scholarly journals Successful Early Outcome with Low-Dose (400 cGY) Total Body Irradiation in Combination with Busulfan and Fludarabine Myeloablative Conditioning Followed By Matched Unrelated Donor Allogeneic Peripheral Blood Stem Cell Transplantation in a Patient with Non-Remission Acute Myelogeneous Leukemia with Diffuse Extramedullary Disease in Multiple Sites

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5769-5769
Author(s):  
Gorgun Akpek ◽  
Sunita Nathan ◽  
John J. Maciejewski ◽  
Deborah A. Katz ◽  
Ashley Echeverria ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Low Dose ◽  
Mediastinal Mass ◽  
High Dose ◽  
Unrelated Donor ◽  
Post Transplant ◽  
Acute Myelogeneous Leukemia

Abstract Outcome after allogeneic stem cell transplantation (allo-SCT) is poor with 10-20% probability of long term survival in patients with acute myelogeneous leukemia (AML) not in remission at the time of transplant. The main cause of transplant failure in this high risk population is disease post-transplant relapse. We treated a 32 year-old male with undifferentiated AML (M0) who initially presented with leukocytosis, circulating blasts and a large anterior mediastinal mass abutting adjacent structures. A core biopsy of the mass revealed myeloid sarcoma. Patient developed respiratory distress requiring endotracheal intubation and mechanical ventilation. Cytogenetics revealed Hyperdiploid, 55, XY,+4,+6,+8,+9,+10,+11,+14,+19,+mar[12]/46,XY[14]. FLT3 ITD was positive. He did not respond to initial induction chemotherapy with 7+3 (daunorubicin 60 mg/m2/d and Cytarabine 100 mg/m2/d). He achieved morphologic and cytogenetic complete remission after re-induction with high dose cytarabine and mitoxantrone. He also received scheduled prophylactic triple intrathecal chemotherapies throughout his treatment course and started high dose cytarabine consolidation (HIDAC). His treatment courses were complicated by numerous medical problems, requiring a second prolonged hospitalization following third consolidation. He was intubated again due to diffuse alveolar hemorrhage. The patient was eventually discharged with tracheostomy collar and supplement oxygen, which was discontinued later on. A follow-up CT of chest showed increase in size of mediastinal mass but continuous CR in BM exam. While unrelated donor allogeneic SCT is in process, he received one course of decitabine. At the time of pre-transplant work-up, he relapsed of her AML first at his left conjunctivae and shortly after on his skin, presented with diffuse chloroma lesions on his trunk. He was treated with external radiation to his left eye with additional IT chemo (negative cytology). He underwent 10/10 HLA match unrelated donor allogeneic stem cell transplantation following PK-directed IV Busulfan with targeted AUC of 20,000 and Fludarabine 160 mg/m2 plus total body irradiation 200 cGY/d x 2 days. Skin lesions were active but bone marrow was in remission at the time of transplant. GVHD prophylaxis was tacrolimus and low dose methotrexate 5 mg/m2/d on days+1, +3, and +6 only. No ATG was given. His post-transplant course was relatively unremarkable. No major complications requiring re-admission to hospital occurred. His trach collar was kept thoughout his transplant and post-transplant courses due to tracheal stenosis. He achieved complete morphologic and cytogenetic remission with resolution all of his extramedullary leukemia including his mediastinal mass on day+100 evaluation. Currently he has been receving monthly 5-Azacitidine maintenance and clinically well on day+122. This case illustrates a successful early outcome after peripheral blood allogeneic stem cell transplantation using the combination of chemo-low dose radiation in a patient with non-remission AML with diffuse extra medullary disease. Optimum combination of radiation and chemotherapy in conditioning regimens may improve transplant outcomes in patients with non-remission AML and warrants prospective Phase I-II clinical trials. Disclosures No relevant conflicts of interest to declare.

Low-Dose Azacitidine for Relapse of MDS/AML after Unrelated Donor Peripheral Blood Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5034-5034 ◽  
Author(s):  
James M. Rossetti ◽  
Richard K. Shadduck ◽  
Chandana Thatikonda ◽  
Entezam Sahovic ◽  
John Lister
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Low Dose ◽  
Peripheral Blood Stem Cell ◽  
Unrelated Donor ◽  
Post Transplant ◽  
Blood Stem Cell Transplantation

Abstract Background: Post-transplant relapse in patients with myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) is difficult to manage. Cytogenetic relapse and decreasing donor chimerism often precedes morphological relapse. Weaning of immunosuppressive agents and donor lymphocyte infusion (DLI) may induce graft versus tumor effect (GVT), but is of limited value for patients with existing GVHD. In addition, the degree of GVT in high-risk myeloid disease is suboptimal. We present our experience using low-dose azacitidine (AZA) for cytogenetic relapse post-transplantation. Methods: Six patients with high-risk myeloid malignancy with cytogenetic relapse after matched unrelated donor peripheral blood stem cell transplantation were treated with low-dose AZA at 25 mg/m2 SC or IV for 5 days. An average of 2 cycles of AZA were given (range = 1 to 3). There were 3 females and 3 males with a mean age of 48 years (range = 31 to 59 years). Four had high-grade MDS (including 2 with treatment related disease) and 2 had high-risk AML. Conditioning consisted of fludarabine and ablative doses of busulfan in all patients. Cytogenetic relapse was seen by FISH testing within 187 days post-transplant (range = 30 to 730 days). AZA was given after an initial attempt to wean immunosuppression, which was not possible in 3 patients due to existing GVHD. All patients tolerated AZA well, without major toxicity. DLI was possible in 3 patients following AZA. A reduction in cytogenetic abnormalities (by FISH) and increase in donor chimerism (by FISH or STR) was observed in 5 out of 6 patients (83%) within 21 days post-AZA (range = 7 to 71 days). Three of the 5 responders demonstrated improvement after 1 cycle. The other 2 responders improved after 2 cycles given 28 and 60 days apart, respectively. One of these patients responded to a second AZA cycle after failing DLI. AZA did not appear to induce or worsen GVHD in any patient. One patient remains in CR 4 months after 1 cycle of AZA. Another patient demonstrated ongoing improvement in chimerism until her death from previously existing GVHD 20 days after a third cycle of AZA. The remaining 3 responders relapsed within 30 days from time of first response (range = 17 to 43 days). Conclusions: Low-dose AZA appears to have activity in post-transplant relapse of MDS and AML. This low-dose regimen appears to be well tolerated, however, response to AZA is short-lived in the majority of patients. Further investigation is planned to improve the durability of response by giving AZA at regular intervals from the time of early relapse. The utility of AZA as a preparatory regimen pre-DLI should also be explored.

Low Dose Alemtuzumab (Campath 1H) Prior to Allogeneic Stem Cell Transplantation Is Associated with Low Incidence of Acute and Chronic GVHD but Protracted Immune Recovery.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5376-5376
Author(s):  
Marcel P. Devetten ◽  
Fausto Loberiza ◽  
Robin Weisenborn ◽  
Pam Bunner ◽  
Jamie Brewer ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Low Dose ◽  
Chronic Gvhd ◽  
High Dose ◽  
Low Incidence ◽  
Cmv Reactivation

Abstract Background: The administration of alemtuzumab (Campath 1H) as part of the conditioning regimen prior to allogeneic stem cell transplantation has been associated with a low incidence of acute and chronic GVHD. Initial studies employing doses of 100 mg have reported a high incidence of viral infections. Lower alemtuzumab doses combined with standard GVHD prophylaxis regimens (calcineurin inhibitor + MTX) have also resulted in a low incidence of acute GVHD in patients with CD52-positive malignancies. We investigated the effect of low-dose (40 mg) alemtuzumab on engraftment (VNTR chimerism studies), the incidence of acute and chronic GVHD, CMV reactivation, survival, and immune reconstitution (examined by TREC content at various time points after transplant). Patient and Transplant characteristics: Twenty-seven patients underwent a matched (n=24) or 1-antigen mismatched (n=3) related (n=13) or unrelated (n=14) allogeneic stem cell transplantation for various hematologic malignancies. Median age was 41 years (19–59). Disease stage at transplant was early for 48%, intermediate for 11% and late for 41%. Three patients received bone marrow and 24 received PBSC grafts. Conditioning regimen consisted of TBI 10 Gy with partial lung shielding, Thiotepa 500 mg/m2, and Alemtuzumab 20 mg IV on day -4 and day -1. GVHD prophylaxis was with cyclosporine (n=13) or tacrolimus (n=14) and full-dose MTX. High-dose viral prophylaxis with valacyclovir 2000 mg QID was given to all recipients from a CMV seropositive recipient/donor pair starting at patient #9, due to a high incidence of CMV reactivation amongst the first 8 patients. Three patients received DLI for disease relapse. Median follow-up for survivors is 13 months (6–26). Results: Of eighteen evaluable patients (3 relapsed, 5 expired, 1 not done) at day 100, 15 had ≥ 95% donor chimerism, and 3 had 90–94% donor chimerism. The cumulative incidence of acute GVHD grade II-IV at day 100 was 4% (95% CI 1–16%), and the cumulative incidence of chronic GVHD at 1 year was 31% (12–52%). Cumulative incidence of non-relapse mortality at day 100 was 18% (7–35%), and at 1 year 31% (14–49%). Cumulative incidence of relapse at 1 year was 28%, resulting in a projected 1-year disease-free survival of 41% (22–60%), and overall survival of 54% (33–71%). Amongst the first eight patients, all (5/5) at-risk recipients developed CMV reactivation. After initiation of prophylaxis with high-dose valacyclovir, 4/11 at-risk recipients developed CMV reactivation. No patient died from CMV disease. TREC analysis in a limited number of patients showed rapid increase in TREC between day 0 and day 180, but no further increment between day 180 and day 365. Conclusions: The use of low-dose alemtuzumab results in low incidences of acute and chronic GVHD. CMV reactivation is common, and can be partially prevented by use of high-dose valacyclovir. Immune reconstitution data on a small subset of patients show limited output of thymic emigrant T cells after 6 months.

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