scholarly journals Successful Management of Progressive Multifocal Leukoencephalopathy Post TCR Alphabeta/CD19 Depleted Haploidentical Stem Cell Transplant

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5699-5699 ◽  
Author(s):  
Satya Prakash Yadav ◽  
Shruti Kohli ◽  
Sagar Nivargi ◽  
Dhwanee Thakkar ◽  
Neha Rastogi
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Jc Virus ◽  
Neurological Deficits ◽  
Cell Transplant ◽  
Successful Management ◽  
Peripheral Blood Stem Cells ◽  
Blood Stem Cells ◽  
Alpha Beta

Abstract Introduction- Progressive multifocal leukoencephalopathy (PML) caused by JC virus is a rare but mostly fatal viral disease of brain affecting immunosuppressed patients. Here we describe successful management of JC virus induced PML in a young man post TCR alphabeta/CD19 depleted haploidentical hematopetic stem cell transplant (HSCT). Methods-A 22-year old, male with thalassemia major underwent TCR alpha-beta/CD19 depleted haploidentical HSCT in March 2014 from his 5/10 matched brother as donor. Intensive chelation and hydroxyurea were administered for 6-months before HSCT. The conditioning was with thiotepa 10 mg/kg, fludarabine 150 mg/m2, cyclophosphamide 29 mg/kg and Rabbit ATG (thymoglobulin) 4.5 mg/kg. Peripheral blood stem cells (16 million/kg CD34+ cells) were harvested and infused after TCR alpha-beta/CD19 depletion. He had primary graft rejection but had autologous recovery by day+40. He underwent a second TCR alphabeta/CD19 depleted haploidentical HSCT 6-months later from his father as donor (5/10 matched). He underwent splenectomy 3-months prior to 2nd HSCT. As anti-HLA antibodies were present so he was treated with rituximab, plasmapheresis and bortezomib over 4 weeks which was followed by conditioning with alemtuzumab-1mg/kg, fludarabine 150mg/m2, treosulfan 42g/m2 and thiotepa 8 mg/kg. Peripheral blood stem cells (9 million/kg) were infused after TCR alphabeta/CD19 depletion. Neutrophils engrafted on day+11 and platelets on day+13.He developed grade I skin graft vs. host disease (GVHD) which was treated with sirolimus. It was changed to tacrolimus on day+180 for chronic skin GVHD and dryness of eyes.Chimerism on day+30, 100 and 1-year was fully donor. At 1-year his lymphocyte counts showed CD4-157/ul, CD8-368/ul, CD19-1055/ul and CD16/56-600/ul. Results- One-year post HSCT, he was re-admitted with right sided complex partial seizure. He was on tacrolimus, amlodipine and co-trimoxazole. He had severe headache. He was fully conscious, oriented and had no neurological deficits. Over next few days he developed aggressive behavior, hallucinations and short term memory loss. CT head showed left parieto-occipetal region edema. MRI brain with contrast and spectroscopy showed non-contrast enhancing white matter changes in the region corresponding to CT scan. CSF showed no cells and protein & sugar were normal. However CSF was positive by PCR for JC virus confirming the diagnosis of PML.Quantitative PCR in CSF showed 21000 copies/ml of JC virus. Tacrolimus was stopped. He was then started on intravenous cidofovir with oral probenicid as per protocol. Cidofovir 5mg/kg loading dose followed by 3 mg/kg once a week for 8 weeks. JC virus copies reduced to 1200/ml in CSF after 3 weeks and became negative after 5 weeks. Tablet risperidone (2 mg orally twice daily) was given to block serotonin receptor mediated uptake of virus in oligodendrocytes for 2 months. Tablet mefloquine was also given for its antiviral effect in JC virus-5mg/kg daily for 3 days followed by once weekly for 6 months. His condition improved and was discharged a month later. He is very well now more than 3-years after JC virus infection.He has no neurological deficits and memory is normal. He is off all medications and has no GVHD. Conclusion - JC virus induced PML post HSCT can possibly be managed by removing immune suppression adding risperidone and giving antiviral cidofovir and mefloquine. Disclosures No relevant conflicts of interest to declare.

Seizures During Infusion of Autologous Peripheral Blood Stem Cells Are Related to High White Blood Cell Concentration in the Peripheral Blood Stem Cell Product and Can Be Prevented by Dilution of Product with Autologous Plasma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4386-4386
Author(s):  
Carlos Bachier ◽  
Grant Potter ◽  
Joshua Potter ◽  
Charles F. LeMaistre ◽  
Paul Shaughnessy ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Blood Cell ◽  
White Blood Cell ◽  
Peripheral Blood ◽  
Cell Transplant ◽  
Autologous Plasma ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract Abstract 4386 Seizures are rare during infusion of autologous peripheral blood stem cells (PBSC). We retrospectively analyzed 159 adult patients (pts.) collected consecutively between January 2006 and July 2009. Pts. were collected on either COBE Spectra (COBE) (n=85) or Fresenius AS 104 (Fresenius) (n=74) cell separators and mobilized with granulocyte colony stimulating factor (G-CSF) alone (n=47), G-CSF and Plerixafor (n=26), or G-CSF and chemotherapy (n=66). Pts. characteristics did not differ between the COBE and Fresenius cohorts, but there were differences in PBSC product (Table). Pts. collected with COBE had higher white blood cell (WBC) and total nucleated count (TNC) but lower mononuclear cell (MNC) percentage and cell viability than pts. collected with the Fresenius. Absolute CD34+ cells in the PBSC product, CD34+ cells / kg and total CD34+ cells / kg infused at transplant were not significantly different. CD34+ yields (calculated as the ratio of CD34+ cells /μl of the PBSC product to the patient's peripheral blood CD34+ cells / μl taken on the day of collection) were significantly higher on the COBE than Fresenius. No serious adverse events occurred during PBSC infusion except 3 of 159 pts. developed seizures during infusion of PBSC; all collected on the COBE and all three had product WBC > 590 × 103/μl (compared to a median of 163.3 × 103/ μl for all other products)(Figure). Evaluation of pts. did not identify abnormalities in imaging studies, cerebrospinal fluid analysis, electrolytes, or past history which might explain etiology of seizures. No significant difference in WBC or platelet engraftment was observed in pts. collected with COBE or Fresenius. We then prospectively correlated WBC counts midway and at the end of PBSC collections. Fourteen pts. had 15 apheresis using the Fresenius. Mid- and post-WBC concentrations were 64 +/− 23 × 103/μl and 69 +/− 20 × 103/μl, respectively. Fifty-one pts. had 66 apheresis using COBE, with WBC counts obtained midway and at the end of collection of 287 +/− 150 × 103/μl and 273 +/− 144 × 103/μl, respectively. Mid-WBC accurately correlated with WBC at the end of the collection in both the COBE and Fresenius cohorts (r2 = 0.940 and r2 = 0.904, respectively). Using this information, we prospectively evaluated 65 pts. who underwent 80 PBSC collections in anticipation of an autologous (n=44) or allogeneic (n=7) stem cell transplant between June 2009 and January 2010. Collections for these pts. were performed using the COBE (n=66) or the Fresenius (n=15). Mid-WBC were obtained and products with mid-collection WBC concentration > 450 × 103/uL (n=29) had additional autologous plasma collected at the time of collection for final product dilution to < 450 × 103/uL prior to cryopreservation. Pts weight, volume of PBSC product and CD34+ cells/kg infused did not differ between the pts who received diluted PBSC product and those who did not. There were also no differences in either ANC (12 ± 1.3 days vs. 11.5 ± 1.3 days, dilution vs. non-dilution, p = 0.760) or in platelet engraftment (18 ± 3.7 days vs. 16 ± 2.7 days, dilution vs. non-dilution, p = 0.561). No serious adverse infusion effects were observed in either group. In conclusion, high number of WBC in COBE collections is a possible cause of PBSC infusion related seizures. No seizures were observed after dilution of PBSC with high WBC concentration.TIENT AND PRODUCT CHARACTERISTICSCOBE (±SD)Fresenius (±SD)Number of Products165180Number of Patients8574Age at collection56 ± 1456 ± 15Weight at Collection (kg)82.7 ± 17.979.5 ± 15.9Collections / Patient2 ± 12 ± 1Blood Volume Processed at end of Collection (L)18.0 ± 2.418.1 ± 2.7(*)Product Volume (ml)241 ± 56.8402 ± 72.0Peripheral WBC (103/ μl)36.6 ± 18.933.3 ± 24.5(*)Product WBC(103/ μl)163.3 ± 136.055.8 ± 29.3(*)TNC (1010)3.51 ± 1.861.95 ± 1.19(*)MNC (1010)2.36 ± 1.191.60 ± 0.09(*)MNC (%)75.0 ± 23.385.0 ± 10.8Volume prior to freezing(ml)100 ± 54100 ± 32(*)Post Freeze Viability (%)70 ± 1475 ± 10Peripheral CD34+/ μl24.0 ± 43.825.3 ± 79.1(*)Product CD34+/μl726.7 ± 1325.9264.63 ± 781.0(*)Product / Peripheral CD34+24.87 ± 10.9010.91 ± 6.64Absolute Product CD34+ cells (108)1.77 ± 3.521.14 ± 3.35Product CD34+/kg (106)2.02 ± 4.671.39 ± 4.15Total CD34+ cells infused (106 / kg)3.85 ± 3.203.85 ± 2.24(*) = p values < 0.05 Disclosures: No relevant conflicts of interest to declare.

Collection of Peripheral Blood Stem Cells in Patients with Multiple Myeloma after Stem Cell Transplant: A Single Institution Experience

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5435-5435
Author(s):  
Umang Swami ◽  
Lindsay Dozeman ◽  
Annick Tricot ◽  
Kamal Kant Singh Abbi ◽  
Guido J Tricot
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Median Number ◽  
Cell Transplant ◽  
Peripheral Blood Stem Cells ◽  
Blood Stem Cells ◽  
History Of ◽  
Stem Cell Collection

Abstract Background Autologous stem cell transplant is the standard of care for eligible multiple myeloma patients. However, many patients relapse with passage of time. These patients often do not have any or have inadequate numbers of previously harvested stem cells. The question still comes up frequently whether peripheral blood stem cells can be successfully collected from patients with history of prior transplant and what is the best approach. Herein, we report the results from our institution. Patients and Methods Records of patients with multiple myeloma who received transplant at our institute between 03/01/12 -07/09/15 dates were reviewed. Recorded data included disease stage, prior transplant and chemotherapies, stem cell mobilization strategies and time to engraftment. Student T-test was performed on reviewed data. Results A total number of 21 patients (7 male and 14 female) with multiple myeloma and prior transplant underwent peripheral blood stem cell collection. Median age at diagnosis was 52.1 years (range 36-71 years). Each patient had at least 2 prior rounds of chemotherapy with a median of 4 prior lines of chemotherapies (range 2-6). One patient had a prior history of allotransplant and remainder had at least one prior autotransplant. ISS staging at diagnosis included 5 patients with Stage 1, 2 patients with Stage 2, 5 patients with Stage 3 and stage was not available for 8 patients. One patient had plasma cell leukemia. Disease subtypes included two patients with IgA kappa, one with IgA lambda, nine with IgG kappa, two with IgG lambda, five with kappa light chain, one with lambda light chain and one with non-secretory disease. 33% of patients had high risk cytogenetics at time of stem cell collection. The total number of prior transplants before stem cell collection was 25 with a median of 1 transplant (range 1-2). Median age at the time of collection was 59.3 years (range 43-81). Disease status at time of salvage transplant included complete response in 5 patients, very good partial response in 2, partial response in 9 and stable disease in 5 patients. Filgrastim with plerixafor was used for mobilization in 15 patients, filgrastim, plerixafor and pegfilgrastim in 5 patients and filgrastim with pegfilgrastim in 1 patient. A median number of 3 doses of plerixafor (range 0-5) were used. Median stem cell collection dose was 9.75 X 106/kg CD34 cells (range 3.29-24.8 X 106/kg) and median number of collection days was 3 (range 1-5). All patients received salvage transplants. Engraftment occurred at a median of 12 days (range 10-27). The 21 patients received a total number of 30 transplants after collection with a median of 1 transplant (range 1-2). Prior to collection, D-PACE was administered to 10 patients, VDT-PACE to 2 patients, VCD to 1 patient and growth factors only to 8 patients. 5/8 patients who were mobilized with only growth factors had baseline platelet count of < 130,000. Patients receiving D-PACE had a median collection of 13.55 X 106 cells as compared to 5.70 X 106 cells without it (p<0.004). Conclusions Our experience shows that collecting peripheral blood stem cells after prior transplantation in patients with multiple myeloma is very feasible even in patients with multiple lines of chemotherapies. Addition of D-PACE as chemo-mobilization strategy has proved to be effective if platelet count is normal at baseline. Disclosures No relevant conflicts of interest to declare.

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