HAART Does Not Improve the Outcome of HIV-Related Multicentric Castleman Disease: Results of a Multicentric Retrospective Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4918-4918 ◽  
Author(s):  
Chiara Cattaneo ◽  
Emanuela Vaccher ◽  
Alessandro Re ◽  
Salvatore Casari ◽  
Erika Borlenghi ◽  
...  
Keyword(s):  
Median Time ◽  
Conflicts Of Interest ◽  
Primary Effusion Lymphoma ◽  
Case Series ◽  
Central Nervous System Lymphoma ◽  
Castleman Disease ◽  
Time Interval ◽  
Female Ratio ◽  
Multicentric Castleman Disease

Abstract Abstract 4918 Background. Multicentric Castleman Disease (MCD) is a rare lymphoproliferative disorder, strictly related to Kaposi Sarcoma (KS) as both associated to HHV-8 infection. Like other HIV-related diseases, such as Non Hodgkin Lymphoma (NHL) and Primary Central Nervous System Lymphoma, MCD prevalence is known to be increased in HIV-pos subjects. However, limited case series among this subset of patients (pts) are reported and data regarding epidemiological variations in the pre and post HAART era are often non conclusive. In order to evaluate possible differences between pre- and post-HAART era, we retrospectively evaluated epidemiological and clinical characteristics of all pts affected by HIV-pos MCD afferent to two Italian Institutions. Patients and Methods. Data concerning biological, clinical and prognostic factors of HIV-pos MCD pts were collected and reported on a database. Pts were grouped according to the date of diagnosis in pre- (before 1997) and post-HAART (after 1997) era. Results. During a 21-year period (1990-2011), 35 HIV-pos MCD pts were observed at our Institutions, nine in the pre- and 26 in the post-HAART era. Male/Female ratio was 30/5; median age 37y (23-65). Histological subtype in 34 evaluable cases was hyaline-vascular in 6, plasmacytic in 20 and mixed cellularity in 8. Median time interval from HIV-pos detection to MCD diagnosis was 24 months (range 0–157) and CD4 count at MCD diagnosis 233/mcL (26-839). All these MCD baseline characteristics were not statistically different between pre- and post-HAART era. A concomitant diagnosis of KS was made in 18/35 (51.4%) cases, all but one in the post-HAART era. NHL was diagnosed concurrently with MCD in 2/35 (5.7%) pts (1 Primary Effusion Lymphoma, PEL, and 1 Plasmablastic Lymphoma, PBL); in 8/35 (22.8%) cases NHL developed after MCD diagnosis (2 PEL, 1 PBL, 2 Diffuse Large Cell, DLC, 1 unspecified, respectively). Median time from MCD to NHL was 19 mo (0-71). Evolution toward NHL was observed in 3 (33%) cases in the pre-HAART era and in 5 (19%) in the post-HAART era (p=0.39, Fisher's exact test). Six pts did not receive any type of treatment, 6 were treated with HAART only and 23 with different therapies, including antivirals, steroids, chemotherapy and rituximab (alone in 1 pt, in combination with chemotherapy in 5). Nineteen/23 pts received HAART together with other therapies. Two pts treated with rituximab developed NHL (1 PEL and 1 DLC). A complete or partial radiological response, together with clinical improvement was observed in 19/25 of evaluable pts (76%). Thirty pts were evaluable for relapse/progression, mainly in the post-HAART era. Overall, 19/30 pts showed MCD progression or transformation to NHL; median PFS was 15 months. Nineteen pts died and 5 were lost to follow-up. Overall survival (OS) of the entire series was 28 months, without significant differences between pre and post-HAART era (18 and 28 months, OR 0.643 [CI 0.2406–1.045], median follow-up 18 and 9 months, respectively). Causes of death were evaluable in 18 cases: NHL (7), MCD (6), opportunistic infections (1), liver cyrrhosis (1), acute myocardial infarction (1), KS (1) and therapy-related toxicity (1). NHL and MCD were the most frequent cause of death in the post-HAART era (4 and 5 of the 10 cases, respectively). Although no differences in OS between MCD pts without or with NHL were seen (19 vs 28 months, OR 0.6786 [CI 0.2763–1.081], median follow-up 13 and 23 months, respectively), eight/10 pts with NHL died, in comparison with 11/21 pts without NHL evaluable for outcome and median time from NHL diagnosis to death was 2 months (0-31). Conclusions. Our data confirm that the prognosis of HIV-related MCD remains poor even after the advent of HAART. Unlike other lymphoproliferative disorders, HAART did not impact on outcome of HIV-related MCD, suggesting that MCD can “escape” immune reconstitution. A concomitant diagnosis of NHL and uncontrolled MCD seem to be the main reason for an unfavourable outcome, particularly in the post-HAART era. New therapeutic approaches, including rituximab, should therefore aim at avoiding NHL transformation and controlling “MCD-related cytokine storm”. Disclosures: No relevant conflicts of interest to declare.

Rituximab, Endoxan, Ganciclovir, Dexamethasone, Tocilizumab Sequential Treatment In Kaposi's Sarcoma-Associated Herpesvirus (KSHV) -Related Multicentric Castleman Disease. A Case Report with 8 Months Follow-up

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4872-4872
Author(s):  
Francesco Iuliano ◽  
Tecla Mingrone ◽  
Stefania Infusino ◽  
Alessia Perricelli ◽  
Angelo Pomillo ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Sequential Therapy ◽  
Clinical History ◽  
Castleman Disease ◽  
High Grade Fever ◽  
Intravenous Ganciclovir ◽  
Multicentric Castleman Disease ◽  
First Case ◽  
History Of

Abstract Abstract 4872 Clinical history of Kaposi sarcoma-associated herpesvirus (KSHV),-related Multicentric Castleman Disease is characterized by a rapidly progressive and often fatal course. We report a case successfully treated sequentially with a course of 4 infusions of rituximab 375mg/m2 at weekly intervals, Endoxan, 750 mg/m2 as an intravenous infusion once weekly for 2 weeks, intravenous ganciclovir, 5 mg/kg twice daily for 2 weeks and then once daily, dexamethasone 20 mg on days 1–4, 9–12, 17–20 and anti-interleukin-6 receptor antibody (tocilizumab) administered intravenously at a dose of 8 mg/kg every 2 weeks, starting at day 32. On December 12, 2009, a 54-year-old man came to the medicine department because of a 2-week history of progressive fatigue, wasting, high-grade fever (39°C), profuse sweating, and severe autoimmune hemolytic anemia (4.2 mg/dL). He had been diagnosed with asymptomatic MCD 6 months before admission. Generalized lymphadenopathy and hepato-splenomegaly were evident on physical examination and enlarged lymph nodes in retroperitoneal regions (CT scan). Blood biochemistry showed very high CRP, IL-6, beta 2 microglobulin serum levels, low LDH and albumin, increase polyclonal immunoglobulin, grade 3 thrombocytopenia and neutropenia. Serologic tests (Epstein-Barr virus, hepatitis B and C viruses, cytomegalovirus and human immunodeficiency virus) were negative. On hospital day 10, 250.000 copies of HHV-8 DNA were detected in 1 mL plasma by RT-PCR. The patient achieved CR two months after admission, still maintained at 8 month follow-up. HHV-8 DNA became undetectable over the course of 8 weeks, at which time ganciclovir was discontinued. Conclusions: In our case the onset of the disease was serious and life-threatening. Sequential therapy has proven to be able to save the life of the patient acting on different biological targets. To date is the first case treated with this schedule. Disclosures: No relevant conflicts of interest to declare.

Determining Late Engraftment Following Single Cord, Unrelated Transplantation: An Analysis of the Eurocord Registry

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 650-650
Author(s):  
Riccardo Saccardi ◽  
Myriam Labopin ◽  
Annalisa Ruggeri ◽  
Chantal Kenzey ◽  
Wagnara Chaves ◽  
...  
Keyword(s):  
Median Time ◽  
Cumulative Incidence ◽  
Prolonged Exposure ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Clinical Problem ◽  
Clinical Decision ◽  
Time Interval ◽  
Maximum Probability

Abstract Abstract 650 INTRODUCTION. The most prominent clinical problem in CB transplant is a slower engraftment kinetic, as compared to the conventional SC sources. Engraftment failure is usually defined in CB transplantation as a lack of PMN recovery 60 days after transplant, whilst a definition of late engraftment is currently lacking. A late engraftment is a major cause of transplant-related mortality (TRM), due to the prolonged exposure of the recipient to the infective and hemorrhagic risk. After the HSCT, the probability of engraftment at each time interval tends to increase up to a maximum and then gradually decreases, which is typically represented by a sinusoid curve. The decrease of engraftment probability after transplant results in a rapidly increasing risk of TRM; therefore such a turning point should be considered the beginning of a risk phase for late/no engraftment. Therefore, it is important to find the time point after UCBT in which the probability of engraftment will decrease in order to help taking a decision for rescue with a second transplant. We analyzed the clinical expectations beyond this time in a homogenous population of CB recipients. PATIENTS AND METHODS. We investigated the engraftment kinetic in a population of 1215 patients who received a single, unrelated CB transplant for Acute Leukemia (AL) in Complete Remission (CR) following a Myeloablative Conditioning Regimen (MAC). All patients were transplanted in EBMT Centers and reported to the Eurocord Registry from 1994 to 2010. Ratio Lymphoid/Myeloid Leukemias was 769/445, reflecting a major proportion of pediatric patients over adults (857/357). Patients were transplanted in first (43.4%), second (46,6%), or third or subsequent remission (10%), respectively. Median (range) age at transplant was 9.5 (0.3-63) years. Median weight (Kg) at transplant was 33 (5-112). Out of 1089 patients evaluable for HLA-matching, 601 (55.2%) were mismatched for 0–1 loci, 448 (41.1%) for 2 loci and 40 (3.6%) for more than 2 loci. Fifty percent of the patients had a TBI-based myeloablative regimen. Data on TNC counts at freezing of transplanted CBU were available in 963 cases: median and range were 5 (1.1-41.83)x107/Kg. RESULTS. The median FU was 30 months (1-174). At 24 months overall survival was 49±2%, TRM was 32±2%. Median time of engraftment was 24 days (10-133) with a cumulative incidence of 86±1% at day 60. Analyzing the cumulative curve of engraftment, we considered the engraftment probability within intervals of five days after the transplant; in fact the highest probability of engraftment was at day 25 and dropped of 50% at day 42. Among 167 patients (13.7%) who did not engraft at this time, 63 patients (38%) experienced a late engraftment with a median time of 47 days (43-131) after transplant. The cumulative incidence of engraftment at 120 days was 37% and 38% at day 180 without any further increasing later on. Out of the 104 patients who never engrafted, 74 died and major causes of death were bacterial (17%), viral (10%) and fungal (9%) infections, respectively, whilst 30 patients are alive at the last follow up. Information of graft failure treatment was available for 84 patients. Twenty eight did not receive any treatment (25 died at a median time of 80 days form UCBT), 24 had an autologous back up and 32 underwent a second allogeneic HSCT (14 second UCBT, 9 Haplo PBSC and 9 unrelated BMT). Of those 32, 17 patients engrafted, 5 relapsed; 24 died, 8 are alive at last follow up. CONCLUSIONS: The maximum probability of engraftment after UCBT for patients with AL in remission is at day 25 and halves at day 42, thus suggesting that a clinical decision should be made within this period. In particular, rescue actions, such as infusion of another graft, either allogeneic of autologous, should be considered. Such a model can be applied to different subsets of patients and is particularly useful in transplant at high risk of late engraftment such as UCBT. Disclosures: No relevant conflicts of interest to declare.

Clinical Presentation, Treatment and Outcome of HIV-Associated Multicentric Castleman Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3897-3897
Author(s):  
Musa Alzahrani ◽  
Mark C Hull ◽  
Christopher Sherlock ◽  
Deborah Griswold ◽  
Chantal S Leger ◽  
...  
Keyword(s):  
Clinical Presentation ◽  
Conflicts Of Interest ◽  
Primary Effusion Lymphoma ◽  
Age At Onset ◽  
Tumor Lysis Syndrome ◽  
Castleman Disease ◽  
Cd4 Count ◽  
Human Herpes Virus 8 ◽  
Multicentric Castleman Disease

Abstract Abstract 3897 Background: Multicentric Castleman disease (MCD) is a monotypic but non-clonal lymphoproliferation with increased incidence in HIV infection. It is characterized by human herpes virus 8 (HHV-8) infection of the lymphocytes. Signs and symptoms (sx) are largely mediated by HHV-8 induced production of IL-6. Although life expectancy in MCD appears to have improved in the era of highly active antiretroviral therapy (HAART), it remains poor, and the optimal treatment approach in patients (pts) not responding to HAART is undefined due to few large series in which to evaluate management. Contributing to poor outcome is a concomitant increased incidence of other HHV-8 related disorders such as Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL), particularly primary effusion lymphoma and plasmablastic lymphoma (PBL). We report the clinical presentation, treatment and outcome of 8 pts with HIV associated MCD diagnosed and treated at our center since 2005. Methods: Pts with HIV-associated MCD were identified from the clinical database of the hematology practice. Charts were reviewed and the following data was extracted: baseline characteristics such as prior opportunistic infections or neoplasms, HAART received and response (CD4 count, HIV viral load [VL]), clinical and laboratory features (including HHV-8 in tissues and plasma HHV-8 VL), MCD course as well as treatment and outcome. Results: Median age at onset of MCD sx was 43 (range 31–63) years (y) and all pts were male. HIV risk was men who have sex with men (MSM) in all and 1 pt had a history of KS. Seven pts were receiving HAART at MCD presentation and the median CD4 count was 385 (140-950) cells/mL and HIV VL 318 (<40-2080) copies/mL. The most common MCD presenting sx were: drenching sweats, n=7; fever, n=6; fatigue, n=4; shortness of breath, n=4; nausea, vomiting and diarrhea, n=3. Signs included: lymphadenopathy, n=8; splenomegaly, n=8; edema, n=4; ascites, n=3; hepatomegaly, n=3; jaundice, n=3; maculopapular rash, n=3; cutaneous KS, n=2. The most striking feature was the waxing and waning course in all pts. Pts were moderately to severely ill for up to several weeks (3 pts required ICU admission; total 6 episodes). Near complete recovery lasting up to several weeks followed after which signs and sx recurred. Common findings on investigation were: anemia, n=8; thrombocytopenia, n=7; hyperbilirubinemia, n=6; and interstitial pulmonary infiltrates, n=5. The median hemoglobin and platelet counts at MCD dx were 89 (67-114) G/L and 128 (34-199) × 109/L, respectively, and 4 pts each required transfusion support. MCD dx was made in the presence of characteristic morphologic features and demonstration of tissue HHV-8 staining on biopsy (excisional lymph node, n=7; splenectomy, n=1; clinical probability plus HHV-8 plasma VL [7 ×106 HHV-8 copies/mL] with positive stains for HHV-8 in the bone marrow, n=1). The median interval from onset of MCD sx to diagnosis (dx) was 7.5 (2-13) months and the time to MCD dx following HIV dx was a median of 9 (0.2-20) y. Concomitant conditions were: KS, n=5 (limited to lymph nodes, n=3; extensive cutaneous, n=2); hemophagocytic lymphohistiocytosis (HLH), n=2; PBL, n=1; Henoch-Schonlein purpura (HSP), n=1. One or more plasma HHV-8 VL measurements were obtained in 5 pts, and 5 were started on valgancyclovir (VGCV) as anti-HHV-8 therapy with a 6th pre-treatment. The median follow-up from MCD dx is 2.6 (0.1-66) months. VGCV was well tolerated. One pt receiving VGCV after not responding to HAART sustained a long term remission of both MCD and KS and remains clinically well 6 y from the onset of sx (5.25 y from starting VGCV). One pt developed tumor lysis syndrome following the initiation of VGCV and is currently improving clinically, 3 are early in VGCV treatment (1-10 weeks). Two pts died, including the pt with PBL, before MCD could be confirmed and treatment started. Conclusions: MCD can be challenging to diagnose due to its waxing and waning nature and frequently poor accessibility of tissue for biopsy. Simultaneous diagnoses such as KS, NHL, HLH and HSP further compound these difficulties. Anti-HHV-8 therapy is a potentially promising treatment for MCD and possibly other HHV-8 mediated conditions, with a long term remission achieved in OUR first pt treated with VGCV. The diagnosis and management of MCD requires a multi-disciplinary approach. To our knowledge, this is one of the largest single institution experiences with HIV-associated MCD reported. Disclosures: No relevant conflicts of interest to declare.

scholarly journals KSHV- and EBV-associated germinotropic lymphoproliferative disorder

Blood ◽  
2002 ◽  
Vol 100 (9) ◽  
pp. 3415-3418 ◽  
Author(s):  
Ming-Qing Du ◽  
Tim C. Diss ◽  
Hongxiang Liu ◽  
Hongtao Ye ◽  
Rifat A. Hamoudi ◽  
...  
Keyword(s):  
Lymphoproliferative Disorder ◽  
Gene Rearrangement ◽  
Primary Effusion Lymphoma ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
Lymphoproliferative Disorders ◽  
Multicentric Castleman Disease ◽  
Tissue Sections ◽  
Response To Chemotherapy ◽  
Ig Heavy Chain

Abstract Kaposi sarcoma–associated herpesvirus (KSHV) is known to be associated with 3 distinct lymphoproliferative disorders: primary effusion lymphoma (PEL), multicentric Castleman disease (MCD), and MCD-associated plasmablastic lymphoma. We report 3 cases of a previously undescribed KSHV-associated lymphoproliferative disorder. The disease presented as localized lymphadenopathy and showed a favorable response to chemotherapy or radiotherapy. Histologically, the lymphoproliferation is characterized by plasmablasts that preferentially involved germinal centers of the lymphoid follicles, forming confluent aggregates. They were negative for CD20, CD27, CD79a, CD138, BCL6, and CD10 but showed monotypic κ or λ light chain. Clusters of CD10+CD20+ residual follicle center cells were identified in some of the follicles. The plasmablasts were positive for both KSHV and EBV, and most of them also expressed viral interleukin-6 (vIL-6). Unexpectedly, molecular analysis of whole tissue sections or microdissected KSHV-positive aggregates demonstrated a polyclonal or oligoclonal pattern of immunoglobulin (Ig) gene rearrangement. The plasmablasts showed somatic mutation and intraclonal variation in the rearranged Ig genes, and one case expressed switched Ig heavy chain (IgA), suggesting that they originated from germinal center B cells. We propose calling this distinctive entity “KSHV-associated germinotropic lymphoproliferative disorder.”

scholarly journals Latent KSHV infection increases the vascular permeability of human endothelial cells

Blood ◽  
2011 ◽  
Vol 118 (19) ◽  
pp. 5344-5354 ◽  
Author(s):  
Christophe Guilluy ◽  
Zhigang Zhang ◽  
Prasanna M. Bhende ◽  
Lisa Sharek ◽  
Ling Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Permeability ◽  
Latent Infection ◽  
Primary Effusion Lymphoma ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
Cell Junctions ◽  
Paracrine Factors ◽  
Kshv Infection ◽  
Multicentric Castleman Disease

Abstract Kaposi sarcoma–associated herpesvirus (KSHV) is associated with 3 different human malignancies: Kaposi sarcoma (KS), primary effusion lymphoma, and multicentric Castleman disease. The KS lesion is driven by KSHV-infected endothelial cells and is highly dependent on autocrine and paracrine factors for survival and growth. We report that latent KSHV infection increases the vascular permeability of endothelial cells. Endothelial cells with latent KSHV infection display increased Rac1 activation and activation of its downstream modulator, p21-activated kinase 1 (PAK1). The KSHV-infected cells also exhibit increases in tyrosine phosphorylation of vascular endothelial (VE)–cadherin and β-catenin, whereas total levels of these proteins remained unchanged, suggesting that latent infection disrupted endothelial cell junctions. Consistent with these findings, we found that KSHV-infected endothelial cells displayed increased permeability compared with uninfected endothelial cells. Knockdown of Rac1 and inhibition of reactive oxygen species (ROS) resulted in decreased permeability in the KSHV-infected endothelial cells. We further demonstrate that the KSHV K1 protein can activate Rac1. Rac1 was also highly activated in KSHV-infected endothelial cells and KS tumors. In conclusion, KSHV latent infection increases Rac1 and PAK1 activity in endothelial cells, resulting in the phosphorylation of VE-cadherin and β-catenin and leading to the disassembly of cell junctions and to increased vascular permeability of the infected endothelial cells.

Orbital Hydatid Cyst: An Interventional Case Series

2021 ◽  
Vol 37 (2) ◽  
Author(s):  
Tajamul Khan ◽  
Ibrar Hussain ◽  
Zaman Shah
Keyword(s):  
Visual Acuity ◽  
Hydatid Cyst ◽  
Teaching Hospital ◽  
Case Series ◽  
Surgical Excision ◽  
P Value ◽  
Presumptive Diagnosis ◽  
Female Ratio ◽  
Orbital Imaging

Purpose:  To find out the demographics, presentation, and outcome of surgical treatment in patients of orbital hydatid cyst. Study Design:  Interventional case series. Place and Duration of Study:  Khyber Teaching Hospital Peshawar, Pakistan from 2009 to 2019. Methods:  This study included 11 patients with orbital hydatid cyst who presented in Khyber Teaching Hospital, Peshawar. Detailed history, ocular examination and Orbital imaging (Ophthalmic B-Scan, CT scan and/or MRI) was performed. The patients underwent Orbitotomy, cyst extirpated and sent for histopathology. Albendazole was given to the patients for 12 weeks after surgery. The preoperative and postoperative data until last follow-up was analyzed. Results:  Male to Female ratio was 5:6 and the mean age of the patients was 18.17 ± 17.4 years. Mean amount of proptosis was 26.27 ± 2.05mm and visual acuity was 0.23 ± 0.33 decimal in the affected eye at presentation. Eight patients (72.8%) had Relative Afferent Pupillary Defect with swollen discs. After imaging studies, presumptive diagnosis of hydatid cyst was made. Histopathology confirmed the diagnosis of hydatid cyst in all cases. Mean proptosis at the last follow up improved to 19.04 ± 1.45mm (P value = 0.00) and visual acuity to 0.47 ± 0.22 decimals (P value = 0.048). Only one patient (9.1%) had an associated hydatid cyst in the lung. There was no recurrence until last follow-up. Conclusion:  Hydatid cyst should be considered in differential diagnosis of proptosis in patients under 20. Surgical excision followed by a course of oral Albendazole is effective for the treatment of orbital hydatid cyst. Key Words:  Orbital hydatid cyst, Proptosis, Orbitotomy.

Nonsyndromic craniosynostosis in Vietnam: initial surgical outcomes of subspecialty mentorship

2021 ◽  
pp. 1-8
Author(s):  
Dang Do Thanh Can ◽  
Jacob R. Lepard ◽  
Nguyen Minh Anh ◽  
Pham Anh Tuan ◽  
Tran Diep Tuan ◽  
...  
Keyword(s):  
Scale Up ◽  
Unmet Need ◽  
Case Series ◽  
Surgical Care ◽  
Cranial Vault ◽  
Female Ratio ◽  
Estimated Blood Loss ◽  
Common Diagnosis ◽  
Cranial Vault Remodeling

OBJECTIVE There is a global deficit of pediatric neurosurgical care, and the epidemiology and overall surgical care for craniosynostosis is not well characterized at the global level. This study serves to highlight the details and early surgical results of a neurosurgical educational partnership and subsequent local scale-up in craniosynostosis correction. METHODS A prospective case series was performed with inclusion of all patients undergoing correction of craniosynostosis by extensive cranial vault remodeling at Children’s Hospital 2, Ho Chi Minh City, Vietnam, between January 1, 2015, and December 31, 2019. RESULTS A total of 76 patients were included in the study. The group was predominantly male, with a male-to-female ratio of 3.3:1. Sagittal synostosis was the most common diagnosis (50%, 38/76), followed by unilateral coronal (11.8%, 9/76), bicoronal (11.8%, 9/76), and metopic (7.9%, 6/76). The most common corrective technique was anterior cranial vault remodeling (30/76, 39.4%) followed by frontoorbital advancement (34.2%, 26/76). The overall mean operative time was 205.8 ± 38.6 minutes, and the estimated blood loss was 176 ± 89.4 mL. Eleven procedures were complicated by intraoperative durotomy (14.5%, 11/76) without any damage of dural venous sinuses or brain tissue. Postoperatively, 4 procedures were complicated by wound infection (5.3%, 4/76), all of which required operative wound debridement. There were no neurological complications or postoperative deaths. One patient required repeat reconstruction due to delayed intracranial hypertension. There was no loss to follow-up. All patients were followed at outpatient clinic, and the mean follow-up period was 32.3 ± 18.8 months postoperatively. CONCLUSIONS Surgical care for pediatric craniosynostosis can be taught and sustained in the setting of collegial educational partnerships with early capability for high surgical volume and safe outcomes. In the setting of the significant deficit in worldwide pediatric neurosurgical care, this study provides an example of the feasibility of such relationships in addressing this unmet need.

Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) in Patients with Haematological Lymphoid Malignancies: Long Term Follow-up in a Single Centre Series.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4326-4326
Author(s):  
Malek Benakli ◽  
Redhouane Ahmed nacer ◽  
Amina Talbi ◽  
Rachida Belhadj ◽  
Farih Mehdid ◽  
...  
Keyword(s):  
Complete Remission ◽  
Hodgkin Lymphoma ◽  
Median Time ◽  
Conflicts Of Interest ◽  
Late Onset ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Lymphoid Leukaemia ◽  
Autologous Transplant

Abstract Abstract 4326 Background Patients (pts) with recurrent and refractory haematological lymphoid malignancy (HLM) have a very limited survival expectance. RIC allo-SCT has been proposed as a strategy for retaining the graft versus malignancy effect of allo-SCT while decreasing transplant related mortality (TRM). Here, we retrospectively studied a series of 32 pts treated by RIC allo-SCT. Patients and methods Between April 2001 and November 2007, 32 pts with HLM underwent RIC allo-SCT with an HLA-identical sibling donor. Fifteen pts with multiple myeloma, 7 pts with Non-Hodgkin lymphoma, 6 pts with Chronic lymphoid leukaemia, 3 pts with Hodgkin lymphoma and 1 pt with Waldenstrom disease. At time of allo-SCT, 10 pts were in complete remission (3 received prior autologous transplant) and 22 in refractory/progressive disease (6 received prior autologous transplant). Median age was 38 years (range, 28-60) and the sex-ratio (M/F) 2,2. Median time from diagnosis to RIC allo-SCT was 18 (range,6-76) months. The conditioning regimen included Fludarabine 150mg/m2 and Melphalan 140mg/m2. GVHD prophylaxis consisted of association cyclosporine (cSA) and mycophenolate (MMF). All pts received G-CSF mobilised peripheral blood stem cells, with a median CD34+ cell count: 6,2.106/kg (range, 1.9-13,6). Results Neutropenia occurred in all pts (100%) and the median duration of aplasia was 9 (range, 5-16) days. Only 10 pts (31 %) required red blood cells transfusions and 23 pts (71 %) needed platelets transfusions. Acute GVHD was observed in 15 cases (47 %) including 10 cases of grade II-IV. Fifteen pts (75 %) had chronic GVHD, of whom 9 with an extensive form. Four pts (12 %) had CMV reactivation at a median time 60 (range, 52-80) days after transplantation. Six pts (18 %) had late onset relapse at a median time of 13 (range, 4-45) months. TRM was 43 % at one year after RIC allo-SCT. With a median follow-up of 60 (range 18-97) months, 12 pts (37,5 %) are still alive in complete remission with full donor chimerism. Twenty pts (62,5 %) have died (5 early severe infections, 10 GVHD, 3 after relapse, one myocardial infarction, and one accident). Overall and progression-free survivals at 8 years are 31 % and 30 % respectively. Conclusion This study, after a large follow-up, suggests that RIC allo-SCT is a potential therapy for refractory or progressive HLM. However, TRM is still high likely due to the inclusion of refractory and heavily pretreated pts with many comorbid conditions. Disclosures: No relevant conflicts of interest to declare.

Efficacy of Lenalidomide-Based Regimens in Multiple Myeloma Complicated by Extramedullary Plasmacytomas at Relapse or Progression.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4952-4952 ◽  
Author(s):  
Jose Manuel Calvo-Villas ◽  
Adrian Alegre ◽  
Ricarda García-Sánchez ◽  
Miguel T Hernández ◽  
Pilar Giraldo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Median Time ◽  
Light Chain ◽  
Conflicts Of Interest ◽  
Bone Lesions ◽  
Complete Disappearance ◽  
Toxicity Profile ◽  
Small Series ◽  
Extramedullary Plasmacytomas

Abstract Abstract 4952 Background Current clinical observations on extramedullary myeloma (EM) are based on small series of relapsed myeloma patients (pts) and, in this situation, results suggest that the disease course is often aggressive. Among novel therapies for extramedullary involvement, thalidomide has provided poor results and bortezomib is emerging as a possible useful drug. The role of lenalidomide for treatment of multiple myeloma (MM) with EM is still under investigation. Aim A multicenter retrospective study was performed by PETHEMA (Spanish Myeloma Group, Spain) to evaluate the response rate and toxicity profile of lenalidomide-based regimens in myeloma patients with extramedullary involvement at relapse or progression. All the cases were evaluated for response of MM and improvement of extramedullary plasmacytoma. Patients and Methods From October 2007 to March 2009, thirteen patients (median age 67 years; range 61–87; 7 females) treated with lenalidomide-containing regimens were recorded. Patients with bone disease without extramedullary manifestations were excluded. Response of MM was evaluated according to the new international criteria and the response of EM by measuring size changes by physical examination, CT scans and/or MR imaging. Adverse events were graded based on the WHO toxicity scale. The M-protein type was IgG in 7 cases, IgA in 5 and light chain in 1. The type of light chain was κ in 7 pts and l in 6. In eight patients the soft-tissue plasmacytomas may have developed from underlying bone lesions [(skull (n=2), rib cage (n=4) and paravertebral (n=2)], two patients had subcutaneous nodules and three had visceral involvement (liver (n=1), lung and kidney (n=1) and pleura (n=1). Multiple localizations were present in 4 pts (30.7%). Six cases (79.6%) received previous antimyeloma treatment for EM before lenalidomide therapy and the incidence of prior bone plasmacytomas was 61.5%. Median time from initial antimyeloma therapy to treatment with lenalidomide was 34 months (range 5 - 115). Median number of prior lines of chemotherapy regimens was 3 (range 1 – 4), including autologous stem cell transplantation in 2 pts, bortezomib-containing regimens in 12 (92.3%) and previous exposure to thalidomide in 1 patient. Ten pts received standard lenalidomide dose (25 mg/day every 4 weeks) plus dexamethasone (40 mg/d PO ranging from 1 to 12 doses/cycle) every 3-week; and three patients received lower doses of lenalidomide and/or different schedules. Involved-field radiotherapy was given in 2 cases. Thirty percent of patients required lenalidomide dose reduction, because of toxicity or intolerance. Results Median duration of lenalidomide treatment was 3.6 months (1 – 15). One case was not evaluable for response because of death from disease progression after one cycle. In nine out of twelve evaluable patients (75%), MM responded to lenalidomide regimens according to EBMT criteria. Three (25%) achieved complete response, five (41.6%) partial response and 1 (8.3%) minimal response. Median time to response was 63 days (range 37 – 180). Regarding EM, nine patients showed response in the size of extramedullary plasmacytomas. Seven (58.3%) achieved complete disappearance of EM and two pts reduction of the size. Response of EM was also achieved in 75% of pts previously exposed to bortezomib, and in 4/9 cases who received therapies for prior extramedullary involvement. Median follow-up period was 6.3 months (1 – 15.8). Median overall survival from the start of lenalidomide therapy was 4.7 months. At the time of analysis, seven patients were still on therapy, and ten (76.9%) were alive. Only one out of the 9 patients who had achieved a response has relapsed so far. Toxicity profile (grade 3/4) was: thrombocytopenia, 4 (30.7%); anemia, 2 (15.3%); neutropenia, 5 (46.4%); neutropenic fever, 1 (7.6%) and others, 3 (11.8%). No deep venous thrombosis (DVT) was reported. Thrombosis prophylaxis was used in most cases (92%) patients. Conclusions We report one of the first investigations specifically evaluating the activity of lenalidomide on EM. Lenalidomide-containing regimens could be an alternative promising approach to achieve clinical response in heavily treated MM patients with extramedullary disease. The duration of response and the best regimen or combination are at present unknown. These preliminary observations require further analysis and longer follow-up. Disclosures No relevant conflicts of interest to declare.

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