Clinical and prognostic importance of XIAP and USP8 in advanced stages of non-small cell lung cancer.

PURPOSE: To investigate the relationship of the apoptosis regulators X-linked inhibitor of apoptosis (XIAP) and ubiquitin specific protease 8 (USP8) with clinical parameters, survival and response to chemotherapy in patients with advanced stages of non-small cell lung cancer (NSCLC). METHODS: The study included 34 NSCLC patients (28 females, 6 males) and 44 healthy individuals (17 males, 27 females) as a control group. XIAP and USP8 levels were determined by ELISA. RESULTS: The median serum XIAP level of the patients and the control group showed no significant difference. USP8 level was higher in patients than in controls (p<0.0001). In univariate analysis, there was no significant relationship between XIAP and USP8 serum levels and age, sex, performance status, weight loss, stage of disease, histopatological type and response to chemotherapy. Response to chemotherapy did not differ between the high and low XIAP and USP8 groups . There was no significant difference in progression- free survival (PFS) (p=0.432 and p=0.50, respectively) and overall survival (OS) (p=0.989 and p=0.90, respectively) between the low and high XIAP and USP8 groups. CONCLUSION: No relationship was found in serum XIAP and USP8 levels with clinical parameters, response to chemotherapy, PFS and OS in patients with advanced stages of NSCLC.

Gemcitabine and cisplatin combination chemotherapy in triple negative metastatic breast cancer previously treated with a taxane/anthracycline chemotherapy; multicenter experience.

This study was aimed to establish clinical efficacy and tolerability of gemcitabine and cisplatin combination in patients with metastatic triple negative breast cancer progressing after anthracycline and taxane based chemotherapies.Thirty-three patients who were given cisplatin and gemcitabine for triple negative and metastatic breast cancer were evaluated retrospectively. A total of 141 cycles were administered with a median 4 cycles per patient. Median follow-up time was 14 months (range, 2-36 months). Objective response rate was 27.3%. Total clinical benefit of the combination was 48.4%. The estimated median progression free survival and median overall survival were 5 months and 14 months, respectively. The most common Grade 3 and 4 toxicity were neutropenia and thrombocytopenia observed in 10 (27.7%) and 9 (24.9%) patients, respectively. The combination of the gemcitabine and cisplatin after taxane/anthracycline is well tolerated and seems to be effective with acceptable toxicity profile.

Gemcitabine alone versus combination of gemcitabine and cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a retrospective analysis of multicenter study.

The majority of patients with pancreatic cancer is of advanced disease. Several randomized Phase II and III trials suggest that the combination of gemcitabine and cisplatin (GemCis) response rates were higher than Gemcitabine (Gem) alone, however the trials were not enough powered to indicate a statistically significant prolongation of survival in patients with advanced pancreatic adenocarcinoma. The aim of this retrospective multicenter study is to evaluated the efficiency of Gem alone versus GemCis in patients with locally advanced and/or metastatic pancreatic adenocarcinoma .A total of 406 patients, from fourteen centers were evaluated retrospectively. All patients received Gem or GemCis as first-line treatment between September 2005 to March 2011. Primary end of this study were to evaluate the toxicity, clinical response rate, progression-free survival (PFS) and overall survival (OS) between the arms. There were 156 patients (M: 98, F: 58) in Gem arm and 250 patients (M: 175, F: 75) in the combination arm. Gemcitabin arm patients older than the combination arm ( median 63 vs 57.5, p=0.001). In patients with the combination arm had a higher dose reduction (25.2% vs 11.3%, p=0.001) and dose delay (34% vs 16.8%, p=0.001). Among patients with the combination and Gemcitabin arm gender, diabetes mellitus, performance status, cholestasis, grade, stage did not have a statistically difference (p>0.05). Clinical response rate to the combination arm was higher than the Gem arm (69.0% vs 49.7%, p=0.001). PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance (8.9 vs 6.0, p=0.08). OS was not significantly superior in the GemCis arm (12.0 vs 10.2, p>0.05). Grade III-IV hematologic and nonhematologic toxicity were higher in the combination arm. PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance. OS was not significantly superior in the GemCis arm.

Trabectedin in advanced soft tissue sarcoma: case series.

The prognosis of advanced soft tissue sarcomas (STS) is poor. The median overall survival (OS) is 6 months in unresectable and metastatic STS that progress after treatment with anthracyclines and ifosfamide. Trabectedin is an alkylating agent, effective in advanced STS, especially in leiomyosarcoma and liposarcoma. In the present study, the effectiveness and safety of trabectedin was retrospectively evaluated in 8 unresectable and metastatic STS patients. Their median age was 47 years. The median progression free survival (PFS) was 3.75 months and the median OS 15 months in relapse or progression after anthracyclines and/or ifosfamide. Toxicities were mainly hematologic. In the present study, trabectedin showed efficacy in different histological subtypes of sarcomas like liposarcoma and leiomyosarcoma.

Long term experience in high grade glial tumors with temozolomide.

PURPOSE: Temozolomide is used concurrently with radiotherapy (RT) and as consolidation therapy in high grade gliomas (HGGs). In the present study we present our experience of long-term efficacy and toxicity of temozolomide in HGGs. METHODS: After surgery, temozolomide was administered at 75 mg/m(2) daily concurrently with RT, followed by 6 courses of consolidation therapy (150-200 mg/m(2) for 5 days every 28 days). RESULTS: A total of 172 patients with either glioblastoma multiforme (GBM) (n= 142; 82.6%) or anaplastic astrocytoma (AA) (n= 30; 17.4%) were studied. The objective response rate (ORR) was 42.5%, including 12 (7%) complete responses (CRs) and 61 (35.5%) partial responses (PRs). In the GBM group, median progression free survival (PFS) and overall survival (OS) were 9 and 16 months, respectively. In the AA group, median PFS and OS were 16 and 24 months, respectively. Three-year OS was 18.2% for GBM, and 39.4% for AA. In elderly patients (14.5%), median PFS and OS were 8 and 11 months respectively for both HGGs. Serious toxicities were mainly hematologic. CONCLUSION: Temozolomide is an effective agent in HGGs with favorable outcome and low toxicity profile even in advanced age.

Hypoxia inducible factor-1 alpha and carbonic anhydrase IX overexpression are associated with poor survival in breast cancer patients.

PURPOSE: Hypoxia is common in many solid tumors such as breast, head-neck, and soft tissue malignancies. Hypoxia causes overexpression of hypoxia inducible factor-1 alpha (HIF-1α) and carbonic anhydrase IX (CA IX) which are associated with unfavorable prognosis in breast cancer. In our study, we evaluated HIF-1α and CA IX expression in patients with breast cancer. METHODS: Between June 1996 and June 2008, 111 women with breast cancer were evaluated. Estrogen receptor (ER) and progesterone receptor (PR) status and Her2/ neu expression were evaluated by immunohistochemical methods. Her-2/neu expression was also assessed by FISH method when needed. Two groups were created: ER and PR positive, Her-2/neu negative (group 1, n=56); and ER and PR negative, Her-2/neu positive (group 2, n=55). HIF-1α and CA IX expressions were investigated in both groups and results were compared. In addition, we investigated the association between HIF-1α and CA IX expressions with stage, grade, lymph node metastasis, tumor size, menopause status and survival. RESULTS: Median patient age in group 1 was 52 years (range 34-77), and in group 2 47 years (range 27-83). HIF-1α expression was detected in 26 (46.4%) of group 1 and in 46 (83.6%) of group 2 patients (p=0.0001). CA IX expression was detected in 25 (46.4%) of group 1 and in 37 (67.3%) of group 2 patients (p7equals;0.0137rpar;. In group 1, median disease free survival (DFS) was 97 months and in group 2 46 months (p=0.0308). In group 1, median overall survival (OS) was 108 months and in group 2 75 months (p=0.0339). CONCLUSION: HIF-1α and CA IX overexpressions are observed more often in ER and PR negative, Her-2/neu positive breast cancer and are associated with poor survival.

Multiple primary malignant neoplasms: multi-center results from Turkey.

PURPOSE: Multiple primary malignant neoplasms (MPMNs) are defined as a diagnosis of two or more indepen-dent primary malignancies of different histologies/origins in an individual. The frequency of MPMN is being increasing. In this study we aimed to determine the frequency and clinical features of second primary cancers (SPCs). METHODS: From January 1990 to December 2010, patients with MPMNs were screened in 5 centers. Data were obtained retrospectively from hospital charts. RESULTS: Three hundred seventy-seven patients with MPMNs were evaluated. The median age at initial cancer diagnosis was 61 years (range 18-88). The median age at second cancer was 64 years (range 20-89). The median time between two cancer diagnoses was 15 months (range 0-504). Male to female ratio was 1.44 (M/F 223/154). The most frequent initial cancer types were head and neck (54 patients, 14.3%), breast (54 patients, 14.3%), and colorectal (43 patients, 11.4%). The most frequent second cancer types were lung (76 patients, 20.2%), colorectal (39 patients, 10.3%) and breast (33 patients, 8.8%). The most common cancer pairs in females were breast-gynecologic cancers (15 patients, 9.7%), colorectal-breast cancers (9 patients, 5.8%) and breast-colorectal cancers (7 patients, 4.5%). The most common cancer pairs in males were head and neck-lung cancers (29 patients, 13%), bladder-lung cancers (9 patients, 4%), and bladder-prostate cancers (7 patients, 3%). The median follow up was 36 months (range 17horbar;595). CONCLUSION: Physicians should be aware of SPCs probabilities. Newly developed suspicious lesions should be evaluated rigorously. Histopathologic evaluations of suspicious lesions for second tumors should be used extensively if needed. In our series, the most common pairs were breast-gynecologic cancers in females and head and neck-lung cancers in males.

Prognostic factors in patients with advanced pancreatic cancer treated with gemcitabine alone or gemcitabine plus cisplatin: retrospective analysis of a multicenter study.

PURPOSE: The majority of patients with pancreatic cancer present with advanced disease. Systemic chemotherapy for patients with pancreatic cancer has limited impact on overall survival (OS). Patients eligible for chemotherapy should be selected carefully. The aim of this study was to analyse prognostic factors for OS in advanced pancreatic cancer patients treated with first-line palliative chemotherapy with gemcitabine alone or gemcitabine plus cisplatin. METHODS: We retrospectively reviewed 343 locally advanced or metastatic pancreatic cancer patients who were treated with gemcitabine or gemcitabine plus cisplatin as first-line chemotherapy between December 2000 and June 2011. Fifteen potential prognostic variables were chosen for analysis. Univariate and multivariate analyses were conducted to identify prognostic factors associated with OS. Univariate and multivariate statistical methods were used to determine prognostic factors. RESULTS: Among the 15 variables of univariate analysis, 6 were identified to have prognostic significance: stage (p<0.001), cholestasis (p=0.02), weight loss, prior pancreatectomy, serum CEA level (p<0.001) and serum CA19-9 level (p>0.001). In addition, age, chemotherapy and liver metastasis were of borderline significance (p=0.06). Multivariate analysis (Cox proportional hazard model) included the 6 significant prognostic factors of univariate analysis and showed that stage was independent prognostic factor for OS, as were weight loss, and serum CEA level. CONCLUSION: Stage, weight loss, and serum CEA level were identified as important prognostic factors for OS in advanced pancreatic cancer patients. These findings may also facilitate pretreatment prediction of OS and can be used for selecting patients for treatment.

Serum granulocyte colony-stimulating factor levels in gliomas.

PURPOSE: Apart from its known effects on granulopoiesis, granulocyte-colony stimulating factor (G-CSF) is also involved in growth and progression of malignant cells. In this study we report the serum G-CSF levels and their relationship with survival in patients with glial cell tumors. METHODS: Serum G-CSF levels of 17 patients (10 male, 7 female, median age 55 years, range 19-75), with histologically proven glial cell tumors and of 17 sex- and age-matched healthy controls were assayed by enzyme-linked immunosorbent assay (ELISA). RESULTS: All patients were treated with radiotherapy and concomitant temozolomide, followed by temozolomide alone. Eight patients were treated with carboplatin plus cyclophosphamide combination as second-line chemotherapy. The median follow-up was 21 months (4-42). The median OS was 36 months (95% CI, 15.7-56.4). Serum G-CSF levels in glioma patients and healthy controls were 44.14 ± 18.89 pg/ ml and 28.84±15.65 pg/ml, respectively (p=0.027). There was no significant correlation between survival time and serum G-CSF levels (r=0.384; p=0.217). CONCLUSION: Serum G-CSF levels were high in glioma patients compared with healthy controls and they may be involved in tumor progression, but the G-CSF role in prognosis was not clarified. Further studies with larger numbers of patients must be conducted to elucidate the role of G-CSF in glial cell tumors.

Mitomycin-C in combination with fluoropyrimidines in the treatment of metastatic colorectal cancer after oxaliplatin and irinotecan failure.

PURPOSE: To retrospectively evaluate the efficacy and tolerability of mitomycin-C (MMC) in combination with fluoropyrimidines as salvage 3rd -or 4th-line therapy in metastatic colorectal cancer (MCRC) patients. METHODS: All patients in this study had previously failed oxaliplatin and irinotecan-based chemotherapy. Patients were treated with MMC (6 mg/m(2) intravenously/i.v.) on day 1 in combination with either oral UFT (500 mg/m(2)) and oral leucovorin (LV) (30 mg) on days 1-14 every 3 weeks (group A) or infusional 5-fluorouracil (5-FU) by deGramont regimen with i.v. LV (200 mg/m(2)) on days 1 and 2, every 2 weeks (group B). RESULTS: Thirty-nine MCRC patients were analyzed. Twenty-two of them were in group A and 17 in group B. Thirty-three were evaluable for clinical efficacy. The clinical benefit in the intent-to-treat (ITT) population was 30.8%. Median progression free survival (PFS) was 6 months (95% confidence interval/ CI 4-8) and median overall survival (OS) 9 months (95% CI 6.5-11.5). Median PFS was 3 months (95% CI 2.4-3.6) in group A and 7 months (95% CI 5.1-8.9) in group B (p=0.009). Median OS was 7 months (95% CI 4.3-9.7) in group A and 12 months (95% CI 5.4-18.6) in group B (p=0.422). The combination of MMC and fluoropyrimidines was generally well tolerated. The most common severe toxicities were nausea and vomiting, neutropenia, hepatotoxicity and diarrhea. CONCLUSION: MMC in combination with fluoropyrimidines is safe and active in heavily-pretreated MCRC patients. This combination remains a viable option in these patients. However, better therapies are urgently needed.

Efficacy and toxicity of preoperative chemotherapy with docetaxel and epirubicin in locally advanced invasive breast cancer.

PURPOSE: To investigate the efficacy and safety of neoadjuvant chemotherapy with docetaxel plus epirubicin with granulocyte colony-stimulating factor (G-CSF) support in locally advanced breast cancer patients. METHODS: We retrospectively evaluated the records of 39 patients with locally advanced breast cancer. All of them received neoadjuvant epirubicin 75 mg/m(2) plus docetaxel 75 mg/m(2) every 3 weeks with G-CSF support. Responding patients were subjected to breast-conserving or modified radical mastectomy. RESULTS: Four (10.3%) patients achieved clinical complete response (cCR) and 25 (64.1%) clinical partial response (cPR). Pathologic complete response (pCR) was observed in 4 patients with cCR. Ten (25.6%) patients achieved stable disease (SD), while no patient had progressive disease (PD). Grade 3 and 4 neutropenia was observed in 6 (15.3%) and 4 cases (10.3%), respectively. Febrile neutropenia was observed in 2 (5.1%) cases and anemia in 7 (17.9%) cases. Grade 1/2 mucositis was observed in 12 (30.7%) patients and grade 1/2 peripheral neuropathy in 7 (17.9%) patients. Dose reduction was necessary in 4 patients with grade 4 neutropenia. The median disease-free survival was 60 months (95% CI: 41-79 months). Median overall survival was not reached. Five-year overall survival was 64.2%. CONCLUSION: The combination of docetaxel plus epirubicin was active and tolerable in neoadjuvant treatment of locally advanced breast cancer.

Intensive conditioning regimen of etoposide (VP-16), cyclophosphamide and carmustine (VCB) followed by autologous hematopoietic stem cell transplantation for relapsed and refractory Hodgkin's lymphoma.

Several high-dose therapy regimens are used for autologous hematopoietic stem cell transplantation (auto-HSCT) for relapsed and refractory Hodgkin's lymphoma (HL) with variable disease response. An intensified regimen of etoposide (VP-16) 2,400 mg/m(2), cyclophosphamide 7,200 mg/m(2) and carmustine (BCNU) 600 mg/m(2) (VCB) pre-auto-HSCT was developed to overcome disease recurrence. A total of 43 relapsed and refractory HL patients underwent auto-HSCT between January 1992 and December 2004. At day 100 there were 37 (86%) complete responses. A total of 40 patients survived beyond day 100, 14 of whom subsequently relapsed/progressed. At a median follow-up of 4.9 years (range 1.5-11.4 years), 26 patients (60%) are alive and disease free. Five-year actuarial event-free survival (EFS) was 53% (95% CI 35-70%) and median EFS was 5.9 years. Median progression-free and overall survivals have not been reached. EFS was reduced with an increasing number of prognostic factors (Karnofsky performance status, KPS <90, chemotherapy-resistant disease and >or=3 chemotherapy regimens prior to transplant or=2; P=0.049). Grade III-IV regimen-related toxicity was 9% (n=4). The 1-year cumulative incidence of interstitial pneumonitis (IP) was 36%, however only two patients died of IP complications. Disease progression was the most common cause of death (n=10, 23%). Intensive VCB is an effective and well-tolerated preparative regimen for relapsed and refractory HL auto-HSCT.

Xelox (capecitabine plus oxaliplatin) as neoadjuvant chemotherapy of unresectable liver metastases in colorectal cancer patients.

Complete resection of liver metastasis may provide long term survival in patients with colorectal cancer. Increased number of studies on successful resection after neoadjuvant chemotherapy with initially unresectable liver metastasis has been reported. We evaluated retrospectively the results of 35 patients with unresectable liver only metastases from colorectal cancer treated with capecitabine plus oxaliplatin combination (XELOX). Treatment consisted of IV oxaliplatin 130 mg/m2 day 1 and oral capecitabine 1000 mg/m2 day twice daily on days 1 to 14 followed by 7 days of rest repeated every 3 weeks. After chemotherapy, 13 (37, 2 %) patients showed partial clinical response. Among them, 7 patients were considered suitable for surgery but 2 patients refused the surgery. While one of 5 patients had unresectable disease at surgery, the remaining 4 patients (11, 4 %) had a complete resection. There was one postoperative mortality due to sepsis within 2 months after surgery. Our data suggests that XELOX regimen seems to be useful in unresectable liver only metastases from colorectal cancer because of its activity, feasibility and tolerability. Further studies of XELOX in combination with bevacizumab and/ or cetuximab are warranted in this setting.

Intrasellar plasmacytoma: an unusual presentation of multiple myeloma.

INTRODUCTION: Plasmacytomas are unusual causes of a sellar mass. Occasionally, they can be misdiagnosed as a nonfunctioning adenoma because of radiological and clinical similarities. LITERATURE REVIEW: We reviewed the pertinent literature and discuss here in the light of an illustrative case of our own. DISCUSSION: A 70-year-old woman presented with a recurrent hypophysial mass. Initial diagnosis of a nonfunctioning pituitary adenoma was later overruled by a repeat biopsy, which showed a plasmacytoma. The tumor stained positively for CD138 and kappa light chain. Further studies confirmed the diagnosis of multiple myeloma. The patient was successfully treated with radiotherapy followed by systemic chemotherapy. Because they have different therapeutic implications, extramedullary plasmacytomas involving pituitary gland should be considered in the differential diagnosis of a nonfunctioning pituitary mass.

GATA3 expression and its relationship with clinicopathological parameters in invasive breast carcinomas.

GATA3, as a transcription factor, is associated with estrogen receptor (ER) expression and necessary for luminal cell differentiation in mammary glands. Association of GATA3 expression with clinicopathological parameters, molecular subtypes of tumors, disease free survival (DFS) and overall survival (OS) for breast carcinoma patients were evaluated in this study. We immunohistochemically stained GATA3, CK5/6, EGFR, CK14 and vimentin on tissue microarray blocks of 457 invasive breast carcinomas. Tumors are sub-classified as luminal A, luminal B, HER2 expressing, basal-like and null type according to their hormonal status with cerbB2, CK 5/6 and EGFR expressions. Follow-up data for 254 cases were obtained. 215/457 (47%) tumors were GATA3 positive. GATA3 expression was inversely correlated with mitotic count (p<0.0001), nuclear grade (p=0.001), histological grade (p=0.001), tumor necrosis (p=0.001), stromal lymphocytic response (p<0.01), nipple invasion (p=0.01), metastasis (p=0.03), vimentin (p=0.0003), EGFR (p=0.015) and CK14 (p=0.001) expressions; and directly associated with ER (p<0.0001) and progesterone receptor (PR) (p<0.0001) expressions. Luminal A carcinomas had the highest frequency for GATA-3 (140/245), however basal-like carcinomas had the lowest (1/42) (p<0.0001). None of the medullary and metaplastic carcinomas expressed GATA3. GATA3 was associated with good DFS and OS (p=0.001 and p=0.0009) and was an independent prognostic factor for OS. GATA3 expression, regardless of the subtype, may have a prognostic significance for breast carcinomas through its ability to promote the differentiation of luminal progenitor cells.

Muromonab-CD3 (Orthoclone OKT3), methylprednisolone and cyclosporine for acute graft-versus-host disease prophylaxis in allogeneic bone marrow transplantation.

We report the results of a prospective non-randomized phase II study of Muromonab-CD3 (Orthoclone OKT3), an anti-CD3 monoclonal antibody, with methylprednisolone (MP) and cyclosporine (CSA) for acute GVHD (aGVHD) prophylaxis in 22 hematologic malignancy patients. OKT3 was given at 0.1 mg/kg/day with a maximum dose of 5 mg/day. Initial MP dose was 1000 mg before OKT3, with subsequent doses at 1 mg/kg/day before each OKT3 infusion with a planned taper beginning at day +28. CSA (3 mg/kg/day) was given as a continuous infusion at day -1 and adjusted to maintain serum levels between 250 and 399 ng/ml. Allogeneic BMT donors were HLA-matched siblings (n = 17), single HLA-mismatched-related (n = 1) and HLA-matched unrelated (n = 4). All patients achieved neutrophil engraftment at a median 11 days (range, 8-25 days). By intent-to-treat, the cumulative incidence of grade II-IV aGVHD was 33% (95% CI 13-53%) at a median 26 days post-BMT (range, 14-84 days). Chronic GVHD developed in 11/12 evaluable patients. Eight patients (36%) developed OKT3 first dose reactions; no cases of post-transplant lymphoproliferative disorder were observed. OKT3 depleted peripheral CD3+ cells in vivo as measured by flow cytometry. OKT3+MP+CSA combination is moderately effective aGVHD prophylaxis, however, it is unlikely to be superior to CSA+MTX.

A prognostic model for prolonged event-free survival after autologous or allogeneic blood or marrow transplantation for relapsed and refractory Hodgkin's disease.

There are several prognostic models for Hodgkin's disease (HD) patients, but none evaluating patient characteristics at time of blood and marrow transplantation (BMT). We developed a prognostic model for event-free survival (EFS) post-BMT based on HD patient characteristics measured at the time of autologous (auto) or allogeneic (allo) BMT. Between 1/1991 and 12/2001, 64 relapsed or refractory HD patients received an auto (n=46) or allo (n=18) BMT. A multivariate prognostic model was developed measuring time to relapse, progression or death. Median follow-up was 51.7 months; median EFS for auto and allo BMT was 36 and 3 months, respectively (P=0.001). Significant multivariate predictors of shorter EFS were chemotherapy-resistant disease, KPS <90 and > or =3 chemotherapy regimens pre-BMT. Patients with two to three adverse factors had significantly shorter EFS at 2 years (58 vs 11% in auto; 38 vs 0% in allo BMT patients). Despite a selection bias favoring auto BMT, the model was valid in both auto and allo BMT groups. We were able to differentiate patients at high vs low risk for adverse outcomes post-BMT. This prognostic model may prove useful in predicting patient outcomes and identifying high-risk patients for novel treatment strategies. Validation of this model in a larger cohort of patients is warranted.

Severe respiratory depression after dimethylsulphoxide-containing autologous stem cell infusion in a patient with AL amyloidosis.

Adverse reactions with DMSO-cryopreserved stem cell infusion are well-recognized. However, severe, life-threatening anaphylactic reactions with DMSO are very rarely described in the literature. We report here a 58-year-old female with AL amyloidosis who developed an unexpected episode of respiratory arrest a few seconds after the beginning of thawed stem cell product infusion. Fortunately, the patient was resuscitated successfully without the need for intubation. The prompt development of the reaction just a few seconds after the stem cell infusion convincingly implicates DMSO as the potential suspect. The presence of amyloid cardiomyopathy might have also contributed to this adverse event. Bone Marrow Transplantation (2000) 25, 1299-1301.

Effect of rituximab on peripheral blood stem cell mobilization and engraftment kinetics in non-Hodgkin's lymphoma patients.

Rituximab is used for in vivo tumor cell purging for non-Hodgkin's lymphoma (NHL) patients prior to autologous peripheral blood stem cell transplantation (PBSCT). However, its effects on PBSC mobilization and function are poorly understood. We compared the mobilization characteristics and engraftment kinetics of 13 NHL patients receiving and 34 NHL patients not receiving rituximab 6 months before PBSC mobilization. In the rituximab group, there was a significantly longer time to neutrophil engraftment (P=0.0466), a trend toward the need for BM harvest to supplement low-yield PBSC collections (31 vs 9%, P=0.08) and a significantly increased rate of bacteremia episodes (62 vs 26%, P=0.025). Median progression-free survival (PFS) and overall survival (OS) were significantly longer in the rituximab compared to the nonrituximab patients (P=0.049 and 0.042, respectively). However, patients in the nonrituximab group were at high risk for recurrence and expected to have shorter survival. Rituximab used within 6 months prior to collection may have a detrimental effect on PBSC mobilization and engraftment. However, rituximab is a major therapeutic breakthrough for NHL treatment and this negative effect may be offset by improved survival. Further studies are warranted in larger populations to determine the impact of rituximab on engraftment, PFS and OS.

Acute tumor lysis syndrome following intrathecal methotrexate.

We report a 17-year-old boy with meningeal involvement of lymphoblastic lymphoma who experienced acute tumor lysis syndrome following intrathecal administration of methotrexate. Intrathecally injected methotrexate provides a slow- release reservoir of methotrexate into the bloodstream with prolonged cytotoxic levels. To the best of our knowledge, this is the second case of tumor lysis syndrome to be described after intrathecal methotrexate injection. The pathogenesis of this unusual complication of intrathecal chemotherapy is discussed.