ALBERT

Description: Immune mediated demyelinating disease after allogeneic stem cell transplantation is a rare entity with unclear etiology. Acute inflammatory demyelinating polyneuropathy (AIDP) has been reported post related and unrelated allogeneic stem cell transplantation but no such case has been reported post unrelated cord blood transplantation. We hereby present the first case of GBS post double umbilical cord blood transplantation (DUCBT). A 55 year old male with relapsed refractory CLL received DUCBT with two 5/6 matched cord units (antigen level HLA-A, HLA-B and allele level HLA-DRB1) with fludarabine, cytoxan and total body irradiation based reduced intensity conditioning regimen. Graft versus host disease (GVHD) prophylaxis was with cyclosporine and mycophenolate. Early post transplant course was complicated by grade 4 acute GVHD of the gut with a complete resolution with steroid therapy and successful taper of all immunosuppression by day 180. 7 months post transplantation, patient presented with skin rash and tingling in both feet that progressed rapidly to lower extremity paralysis over the course of 2 days. Physical exam showed macula-papular rash affecting his upper extremities, upper chest and back area. Neurologic exam was significant for motor weakness in lower extremities 2/5, plantar flexion and knee flexion 3/5. He had loss of deep tendon reflexes in both lower extremities (Achilles and Patellar) and upper extremities (biceps and triceps).Workup revealed normal blood counts, organ function, vitamin B12, folate, TSH level, free cortisol. Serum electrophoresis and immunfixation was also normal. Magnetic resonance imaging of the central nervous system showed mild neural foramina narrowing at the L4-L5 level. Serology for Lyme disease, Epstein Bar virus (EBV), syphilis, cytomegalo virus (CMV), Hepatitis, HIV, toxoplasma, enterovirus and human herpes virus 6 was negative. Blood tests for autoimmune markers including (anti-nuclear antibody)ANA, acetylcholine esterase and volted calcium channel antibodies were normal. A lumbar puncture was performed and showed a high protein level of 67mg/dl, 1 nucleated cell/mm3 and normal glucose level. Cerebrospinal fluid was negative for oligoclonal bands, West Nile virus, cryptosporidium, HHV6, herpes virus 1 and 2, gram stain and cultures. Nerve conduction studies and needle electormyegraphy was suggestive of acute demyelinating polyneuropathy. Based on the above workup, he was diagnosed with GBS and started on therapy with intravenous immunoglobulin at 0.5gm/kg for 4 days and prednisone 1mg/kg daily for the treatment of GVHD. Etiology of GBS was presumed to be related to GVHD as his workup was negative for campylobacter, HIV and CMV. He improved significantly over the next 4 weeks and became ambulatory without assistance but his weakness symptoms relapsed as his prednisone was tapered. Prednisone was increased again to 1mg/kg and sirolimus was started. Patient was successfully tapered of prednisone and remains fully ambulatory without assistance or evidence of GVHD on single agent sirolimus 13 months post DUCBT. This is the first case of autoimmune demyelinating polyneuropathy post DUCBT with association of GVHD that was managed successfully with a combination of intravenous immunoglobulins, steroids and sirolimus. Disclosures: No relevant conflicts of interest to declare.

Description: Acute myeloid leukemia (AML) continues to be one of the most common myeloid malignancies in the United States. Achieving a complete response (CR) after induction with standard daunorubicin and cytarabine (7+3) remains suboptimal, occurring in 55-65% of patients. No significant advances have improved these outcomes in the last decade. A recent phase III randomized clinical trial by the Polish Adult Leukemia Group (PALG), showed that adding cladribine 5mg/m2 to standard 7+3 (Daunorubicin 60mg/m2, Ara-C 200mg/m2) improved CR rates to 68% vs 56% with standard 7+3 alone. Achieving a higher CR is important in the outcome of high-risk patients who require allogeneic stem cell transplantation (Allo-SCT) as a curative measure. At our center, we conducted a retrospective analysis evaluating the addition of cladribine to the current standard of care treatment in newly diagnosed AML. We hypothesized an improvement in CR rates in all-risk patients will allow more patients to proceed to Allo-SCT. Adult patients 18 years of age or older with newly diagnosed AML who received remission induction chemotherapy between May 2012 and May 2018 were included in the study. A total of 118 AML patients were screened and those who did not complete induction or did not have bone marrow biopsy at end of induction chemotherapy were excluded. A total of 100 patients were evaluable of which 26 (26%) received DAC and 74 (74%) received 7+3. Within the 7+3 group, 29 (39%) received a Daunorubicin dose of 60mg/m2 (D60) and 45 (61%) received a dose of 90mg/m2 (D90). A higher absolute CR rate was noted after one induction in the DAC group as compared to the combined 7+3 group (21 [80.7%] vs. 49 [66.2%], respectively). The improvement in CR between DAC and D60 reached statistical significance (p=0.043) but there was no statistically significance difference in CR rates between DAC vs D90 (p=0.48). It is interesting to note that more patients in D60 (39%) and D90 (26%) group required re-induction as compared with DAC (12%) (p=0.067). Median overall survival (OS) for the DAC group was not reached, while median OS for D60 was 10 (DAC vs D60 p=0.076) and for D90 was 28 months (DAC vs D90 p=0.97). In the subgroup of patients who underwent Allo-SCT, median OS in the D90 group was 30 months (DAC vs D90 p=0.43) while not reached in the DAC and D60 group (DAC vs D60 p=0.84). For all patients, the median relapse-free survival (RFS) for the DAC cohort was not reached. Median RFS was 12 months for D60 (DAC vs D60 p=0.047) and 25 months for D90 (DAC vs D90 p=0.166) groups. There was no difference in OS and RFS between all three groups who were transplanted in first CR (CR1). In conclusion CR rates following induction chemotherapy were higher in DAC vs Daunorubicin groups, however only statistically significant with respect to D60. Additionally a statistically significant improvement in RFS and a trend towards improved OS was noted in favour of DAC vs D60. Regardless of the induction chemotherapy, there was no difference in OS and RFS of patients who were transplanted in CR1. These results have encouraged us to perform a prospective comparison of standard 7+3 with Dauno 90mg/m2 and DAC. Disclosures No relevant conflicts of interest to declare.

Description: Introduction Plerixafor is a reversible CXCR4 antagonist that has been approved by the food and drug administration for autologous hematopoietic stem cell mobilization in patients with multiple myeloma and non-Hodgkin’s lymphoma. Patients mobilized with Plerixafor were shown to have a higher proportion of primitive stem cells (CD34+/CD133+/CD38-), CD4+ T cells and Natural killer cells (CD3-/CD16+/CD56+) in the graft composition when compared to patients mobilized with chemotherapy plus G-CSF alone .We investigated the effect of Plerixafor on immune reconstitution at thirty and sixty days post autologous stem cell transplantation. Methods Patients eligible for autologous stem cell transplantation were enrolled on a single arm prospective immune reconstitution trial. A complete blood count, differential and lymphocyte flow cytometry panel (T cell, NK cell and B cell markers) was checked on Days 30 and 60 post autologous transplantation. Stem cell mobilization was carried per our institutional standards. All patients received subcutaneous G-CSF at a dose of 10 µg per kilogram body weight for four consecutive days. On Day4, patient with a peripheral CD34 count of ≤20/µl received plerixafor 0.24mg/kg. Collection was started on day 5 and continued till collection goal was reached or patient failed to get the minimal cell dose after 4 consecutive days of aphaeresis. Results 49 patients were enrolled during the period from September 2010 till May 2012. Median age at time of transplantation was 54 years (range 21; 72 years). 35 patients had multiple myeloma and 14 had non-Hodgkin’s lymphoma. 16 patients received GCSF alone (group A) and 33 had plerixafor plus GCSF (group B) for mobilization. All patients achieved the minimum target of CD34 collection. The mean number of collection days was 1.9 and 1.4 days (p=0.05) with a total collection dose of 7.76 and 7.61 CD34 x106/Kg for groups A and B respectively. The percentage proportion of CD34 in the aphaeresis product was 0.73% and 0.75% (p=0.9) for group A and B. Total infused CD34 dose was similar in both groups (4.88 and 4.56 CD34x106/kg) with time to engraftment of 11.68 vs 11.69 days for neutrophils and 20.62 vs 21.39 for platelets in groups A and B respectively. There was no difference between day 30 absolute lymphocyte count (1.09 vs 1.44 x103/mm3 p=0.18); Absolute NK cell (0.31 vs 0.35 x103/µl; p=0.51); absolute T cell count (0.71 vs 0.96 x103/µl p=0.33) and absolute neutrophil count (2.98 vs 2.63 x103/mm3 p=0.37). The cell count recovery was also not significantly different when analyzed per disease (myeloma or non-Hodgkin’s lymphoma) and at day 60. Conclusion Our study shows that patient mobilized with plerixafor and G-CSF have similar immune reconstitution at 30 and 60 days post autologous transplantation compared to patients mobilized with G-CSF alone. Disclosures: No relevant conflicts of interest to declare.

Description: Low Dose Thymoglobulin Result in Improved Outcomes after Allogeneic Unrelated Hematopoietic Stem Cell Transplantation (HCT) for Patients with Acute Myeloid Leukemia/ Myelodysplastic Syndrome Conditioned with Intravenous Busulfan and Fludarabine. Intravenous Busulfan/Fludarabine (Bu/Flu) based conditioning regimens have resulted in lower treatment related mortality (TRM) after allogeneic HCT in both reduced and full intensity dosing in AML/MDS. The addition of thymoglobulin to such regimens to minimize the risk of graft versus host disease after unrelated donor (MUD) HCT has been linked to the increased concerns of relapse risk. Method In order to study the impact of addition of low dose thymoglobulin to Bu/Flu regimens in MUD recipients, the medical records of 38 consecutive AML/MDS patients who underwent MUD HCT with BU/Flu and low dose thymoglobulin were retrospectively reviewed. All the patients received single daily dose of iv Bu 3.2 mg/kg for 2 days (RIC, Bu2-Flu) or 4 days (FIC, Bu4-Flu) based on age,  older or younger than 65 respectively. Fludarabine was given as a single daily dose of 40 mg/Kg for 4 days. Graft versus host disease prophylaxis was Tacrolimus/Methotrexate in FIC recipients and Tacrolimus/Mycophenolate in RIC recipients. Additionally, all the patients received thymoglobulin 1.5 mg/Kg on day -3, -2 and -1. All patients received peripheral stem cells except one patient with mismatch MD who received bone marrow product. Results Patient Characteristics are shown in Table 1. All the patient engrafted except one who received marrow product.  All the patients but 3 (8%) achieved 90% or more donor chimerism by day 100. With Mean follow up of 500 days (range, 100-1242) the overall survival (OS) was 77% ± 7 (CI 63-91%) at 1 year and 67% ± 9 (CI 49-85%) at 2 years. Similarly, disease free survival was 66% ±8 (CI 50-82%) at 1 and 2 years. Cumulative incidence of acute GVHD grade II-IV was 55% with grade III-IV 12%. Cumulative incidence of chronic GVHD at 1 year was 43% with extensive chronic GVHD in 17%. The regimen was associated with low treatment related mortality (TRM) with cumulative incidence of only 5% at one year, CI 14-21%. The cumulative incidence of relapse at one year was 29%, CI 17-49%. On univariate analysis only high risk CIBMTR status was predictive of poor OS (p=0.05). Conclusion The addition of low dose thymoglobulin to RIC and FIC regimens with iv Busulfan/Fludarabine prior to MUD HCT results in low TRM and improved OS for patients with AML/MDS. Relapse rate does not seem to be increased in this cohort by the addition of low dose thymoglobulin in comparison to historical control. Disclosures: No relevant conflicts of interest to declare.