoma who presented with left facial weakness and sensory abnormalities as the only symptoms of disease progression 3 months after chemotherapy-induced disease remission. Because of the relative rarity of the condition, there are no randomized controlled trials or evidence-based strategies for managing patients with HIV and intracerebral Hodgkin lymphoma. The diagnostic difficulty of this case emphasizes the necessity for a high index of suspicion for the diagnosis of HIV-associated intracerebral lymphoma in the appropriate clinical setting. In the post-genomic era, the development of sophisticated clinical and/or molecular biomarkers could contribute to earlier diagnosis and potentially improve disease prognosis.

Appendiceal carcinoma is a very rare clinical entity, constituting 1% of all colorectal malignancies and 1% of all appendectomy specimens. Appendiceal malignancies often present atypically, thus creating diagnostic challenges. We present a patient with mucinous carcinoma of the appendix who presented with hematuria and abdominal pain. Similar case reports are extremely rare in the literature, while typical presentations of appendiceal carcinoma include abdominal pain, abdominal mass, early satiety, nausea, and iron-deficiency anemia. Initially, the diagnostic investigation in our patient was focused on urinary tract disorders, but ultimately resulted in finding a mucinous appendiceal carcinoma. The carcinoma had invaded the urinary bladder and was disseminated in the peritoneal cavity. Aggressive cytoreductive surgery is the most common therapeutic approach for disseminated tumors, often followed by intraperitoneal chemotherapy. However, treatment should be individualized based on patient-specific parameters, such as the presence of comorbidities, performance status, as well as the presence of metastatic disease. Our patient had optimal cytoreduction with subsequent systemic therapy with 5-fluorouracil, leucovorin, oxaliplatin, and bevacizumab, a monoclonal antibody directed against vascular endothelial growth factor. She completed her treatment regimen without complications and is currently being restaged. An integrative approach is required in the diagnostic investigation and management of appendiceal malignancies.

Platelet glycoprotein IIb/IIIa receptor inhibitors have been shown to improve outcomes in percutaneous coronary interventions. Their use with multiple anticoagulants has been associated with increased bleeding complications. Among these, alveolar hemorrhage is a rare and potentially fatal complication. Six patients with this complication were identified over a four-year period. Patient characteristics, possible risk factors, pathophysiology, prevention and potential treatment options are discussed.

Four patients with chronic inflammatory demyelinating polyneuropathy (CIDP) who were refractory to conventional treatment were treated with high-dose cyclophosphamide (200 mg/kg over 4 days). All improved in functional status and muscle strength. Nerve conduction studies improved in three of four. Other immunomodulatory medications have been discontinued. High-dose cyclophosphamide can be given safely to patients with CIDP and patients with disease persistence after standard therapy may have a response that lasts for over 3 years and results in long-term disease remission.

Cytotoxic therapy is a cornerstone for patients with severe systemic lupus erythematosus (SLE). High-dose cyclophosphamide, 200 mg/kg, can induce a complete remission without the need for stem cell rescue in patients with autoimmune illnesses. Here we report on our first four patients treated for severe SLE with this treatment approach. Patients received cyclophosphamide, 200 mg/kg, divided over 4 days. Starting day 10, patients received filgrastim, 5 micrograms/kg/day, until their absolute neutrophil count (ANC) rose to 10.0 x 10(9)/l for two consecutive days. Disease activity as evaluated by scores from the Systemic Lupus Activity Measure-2, the SLE Disease Activity Index and the Responder Index for Lupus Erythematosus were completed before and after high-dose therapy. Before high-dose cyclophosphamide, SLE disease duration ranged from 8 to 21 (mean 12.5) years. Their average disease activity measured by SLAM-2 and SLEDAI was 15.5 (range 11-19) and 23.25 (range 20-26), respectively. At a median of 22 (range 12-39) months of follow-up, mean disease activity measured by SLAM-2 and SLEDAI decreased to 6.25 and 7.75, respectively. All patients experienced febrile neutropenia. No long-term morbidities or mortalities were observed. High dose cyclophosphamide is a therapy capable of decreasing disease severity in poor prognosis SLE patients. Future study is warranted for both refractory patients as well as primary therapy for patients with moderate to severe disease presentations.

Administration of granulocyte colony-stimulating factor to patients undergoing high-dose chemotherapy and autologous peripheral blood stem cell transplantation accelerates neutrophil recovery and decreases hospitalization time. The optimal timing for granulocyte colony-stimulating factor infusion remains unknown. In this retrospective, case-controlled, two-armed study, we reviewed our experience at Hahnemann University Hospital to determine whether initiating granulocyte colony-stimulating factor infusions on posttransplant day 0 versus day 8 affects neutrophil recovery time, posttransplant discharge date, total hospital days after high-dose chemotherapy, and autologous peripheral blood stem cell transplantation. All patients hospitalized between 1994 and 1998 at Hahnemann University Hospital, Bone Marrow Transplantation Unit with breast cancer or non-Hodgkin's lymphoma, who underwent high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation and received granulocyte colony-stimulating factor either on posttransplant day 0 (16 patients) or day 8 (16 patients). The day 0 and day 8 groups had no statistically significant differences in age, sex, weight, height, body surface area, disease characteristics, pretransplant harvesting or conditioning regimens, or transplant CD34+ cell counts. Our main outcome measure was the mean time to reach absolute neutrophil count greater than or equal to 0.5 x 10(9)/l, the number of hospital days after transplant, and the total hospital days. The mean days to neutrophil recovery (10.56 versus 9.68, p = 0.48), posttransplant hospital days (13.62 versus 12.81, p = 0.39), and total hospital days (20.25 versus 20.25, p = 1.00) were not significantly different between day 8 and day 0 groups, respectively. No significant effects on neutrophil recovery time, posttransplant hospital days, or total hospital days were observed with the initial granulocyte colony-stimulating factor infusion on day 0 versus day 8 after transplant. Delayed administration may allow substantial cost savings (US$200 x 8 approximately equal to US $1,600 per patient) without affecting clinical outcome. More studies are needed to determine whether greater delay is feasible.

We report the previously undescribed occurrence of extramedullary blast crisis in a patient with chronic myelogenous leukemia in complete cytogenetic and molecular remission on interferon-alpha. Development of bilateral testicular swelling prompted a biopsy showing stromal infiltration with CD20 and TdT positive immature cells. On repeated examinations, the bone marrow remained BCR/ABL negative by RT-PCR analysis. However, the cerebrospinal fluid (CSF) contained atypical lymphocytes positive for the P210 BCR-ABL product. Following treatment with testicular irradiation, intrathecal methotrexate, systemic chemotherapy and an unrelated donor transplant, the patient showed no evidence of disease until 9 months post-transplant, when he relapsed in lymphoid blast crisis in both bone marrow and CSF.

Two cases with congenital homozygous factor XI deficiency developed a factor XI inhibitor following repeated plasma transfusions. Case 1 was given cyclophosphamide, intravenous immunoglobulin, and steroids. The factor XI inhibitor disappeared on day 103 and cardiac catheterization was performed without complications after giving fresh frozen plasma. Case 2 was effectively managed by plasma exchange for cardiac catheterization and surgery. However, after five plasma exchange procedures, the same plasma volume exchange was not effective in shortening the activated partial thromboplastin time (APTT). A significant heparin rebound occurred 4 h after heparin neutralization with protamine sulphate for which the patient needed to have a blood clot evacuated from around the heart.

Background: Chronic leukemia is a disease characterized by the malignant proliferation of immunologically incompetent lymphocytes. The knowledge of open heart surgery in patients with this disorder is limited., Methods: Twelve patients with chronic lymphocytic leukemia underwent open heart surgery (nine coronary artery bypass grafting (CABG), two aortic valve replacement (AVR), one CABG and AVR) from September 1991 to September 1996. There were nine males and three females with a mean age of 68 years (41-81 years). Staging was assigned according to the Rai Classification. There were seven Stage 0, two Stage I, zero Stage II, one Stage III and two Stage IV patients. Cardiopulmonary bypass (CPB) was performed using standard techniques of cannulation, moderate hypothermia and antegrade/retrograde cardioplegia., Results: Hospital mortality occurred in two (17%) patients. Both patients died of sepsis. Hospital morbidity occurred in seven (58%) patients. The most common complications were infections. Five patients were found to have other malignancies (basal cell, laryngeal, prostate, bladder and breast cancers). Transfusion of blood products was required in eight (67%) patients. The average length of stay was 15 days (7-50 days). Follow-up was complete. Late mortality occurred in four patients at a mean of 7 months (1-18 months). All deaths were non-cardiac related (ruptured AAA, kidney failure, respiratory failure and sepsis). Six patients remain alive at a mean of 25 months (1-48 months)., Conclusion: Hospital mortality and morbidity in patients with chronic lymphocytic leukemia undergoing open heart surgery are high. Infection is the leading cause of hospital death, as well as the most common complication. The majority of patients receive blood products during the course of their hospitalization. Late mortality is high and non-cardiac related. Based on these findings, a re-definition of the aims, goals and expectations of open heart surgery in patients with chronic leukemia is necessary. Suggestions in management are presented.

Arterial thrombosis as a presentation of acute promyelocytic leukemia is uncommon. The authors report a patient who presented with a clot in the left external iliac artery and pulmonary emboli. The literature is reviewed.

Splenomegaly is a common occurrence in the course of non-Hodgkin's lymphoma (NHL), sometimes leading to development of bulk symptoms or cytopenias. Splenomegaly may also be the primary manifestation of NHL. We reviewed our experience with diagnostic and therapeutic splenectomy for NHL over the past 3 years. In July of 1991, a prospective database had been established to evaluate elective splenectomy for hematologic disease; of 58 patients, 12 had NHL. Splenectomy was performed for diagnostic purposes, correction of cytopenias, and relief of bulk symptoms. Most patients had more than one indication for splenectomy. Operative hemorrhage requiring transfusion was seen only in patients with massive splenomegaly (> 1,500 g). Median postoperative hospital stay was 4 days. There was no operative mortality or major morbidity. Minor morbidity was seen in 17% of patients. A favorable hematologic response was seen in 80% of cytopenias at the 3-month postoperative interval. Splenectomy is safe and effective in appropriately selected patients with NHL.

Veno-occlusive disease continues to be a significant cause of morbidity and early mortality following bone marrow transplantation. This study retrospectively analyzes the incidence and risk factors for severe VOD in 350 patients treated with 4 days of busulfan (total 16 mg/kg) and 2 days of cyclophosphamide (120 mg/kg) at four marrow transplant centers. Using the criteria defined by McDonald et al (Hepatology 1984; 4: 116-122), 93/350 (27%) developed VOD (11% mild, 5% moderate and 11% severe). Multivariate analysis revealed the following risk factors to be significantly associated with severe VOD: pretransplant transaminase and alkaline phosphatase elevation, ciprofloxacin antibiotic prophylaxis, use of estrogen/progestins or vancomycin during the peritransplant period and methotrexate for GVHD prophylaxis. Mild to moderate grades of VOD were not associated with significantly increased mortality but mortality was higher in patients with severe VOD (31%, P = 0.0013). These data suggest that risk factors for VOD may depend on the preparative regimen used and suggest that use of these risk factors may identify a subgroup of patients that can be targetted for studies of prevention of VOD.

Twenty-five patients with hematologic malignancies were treated with busulfan (16 mg/kg) and cyclophosphamide (50 mg/kg x 3 days) as conditioning for bone marrow transplantation using marrow from serologically matched, DR locus genotypically identical unrelated donors. Previous studies of BuCy2 as conditioning for UD-BMT have reported a graft failure rate of up to 21% suggesting it may be insufficiently immunosuppressive in this setting. We elected not to use BuCy4 as it may have a higher incidence of extramedullary toxicity. In addition the patients received GM-CSF (500 mg/m2) from day 0, cyclosporine and short-course methotrexate (15 mg/m2 x 1, then 10 mg/m2 x 3) as GVHD prophylaxis and prophylactic ganciclovir at engraftment if either they or their donor were CMV antibody positive. The median age of the 25 patients was 41 years and the most common diagnosis was CML (76%). Seven patients were considered poor risk and eight males were recipients of marrow from female donors. Sixteen patients survive at a median of 435 days from transplant. The actuarial overall and disease-free survivals at 1 year in this group of older patients were 62 +/- 20% and 57 +/- 20% and 100-day survival was 70%. The engraftment rate was 100%; there have been no instances of secondary graft failure. Fifteen patients (60%) developed grade II-IV GVHD and 12 of 16 (75%) developed some chronic GVHD but only half of these were extensive. The performance status of survivors is good (median of 90); seven of 12 eligible patients are back at work. This study demonstrates that UD-BMT can be successfully performed in very closely HLA-matched older patients using a chemotherapy-only protocol and that low rates of severe acute GVHD can be achieved without T cell depletion.

Relapse is still a common problem after bone marrow transplant (BMT) and teh value of adding etoposide to standard conditioning agents is being tested. The aim of the study was to assess the extramedullary toxicity which resulted from adding etoposide to busulphan 16 mg/kg and cyclophoshamide 120 mg/kg (BuCY2). Eighty four patients received etoposide 40 mg/kg in addition to BuCY2 as conditioning for autologous and allogeneic BMT for leukemia and lymphoma. The Bearman system of grading extramedullary toxicity was used along with a system of grading skin toxicity that we devised. There were seven acute toxic deaths (8%) and in total 15 patients experienced life-threatening or fatal toxicity. The major finding was a striking increase in pulmonary toxicity with six deaths (five alveolar hemorrhage and one pulmonary embolus). Five of seven of the patients with severe pulmonary toxicity had been given irradiation to the lung fields (P < 0.001). Thirty nine per cent of patients had veno-occlusive disease of the liver but the case fatality rate was low (1 of 33). Dermatologic toxicity was experienced by 82% of patients and was symptomatically troublesome but rapidly reversible. The addition of etoposide to BuCY2 increases non-hematological toxicity. This regimen is associated with severe pulmonary toxicity in patients with a history of prior chest irradiation. A high incidence of skin toxicity was seen; a system for describing this toxicity is proposed.

We performed a retrospective analysis of 42 consecutive patients undergoing autologous BMT to determine the incidence of second and third degree heart block following the infusion of cryopreserved autologous bone marrow and to identify any predisposing characteristics. A decrease in heart rate > or = 10 beats/min was observed in 80.5% of patients, with a mean decrement of 27 +/- 7 beats/min. 48.8% of patients developed absolute bradycardia (< or = 60 beats/min). Four of 41 patients (9.7%) experienced high-grade heart block: 9.7% second degree and 4.8% third degree. Heart block patients did not differ from the non-heart block group with respect to age, interval from diagnosis or bone marrow harvest to transplant, cardiac risk factors, pretransplant electrocardiograms or radionuclide angiograms, transplant chemotherapy regimens or serum chemistry values. There was an increased incidence of heart block in patients with prior exposure to cyclophosphamide (p < 0.05) and vinca alkaloids (p < 0.05). There appears to be a high incidence of transient second and third degree heart block following autologous marrow infusion. This may be related to prior chemotherapy, but more likely is an effect of the infusate itself. Predisposing factors were not identified.

We used a subcutaneously administered GnRHa for 21 to 26 days prior to menotropin stimulation, to suppress endogenous LH surges in four patients participating in IVF. GnRHa-pretreated cycles were compared with previous menotropin treatment cycles. Endogenous LH surges were successfully suppressed in all patients. Peak E2 levels and ultrasonographic parameters of follicular development were comparable in the two treatment groups. Exogenous gonadotropin requirements were increased 2- to 4-fold in GnRHa pretreated cycles (P less than 0.05). Ovum recovery rates were not improved by adjuvant LA. These studies indicate that there was an increased ovarian requirement for exogenous gonadotropins as a result of GnRHa therapy. It has to be considered that this may be a direct effect of GnRHa upon the ovary. Alternatively, the absence of endogenous pituitary support in GnRHa-treated patients may account for the increased gonadotropin requirement. Finally, it is possible that this effect is indigenous to this select patient population of poor responders to menotropin stimulation, or to a specific effect of subcutaneously (as opposed to intranasally) administered GnRHa on the ovary. Further studies are needed to clarify the extent to which any or all of these postulated mechanisms may be influencing ovarian response to exogenous gonadotropins after subcutaneous GnRHa pretreatment.