scholarly journals The Prognostic Significance of Peripheral Blood Mixed Chimerism After T-Cell Depleted Allogeneic Stem Cell Transplant

2013 ◽  
Vol 19 (2) ◽  
pp. S301-S302
Author(s):  
Amanda L. Olson ◽  
Rachel Lehrman ◽  
Sean Devlin ◽  
Molly Maloy ◽  
Hugo Castro-Malaspina ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Peripheral Blood ◽  
Stem Cell Transplant ◽  
Prognostic Significance ◽  
Mixed Chimerism ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant

scholarly journals Striving to cure adult T-cell leukaemia/lymphoma: a role for allogeneic stem cell transplant?

2016 ◽  
Vol 51 (12) ◽  
pp. 1549-1555 ◽  
Author(s):  
E H Phillips ◽  
A Hodson ◽  
O Hermine ◽  
A Bazarbachi ◽  
K Cwynarski
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplant ◽  
Cell Leukaemia ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant

scholarly journals A Rare Case of Chronic Myelogenous Leukemia Presenting as T-Cell Lymphoblastic Crisis

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Parikshit Padhi ◽  
Margarita Topalovski ◽  
Radwa El Behery ◽  
Eduardo S. Cantu ◽  
Ramadevi Medavarapu
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Chronic Myelogenous Leukemia ◽  
Stem Cell Transplant ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Blast Crisis ◽  
Myelogenous Leukemia ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant

Chronic Myelogenous Leukemia in blast crisis can manifest as either myeloid (more common) or lymphoid blast crisis. Most lymphoblastic crises are of B-cell lineage. T-cell blast crisis is extremely rare, with only a few reported cases. We present a case of a middle-aged man who was diagnosed with CML on peripheral blood and bone marrow biopsy. Because of a generalized lymphadenopathy noted at the time of diagnosis, a lymph node biopsy was also performed, which revealed a T-cell lymphoblastic leukemia/lymphoma, BCR/ABL1 positive, with clonal evolution. This is a very rare manifestation of CML in blast crisis with no standard treatment and with poor outcomes despite chemotherapy or allogeneic stem cell transplant. Given its rarity, it would be difficult to develop standard chemotherapy protocols. We believe the treatment for this condition should be similar to any lymphoid blast crisis. The patient was treated with induction chemotherapy (hyper-CVAD regimen) plus dasatinib for 3 cycles followed by sibling-donor allogeneic stem cell transplant and is currently on maintenance dasatinib and has minimal residual disease at this time.

scholarly journals T-Cell Replete Allogeneic Stem Cell Transplant Is an Effective Treatment Option for Patients with TP53 mutated Mantle Cell Lymphoma

2021 ◽  
Vol 27 (3) ◽  
pp. S421-S422
Author(s):  
Edward Robert Scheffer Cliff ◽  
Thomas Eliot Lew ◽  
Piers Blombery ◽  
Michael Dickinson ◽  
Constantine S. Tam ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Mantle Cell Lymphoma ◽  
Effective Treatment ◽  
Stem Cell Transplant ◽  
Cell Lymphoma ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Effective Treatment Option ◽  
Mantle Cell

Clofarabine, Melphalan, and Thiotepa, Followed by Allogeneic Unmodified Bone Marrow or Peripheral Blood Stem Cell Transplant, by Unmodified Double Cord Blood Transplant, or by CD34+ T-Cell Depleted Stem Cell Transplant for the Treatment of Hematologic Malignancies.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3144-3144
Author(s):  
Farid Boulad ◽  
Guenther Koehne ◽  
Nancy A. Kernan ◽  
Susan E. Prockop ◽  
Trudy N. Small ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
T Cell ◽  
Peripheral Blood ◽  
Graft Failure ◽  
Stem Cell Transplant ◽  
Hematologic Malignancies ◽  
Cell Transplant ◽  
Acute Leukemias

Abstract Abstract 3144 Based on encouraging results with the use of clofarabine (CLO) for reinduction treatment of acute leukemias, we have developed two allograft protocols for patients with hematologic malignancies with a cytoreductive regimen, using CLO in combination with melphalan (Mel) and thiotepa (Thio). Patients on protocol #1 received unmodified bone marrow (BMT), peripheral blood stem cells (PBSCT), or unmodified double unit cord blood (dCBT). Patients on protocol #2 received CD34+ T-cell depleted stem cells (TCD-SCT). Cytoreduction consisted of CLO 20 mg/m2/day × 5, Thio 10 mg/Kg/day × 1 and Mel 70 mg/m2/day × 2. Graft-versus-host disease (GvHD) prophylaxis consisted of tacrolimus (Tacro) and methotrexate (MTX) with unmodified BMT or PBSCT, tacro and mycophenolate mofetil (MMF) with unmodified dCBT, and none with TCD-SCT. Rabbit ATG at 2.5 mg/Kg × 2 or 3 doses was used for the prevention of rejection with the TCD-SCT. To date, 64 pts were treated with this regimen including: unmodified BMT/PBSCT 27 patients, dCBT 15 patients, and TCD-SCT 22 patients. The median age for patients was 10.2 years (range 0.9–58.7) for unmodified SCT and 41.5 (range 0.6–67.2) for TCD-SCT. This was the second SCT for 13 of 27 pts in the BMT-PBSCT group, 2 of 15 pts in the CBT group, and 4 of 22 pts in the TCD group. Patient diagnoses included acute lymphoblastic leukemia (ALL) (N=36), acute myelogenous leukemia (AML) (N=23), and myelodysplastic syndrome (MDS) (N=5). Patients with ALL or AML in first remission (CR1) or CR2 and MDS in CR1 or refractory anemia (RA) were categorized as having good risk disease (GRD), while all other pts were considered to have poor risk disease (PRD), irrespective of all other factors. There were 15 of 27 pts with PRD in the BMT/PBSCT group, 10 of 15 pts in the CBT group, and 9 of 22 pts in the TCD-SCT group. For the unmodified BMT/PBSCT group, donors were HLA-matched related (N=11), mismatched related (N=1), matched unrelated (N=12), or mismatched unrelated (N=3). All CBT recipients received double-unit grafts from 2 mismatched unrelated donors. For the TCD-SCT group, donors were HLA-matched related (N=8), mismatched related (N=1), matched unrelated (N=4), or mismatched unrelated (N=9). Engraftment occurred in 59 of 61 evaluable pts; three pts died before engraftment. One pt recipient of unmodified BMT/PBSCT suffered a late graft failure, and one pt recipient of CBT suffered an early graft failure in the context of sepsis. Grade 2–4 acute GvHD occurred in 8/26 (31%) evaluable pts in the BMT/PBSCT group, 5/13 (38%) evaluable pts in the CBT group, and 4/20 (20%) evaluable pts in the TCD-SCT group. With a median follow-up of 20.5 months for the unmodified SCT groups and 15.4 months for the TCD group, the overall survival (OS) and disease-free survival (DFS) rates were: 53.7% and 41.0% for the BMT/PBSCT group, 51.3% and 41.5% for the CBT group, and 64.1% and 60.7% for the TCD-SCT group. This cytoreductive regimen represents a promising approach for the transplantation of patients with acute leukemias without the use of total body irradiation. This regimen is also sufficiently immunosuppressive to insure consistent engraftment of T-cell depleted transplants. Lastly, it appears to be relatively well tolerated for younger pts requiring a second SCT. Disclosures: Off Label Use: Clofarabine.

Engraftment Kinetics After Alimtuzumab-Based Allogeneic Stem Cell Transplant (SCT): Full Donor T-Cell Chimerism Did Not Predict for Acute Graft Versus Host Disease (GVHD) or CMV Reactivation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4162-4162
Author(s):  
Henry C. Fung ◽  
Muhammed Alikhan ◽  
Lela Buckingham ◽  
John J. Maciejewski ◽  
Reem Karmali ◽  
...  
Keyword(s):  
T Cell ◽  
Acute Gvhd ◽  
Stem Cell Transplant ◽  
Mixed Chimerism ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Graft Versus Host ◽  
Gvhd Prophylaxis ◽  
Cmv Reactivation

Abstract Abstract 4162 Background: Graft versus host disease (GVHD) remains the leading cause of the treatment failures following an otherwise successful allogeneic Stem Cell Transplant. Alemtuzumab – based prophylactic regimens is evolving as an important option for prevention of this devastating complication. Multiple phase II studies suggested that patients who received Alemtuzumab –containing GHVD prophylactic regimens tends to have less acute GVHD though the utility is limited by increased incidence of mixed chimerism often requiring donor lymphocytes infusion and cytomegalovirus reactivation. Hypothesis: We hypothesize that if we could identify an optimal dose of Alemtuzumab; we could maintain the benefit of lowering the incidence of GVHD and also minimize mixed chimerism and CMV reactivation following the transplant. Method: To test our hypothesis, we conducted a pilot study utilizing the combination of Alemtuzumab (20 Related Donor: 30 mg on Day -1; 10 Unrelated donor: 30 mg daily on Day -2 & Day -1) and cyclosporine as GVHD prophylaxis. Between 5/11 and 5/12, 28 pts were included in the study. There were 15 females and 13 males. The diagnosis included 16 AML, 3 NHL, 2 MDS, 1 CML, 1 CLL, 1 ALL, 1 HD, 1 PLL, 1 MPD and 1 MM. Conditioning regimens consisted of Fludarabine/Melphalan in 20, Fludarabine/Busulfan in 5, TBI/Cy in 2 and Fludarabine/Clofarabine in 1. Upon achievement of engraftment, we monitor CMV by PCR weekly and engraftment by Short tandem repeat (STR) monthly with T-cell and Myeloid subsets analysis. Results: 26/28 pts achieved neutrophils engraftment except 1 died shortly after SCT from heart failure and 1 experienced primary graft failure with day 30 STR showing only 3% donor T-cell chimerism. On Day 30 post-SCT, all evaluable pts had predominately donor T-cell (median 99%; 19/27 (70%) ≥ 99%; range 82 to > 99%) and Myeloid Chimerism (24/26 (92%) ≥ 99% except one pt who developed rapidly progressive leukemia phase PTLC after transplant. 25 pts (89%) survived beyond Day 90 post-SCT and have engraftment data available for analysis. On Day 90 analysis, while most pts maintain predominant donor myeloid chimerism (> 95%; median 99%); only 10/25 (40%) had maintained 99% donor T-cell chimerism. In addition, 76% pts had their T-cell donor chimerism worsened by Day 90 when compared with Day 30 analysis (9 pts dropped below 80%; range 8–75%). On the other hand, no pt developed secondary graft failure. 5 pts (17%) developed acute GVHD with only 1 (4%) Grade IV aGVHD. 8 pts (29%) developed CMV reactivation within day 100 post-SCT. Full donor T-cell chimerism did not predict for GVHD or CMV reactivation. With longer follow up, some pts' have donor T-Cell chimerism increased with tapering of immunosuppressive therapy with or without GVHD or after receiving DLI. Conclusion: 1. Our preliminary data suggested that using a lower dose of Alemtuzumab (30 mg for RD and 60 mg for MUD) as GVHD prophylaxis is effective to prevent GVHD though still associated with high incidence of CMV reactivation. 2. Most pts achieve predominant Donor T cell chimerism on day 30 though many worsen on subsequent follow-up. 3. Although it appears that there's no impact on durability of engraftment, longer follow-up is required to determine the impact on relapse, chronic GVHD and survival. Disclosures: Fung: Genzyme: Honoraria. Off Label Use: Alemtuzumab for GVHD prophylaxis.

Chronic Graft-Versus-Host Disease after Allogeneic Stem Cell Transplant with in Vivo T-Cell Depletion By Alemtuzumab: Incidence, Outcome and Pattern of Organ Involvement

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3912-3912 ◽  
Author(s):  
Maria Chiara Finazzi ◽  
Cristina Boschini ◽  
Janice Ward ◽  
Charles Craddock ◽  
Alessandro Rambaldi ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Acute Gvhd ◽  
Stem Cell Transplant ◽  
Chronic Gvhd ◽  
Cell Depletion ◽  
Organ Involvement ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
T Cell Depletion

Abstract Introduction Graft-versus-Host Disease (GvHD) is one of the leading causes of mortality and morbidity following allogeneic stem cell transplant. In vivo T cell depletion by alemtuzumab as part of the transplant conditioning is an effective strategy to reduce the risk of GvHD. While it is recognised that the overall incidence of GvHD is reduced by alemtuzumab, the incidence of chronic GvHD as defined by the National Institute of Health (NIH) consensus criteria, the impact on outcome, and the pattern of organ involvement have not been defined yet in this transplant setting. Methods Consecutive patients (n = 323) undergoing allogeneic stem cell transplantation at the Queen Elizabeth Hospital, Birmingham, between January 1 2008 and June 30 2012 were reviewed in this retrospective, single centre study. Medical records were examined and data regarding the development of GvHD were collected; NIH consensus criteria for diagnosis and staging of chronic GvHD were stringently applied. Clinical characteristics of GvHD occurring in patients transplanted following T cell depletion by alemtuzumab administration (n=248) were compared with those of patients transplanted with a T cell replete graft (n=75). Patients receiving alemtuzumab were mainly treated with reduced-intensity conditioning protocols, while patients in the no-T-cell depletion group were mainly treated with a myeloablative, sibling transplant. Results After a median follow up of 38.4 months, the cumulative incidence (CI) of grade II-IV classic acute GvHD was 35% and 48% for patients transplanted respectively with or without T cell depletion by alemtuzumab (p= 0.041, Figure 1); with a CI of grade III-IV classic acute GvHD of 13% and 27% (p=0.007). The 2-years CI of grade II-IV late acute GvHD was not significantly different in the two groups (20% and 23% for patients respectively treated with or without alemtuzumab, p=0.589, Figure 2). T cell depletion by alemtuzumab significantly reduces the 3 years cumulative incidence of classic chronic GvHD (5% versus 31%, p<0.0001, Figure 3.A), but without a significant difference in the incidence of overlap syndrome between patients with and without T cell depletion (3 years CI respectively 6% and 7%, p=0.839, Figure 3.B). The pattern of organ involvement by classic acute GvHD was similar in patients with and without T cell depletion. The pattern of organ involvement by late acute GvHD in the alemtuzumab group was, however, significantly different compared to the T cell replete group (skin-gut-liver involvement reported respectively in 83%-28%-4% of patients and 56%-48%-20% of patients, p=0.003). Distribution of organ involvement by classic chronic and overlap syndrome was similar in the two groups; however, it seems that alemtuzumab prevents the development of lung GvHD (lung GvHD developed in 4 patients over the 75 patients of the no-T-cell depletion group, while none of the 248 patients transplanted with alemtuzumab experienced lung GvHD). In a multivariate analysis, the development of chronic GvHD was an independent predictor of higher mortality risk (HR 1.66, p = 0.04) and severe NIH global score at peak was confirmed as a poor prognostic factor for survival (HR 2.27, p=0.02). The negative impact of chronic GvHD and of the severe forms of chronic GvHD was independent of age and alemtuzumab administration. Conclusion This retrospective analysis provides for the first time data on the incidence rates of NIH-defined GvHD categories in patients transplanted after T cell depletion by alemtuzumab. Patients transplanted with alemtuzumab experienced a lower incidence of classic acute and classic chronic GvHD compared to patients not receiving T cell depletion. In contrast, alemtuzumab conditioning appeared to have no effect on the incidence of late acute GvHD or overlap syndrome, suggesting that these two entities of GvHD are driven by different immunological mechanisms as compared to classic acute and classic chronic GvHD. We also confirmed the utility of the NIH classification of GvHD and of the NIH global severity score to predict survival in alemtuzumab-conditioned allogeneic stem cell transplant. Disclosures No relevant conflicts of interest to declare.

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