Serial Serum Cytokine Measurement in a Patient with Systemic Scleromyxedema.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5100-5100
Author(s):  
Timothy Devos ◽  
Wouter Meersseman ◽  
Benedicte Dubois ◽  
Jozef Goebels ◽  
Gregor Verhoef ◽  
...  
Keyword(s):  
Plasma Cells ◽  
Serum Levels ◽  
Skin Lesions ◽  
Pulse Therapy ◽  
High Dose ◽  
Serum Samples ◽  
Hematopoietic Stem ◽  
Pre Treatment ◽  
One Year ◽  
High Dose Melphalan

Abstract Systemic scleromyxedema (SSME) is a generalized and rare variant of lichen myxedematosus and is characterized by cutaneous papular mucinous deposits and extracutaneous manifestations. In 80% of the cases, SSME is associated with a monoclonal gammopathy and in approximately 10% with multiple myeloma. Pulmonary, gastrointestinal, rheumatologic and severe neurologic complications have been described. Clonal plasma cells are thought to stimulate excessive fibroblast proliferation resulting in the clinical presentation of this disorder, but little is known about the cytokine-mediated crosstalk between the monoclonal plasma cells and fibroblasts. For that purpose, we have sequentially measured the serum levels of the cytokines VEGF, FGF-b, TGF-b1 and IL-6 in a 39-year old male patient diagnosed with SSME and an IgG kappa paraprotein. The patient presented with repeated generalized epileptic insults, cognitive impairment, and progressively developed thickened skin furrows at the level of the glabella. The diagnosis of SSME was histologically proven. A transient neurologic improvement was seen after plasmapheresis and dexamethason pulse therapy and stem cells were subsequently mobilized with the CAD regimen (cyclophosphamide, adriamycin, dexamethason) and readministered after high dose melphalan. The neutropenic phase was complicated by sepsis and progressive neurological deterioration, after which the decision was taken to start with thalidomide at the dose of 200 mg/d. The patient gradually improved and one year later his cognitive function has normalized and the skin lesions have disappeared. A small M-spike remains visible on serum electrophoresis. Levels of VEGF, FGF-b, TGF-b1 and IL-6 were quantified by ELISA on platelet-poor serum and were measured at diagnosis and at six and twelve months after transplantation. Compared to the high pre-treatment levels of all four cytokines, a decrease was observed during the months after transplantation and at six months. Table 1: serum levels of VEGF, b-FGF, TGF-b1 and IL-6 in a patient with SSME before ASCT 6 months after ASCT one year after ASCT value = mean of 5 serum samples +/− SD VEGF (pg/ml) 227,87 (+/−33,3) 110,81 (+/−24,8) 189,61 (+/−13,5) b-FGF (ng/ml) 17,77 (+/−0,32) 1,93 (+/−0,29) 1,64 (+/−0,37) TGF-b1 (ng/ml) 37,94 (+/−1,21) 20,45 (+/−0,85) 18,95 (+/−0,49) IL-6 (pg/ml) 92,82 (+/−3,2) 33,2 (+/−5,3) 32,0 (+/−4,5) One year after administration of high-dose melphalan and autologous hematopoietic stem cell transplantation (ASCT), the serum levels of FGF-b, TGF-b1 and IL-6 remain low. Remarkably, since the dose of thalidomide has been tapered because of persistent ulnar neuropathy, the serum concentration of VEGF is increasing but not reaching the pre-transplant levels. We conclude from this report that serum levels of VEGF, FGF-b, TGF-b and IL-6 follow the clinical evolution in this patient with SSME, suggesting a role for these cytokines in the pathogenesis of SSME.

scholarly journals 2694. Incidence of Pneumocytis jiroveci (PJP) Infection with 3-Month Prophylaxis of Aerosolized Pentamidine (AP) in Autologous Hematopoietic Stem Cell Transplantation (HSCT)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S947-S947
Author(s):  
Sarah Perreault ◽  
Dayna McManus ◽  
Rebecca Pulk ◽  
Jeffrey E Topal ◽  
Francine Foss ◽  
...  
Keyword(s):  
Cost Savings ◽  
Cost Comparison ◽  
High Dose ◽  
Potential Cost ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
One Year ◽  
Relapsed Disease ◽  
The Cost ◽  
Autologous Hsct

Abstract Background HSCT patients are at an increased risk of developing PJP after transplant due to treatment induced immunosuppression. Given the risk of cytopenias with co-trimoxazole, AP is utilized as an alternative for PJP prophylaxis. A prior study revealed a 0% (0/19 patients) incidence when AP prophylaxis was given for one year post autologous HSCT. Current guidelines recommend a duration of 3 – 6 months for PJP prophylaxis in autologous HSCT. The primary endpoint of this study was to assess the incidence of PJP infection within one year post autologous HSCT in patients who received 3 months of AP. Secondary endpoint was a cost comparison of 3 months compared with 6 months of AP. Methods A single-center, retrospective study of adult autologous HSCT patients at Yale New Haven Hospital between February 2013 and December 2017 was performed. Patients were excluded if: <18 years of age, received < or >3 months of AP, changed to alternative PJP prophylactic agent or received no PJP prophylaxis, received tandem HSCT, deceased prior to one year post-transplant from a non PJP-related infection, HIV positive, or lost to follow-up. Pentamidine was given as a 300 mg inhalation monthly for 3 months starting Day +15 after autologous HSCT. Results A total of 288 patients were analyzed, no PJP infections occurred within one year post HSCT. Additionally, 187 (65%) patients received treatment post HSCT with 135/215 (63%) receiving maintenance immunomodulatory drugs for myeloma and 40/288 (14%) patients developing relapsed disease. 43% of the chemotherapy regimens for relapsed disease included high dose corticosteroids. The cost difference of using 3 months vs. 6 months of AP is $790, reflecting the cost of drug and its administration. Applying our incidence of 0%, potential cost savings of 3 months vs. 6 months of AP would be $330,000 over 5 years or $66,000 per year. Conclusion Three months of AP for PJP prophylaxis in autologous HSCT patients is safe and effective as well as cost-effective compared with a 6 month regimen. Disclosures All authors: No reported disclosures.

Graft-versus-host disease and donor-directed hemagglutinin titers after ABO-mismatched related and unrelated marrow allografts: evidence for a graft-versus-plasma cell effect

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 1150-1156 ◽  
Author(s):  
Marco Mielcarek ◽  
Wendy Leisenring ◽  
Beverly Torok-Storb ◽  
Rainer Storb
Keyword(s):  
Plasma Cell ◽  
Graft Versus Host Disease ◽  
Plasma Cells ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Abo Incompatibility ◽  
Transfusion Requirements ◽  
Gradual Disappearance

Abstract The gradual disappearance of host antidonor isohemagglutinins after major ABO-mismatched hematopoietic stem cell (HSC) allografts has been attributed to the gradual destruction of host plasma cells by graft-versus-host effects. To corroborate this hypothesis, we retrospectively analyzed results from 383 major or major/minor ABO-mismatched unrelated and related HSC allografts performed between 1983 and 1998. All patients were conditioned by high-dose pretransplant therapy and given methotrexate/cyclosporine for graft-versus-host disease (GvHD) prophylaxis. Of the 383 patients, 155 had HLA-matched related and 228 had unrelated grafts. We asked whether unrelated recipients experienced a more rapid disappearance of isohemagglutinins than related recipients, and whether, within the groups of related and unrelated recipients, the titer disappeared faster in patients with GvHD than in those without GvHD. The median time to reach undetectable antidonor IgG and IgM titers was significantly shorter in unrelated recipients (46 versus 61 days; P = .016). In addition, related recipients with GvHD had a 2.2-fold increased likelihood (1.12-4.39,95% CI; P = .02) of reaching undetectable titers within 100 days than patients without GvHD. The persistence of antidonor isohemagglutinins led to significantly increased red blood cell (RBC) transfusion requirements in the ABO-mismatched related patients compared with ABO-matched counterparts. However, time to neutrophil and platelet engraftment, incidence of GvHD, and survival were not influenced by ABO incompatibility. In conclusion, our results corroborate the hypothesis that the rate of disappearance of antidonor isohemagglutinins after ABO-mismatched allogeneic HSC grafts is influenced by the degree of genetic disparity between donor and recipient, suggesting a graft-versus-plasma cell effect.

ACCELERATION OF BONE-MARROW RECOVERY BY PRE-TREATMENT WITH CYCLOPHOSPHAMIDE IN PATIENTS RECEIVING HIGH-DOSE MELPHALAN

The Lancet ◽  
1978 ◽  
Vol 312 (8097) ◽  
pp. 966-968 ◽  
Author(s):  
D.W Hedley ◽  
J.L Millar ◽  
T.J Mcelwain ◽  
M.Y Gordon
Keyword(s):  
Bone Marrow ◽  
High Dose ◽  
Pre Treatment ◽  
High Dose Melphalan

Comparison of conditioning regimen toxicities among autologous stem cell transplantation eligible multiple myeloma patients: High-dose melphalan versus high-dose melphalan and bortezomib

2017 ◽  
Vol 24 (4) ◽  
pp. 281-289 ◽  
Author(s):  
Eda Aypar ◽  
Fikret Vehbi İzzettin ◽  
Şahika Zeynep Akı ◽  
Mesut Sancar ◽  
Zeynep Arzu Yeğin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conditioning Regimen ◽  
Standard Of Care ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Duration Of Hospitalization ◽  
High Dose Melphalan

Background Autologous hematopoietic stem cell transplantation (AHSCT) remains the standard of care for younger patients with multiple myeloma (MM). Currently, high-dose melphalan (HDM) is recommended as conditioning regimen before AHSCT. Preclinical data suggest that combining bortezomib and melphalan has synergistic effect against multiple myeloma cells. Bortezomib and HDM (Bor-HDM) combination as conditioning regimen has been investigated by many other investigators. Objective In this retrospective study, we aimed to compare transplant-related toxicities and hematologic recovery of HDM and Bor-HDM conditioning regimens. Method We retrospectively evaluated hematologic recovery and toxicity profile in patients with MM who received AHSCT with either HDM ( n = 114) or Bor-HDM ( n = 53) conditioning regimen. Results Nonhematologic toxicities were comparable between HDM and Bor-HDM conditioning regimen, except mucositis and diarrhea being more frequent in the Bor-HDM group. Neutrophil and platelet engraftment time and duration of hospital stay were significantly shorter for HDM regimen. Conclusions In this retrospective analysis, we observed engraftment kinetics and duration of hospitalization were significantly worse in Bor-HDM conditioning regimen with manageable toxicities. Randomized studies are needed to further compare Bor- HDM regimen to HDM in terms of response rates, toxicities, and transplant-related mortality.

Outcome of IgD Myeloma After Autologous Hematopoietic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4354-4354
Author(s):  
Sofia Qureshi ◽  
Manish Sharma ◽  
Chitra Hosing ◽  
Floralyn L Mendoza ◽  
Jatin Shah ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Renal Insufficiency ◽  
Stem Cell Transplantation ◽  
Median Time ◽  
Partial Remission ◽  
Progressive Disease ◽  
High Dose ◽  
Hematopoietic Stem ◽  
High Dose Melphalan

Abstract Abstract 4354 BACKGROUND Multiple Myeloma (MM) is a clonal disorder of plasma cells characterized by monoclonal immunoglobulin (Ig) secretion. Immunoglobulin D (IgD) MM constitutes <2% of all myeloma cases and is characterized by a younger age, male predominance, frequent extra osseous disease, amyloidosis, renal insufficiency and a poor prognosis. We retrospectively analyzed the outcome of patients with IgD myeloma transplanted at our institution. METHODS Between August 1988 and June 2008, 15 patients with IgD MM (13 males, 2 females) received autologous hematopoietic stem cell transplantation (auto HCT) at MD Anderson Cancer Center. Twelve patients received high-dose melphalan (200 mg/m2) as preparative regimen; 3 patients received high-dose melphalan in combination with other agents. RESULTS At diagnosis 7/15 (47%) patients had Durie-Salmon stage III disease, 6/15 (40%) had serum creatinine ≥2 mg/dl and 6/15 (40%) had hypercalcemia. Median age at the time of auto HCT was 53 yrs (range 38–64 yrs) and median interval between diagnosis and auto HCT was 12.6 months (range 3-75 months). Prior to auto HCT 11 patients achieved a partial remission (PR), one had a very good partial remission (VGPR), 2 had minimal response (MR) and one patient had no response to induction. Median follow-up in surviving patients was 25 months. Median time to neutrophil engraftment (ANC > 500/dl) was 10 days (range 9–15 days) and for platelet engraftment (>20,000/dl) was 11 days (range 8–16 days). Non-relapse mortality at 100 days was 0%. Complete responses were seen in 6/15 (40%) patients; 3 converted from PR to CR, 2 from MR to CR and one from VGPR to CR. Only one patient progressed within 3 months of auto HCT. Kaplan-Meiers estimates of 3-year progression-free survival (PFS) and overall survival (OS) were 38% and 64%, respectively. Median time to progression was 18 months. One patient with complex cytogenetics including deletion 13q had disease progression 7 months following an auto HCT. He subsequently received an allogeneic transplant, achieved stable disease status and died 11 months later due to progressive disease. Another patient received a second auto HCT for relapse, but died 3 months later due to progressive disease. CONCLUSIONS Patients with IgD MM, despite a higher incidence of renal insufficiency and hypercalcemia at diagnosis, can safely receive auto HCT, with overall response rates, PFS and OS comparable to other MM subtypes. Disclosures: Shah: Celgene, Amgen, Novartis, Elan: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Sign in / Sign up

Export Citation Format

Share Document