Comparison of Outcomes After Allogeneic HSCT for Adult Patients with AML in Remission Using in the Conditioning Regimen Either I.V. Busulfex (BU) Plus Cyclophosphamide (Cy) or TBI Plus Cy: An- ALWP-EBMT Survey.

Abstract Abstract 195 TBI/CY and oral (p.o) Bu/Cy are the traditional allogeneic HSCT (alloHSCT) myeloablative conditioning regimens for adults with AML with comparable survival and relapse probabilities. Intravenous (i.v.) Bu in contrast to p.o Bu has more predictable pharmacokinetics and a more favorable toxicity profile. Post transplantation outcomes with i.v. Bu/Cy, thus, may be superior to those achieved with TBI/Cy. In order to address these issues, the ALWP of the EBMT performed a survey comparing i.v. Bu/Cy to TBI/Cy as conditioning regimen for adult pts. with AML undergoing alloHSCT. Overall, 603 alloHSCT were analyzed. One hundred pts. underwent alloHSCT with Bu/Cy while 503 with TBI/Cy. Age was 41 (range, 18–57) and 41 (range, 16–61) years and median transplant year was 2004 (2000 – 2005) and 2003 (2000 – 2005) for the Bu/Cy and TBI/Cy groups, respectively. Disease status at alloHSCT were CR1 – 81% vs. 78% and CR2–19% vs. 22% for the Bu/Cy and TBI/Cy groups, respectively. WBC count at diagnosis was 11×109/L and 15×109/L, respectively. Regarding the cytogenetic classification, 10% and 10% were good, 60% and 55% were intermediate and 9% and 6% were poor risk, respectively (data were NA for 21%–26% of pts). Sixty nine percent and 68% of both groups underwent alloHSCT from sibling donors, while 31% and 32% from MUD, respectively. Length of follow up was 37(15–86) and 57 (1–105) months for both groups, respectively. Sixty nine percent and only 41% of the Bu/Cy and TBI/Cy groups received PB, while 31% and 59% received BM grafts, respectively (p<0.0001). Engraftment was similar in the Bu/Cy vs. the TBI/Cy groups, 95% and 96%, respectively. Cumulative incidence of TRM at 2y was 17+4% and 23+2%, respectively (p=0.23). Acute GVHD (II–IV) was also similar between the 2 groups, 28% and 32%, respectively. Two year relapse incidence was 30+5% and 22+2% for Bu/Cy vs. TBI/Cy, respectively (p=0.03) while LFS was comparable 57+5% and 61+2%, respectively (p=0.5). In multivariate analysis Cy/TBI was found to be an independent good prognostic factor for reduce relapse rate (p=0.03, HR-1.67) and there was a trend for higher TRM (p=0.16). Poor prognostic factors for LFS and TRM were age >40y, disease status (CR2 vs. CR1) and MUD vs. Sib. donor. In conclusion, in this retrospective EBMT survey outcomes of alloHSCT in adult pts. with AML in CR using either i.v Bu/Cy or TBI/Cy were comparable. Disclosures: No relevant conflicts of interest to declare.

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Favourable Outcome of Non Myeloablative Allogeneic HSCT in Adult Patients with Severe Sickle Cell Disease: A Single Center Experience of 110 Patients

Blood ◽

10.1182/blood-2020-139348 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 1-2

Author(s):

Mohsen Alzahrani ◽

Bader Alahmari ◽

Ahmed Alaskar ◽

Ayman Hejazi ◽

Giamal Edin Gmati ◽

...

Keyword(s):

Graft Failure ◽

Conflicts Of Interest ◽

Conditioning Regimen ◽

Favourable Outcome ◽

Adult Patients ◽

Cell Disease ◽

Allogeneic Hsct ◽

Abo Incompatibility ◽

Moya Moya Disease

Background: Allogeneic HSCT for adult patients with sickle cell disease (SCD) is potentially curative but not commonly utilized therapy due to complications such as graft failure (GF) and organ toxicity. At our center, we adopted a non-myeloablative (NMA) conditioning regimen in adult patients with severe SCD. Herein, we are reporting our outcome data of up to 5-years of follow up post HSCT. Methods: Following IRB approval, adult patients that underwent HSCT from 2015 to 2020 for severe SCD with at least 6 months of follow up were included. Indications for HSCT were; presence of recurrent vaso-occlusive crisis (VOC), end organ damage, multiple joint AVN, recurrent priapism, transfusion dependency, or RBC alloimmunization. Conditioning regimen consisted of alemtuzumab (1 mg/kg divided over 5 days on days -7 to -3) and 300 cGy TBI on day -2 or -1. Pre-transplant preparation consisted of Hydroxyurea at maximum tolerated dose for 2-3 months. Peripherally mobilized stem cells targeting 10x106/kg of CD34 cells were used. For GVHD prophylaxis sirolimus was started on day -1 and continued for one year with tapering off if lymphoid chimerism is > 50%. EFS was defined as time from HSCT to graft failure or death from any cause whereas OS was defined as time from HSCT to death or last documented follow up. Results: A. Baseline Characteristics: A total of 110 patients were included with a median (range) age of 27 years (14-43), 59% of patients were male. Baseline median hemoglobin and hemoglobin S (HbS) was 95 g/L (64-121) and 74 % (17 -97), respectively. Regular hydroxyurea use was among 108 (98%) and 109 (99%) of patients required at least ≥ 1 transfusion annually. Narcotic pain killers were used regularly in 21 (19%) of patients. Median pre-HSCT ferritin was 1062 and iron chelation was used in 36 (33%). The most common indications for HSCT were (overlapping) recurrent VOC in 93%, ACS in 36%, stroke in 28% and RBC allo-immunization in 26%. Furthermore, 18 patients had 3 indications, 45 had 2 indications while the remaining 47 patients had one indication. Furthermore, 10 (9%) patients had Moya-Moya disease, 5 (5%) had sickling hepatopathy and or liver cirrhosis with total bilirubin up to 670 mmol/L and 1 (1%) patient had end stage renal disease on peritoneal-dialysis. A total of 61 (55%) donors were SC trait and underwent GCSF mobilization without major adverse events as previously reported (Damlaj et al., BMT 2018). 8 (7%) and 15 (14%) had major and minor ABO incompatibility, respectively. The remaining characteristics are found in table 1 B. Transplant Characteristics and Post HSCT Outcome: Median infused CD34x106/kg was 12.4 (6.4-24.9) and 108 (98%) patients had successful engraftment. A total of 12 patients experienced GF; 2 as primary and 10 as secondary within a median time of 129 days (40-583). Outcome post GF was as follows; recurrence of SCD in 6 (50%), aplastic bone marrow in 6 (50%) of whom 4 underwent a second allogeneic HSCT with Flu-Cy-ATG platform and all from MRD. Among second HSCT recipients, 3 are still alive and in SCD free disease status. Among patients with GF, 5 (42%) had minor ABO incompatibility while the remaining 7 (58%) were ABO matched HSCT. Mild acute skin GVHD (grade I to II) occurred in 3 cases and 4 cases developed autoimmune haemolytic anemia that resolved with steroids. Only one patient had CNS bleeding 2 years post-transplant in a background of history of stroke and Moya-Moya disease. A total of 53 (48%) patients successfully discontinued sirolimus while an additional 40 (35%) are on active taper. There were a total of 4 successful pregnancies in 3 patients; 3 pregnancies completed to term while 1 miscarried. Median follow up for the cohort is 16.8 (2-66) months. Estimated 2-year EFS and OS was 87.3% (+/- 0.036) and 97% (+/-0.017). All deaths were due to GF. There was no difference in outcome (EFS or OS) between patients receiving graft from normal vs. SC trait. Post HSCT Hb and chimerism results are shown in table 2. Conclusions: Herein, we present a large real-life experience demonstrating feasibility and favourable outcome of NMA HSCT in adult patients with severe SCD including patients with significant organ dysfunction or neurologic vasculopathy. Successful pregnancies and long-term discontinuation of immune suppression was possible. Longer follow up is warranted to ascertain stability of graft function over time. Disclosure: The authors declare they have no relevant conflicts of interest Disclosures No relevant conflicts of interest to declare.

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Transplant Conditioning Regimens and Outcomes After Allogeneic Hematopoietic Cell Transplantation (HCT) In Children and Adolescents with Acute Lymphoblastic Leukemia (ALL)

Blood ◽

10.1182/blood.v116.21.3506.3506 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3506-3506

Author(s):

James Tracey ◽

Mei-Jie Zhang ◽

Kathleen A Sobocinski ◽

Elizabeth L. Thiel ◽

Michael J. Eckrich ◽

...

Keyword(s):

Children And Adolescents ◽

Hematopoietic Cell Transplantation ◽

Conflicts Of Interest ◽

Lymphoblastic Leukemia ◽

Conditioning Regimen ◽

Disease Status ◽

Unrelated Donor ◽

Treatment Groups ◽

Conditioning Regimens ◽

Total Body

Abstract Abstract 3506 Recurrent disease is the most important cause of treatment failure after HCT. Total body irradiation (TBI)-containing conditioning regimens are associated with fewer relapses and longer leukemia-free survival (LFS) in children and adolescents with ALL. While TBI <13 Gy + cyclophosphamide (Cy) is considered standard, attempts to lower relapse rates have led to addition of a second chemotherapeutic agent (etoposide) or higher dose TBI (≥13 Gy) with or without addition of etoposide. TBI dosing (<13 Gy vs. ≥13 Gy) or the addition of etoposide to TBI + Cy regimen has not been examined in children. We report on 765 patients aged <18 years, who received either an HLA-matched sibling (n=160) or an unrelated donor (URD, n=605) HCT between 1998 and 2007. Seventy percent of patients were in 2nd complete remission (CR), 20% were in 3rd CR, and the remaining 10%, in relapse at HCT. The median age of the study population is 9 years and the median follow-up of surviving patients is 4 years. Transplant outcomes were examined in four treatment groups: 1) TBI <13 Gy + Cy (n=304), 2) TBI <13 Gy + Cy + etoposide (n=108), 3) TBI ≥13 Gy + Cy (n=327), and 4) TBI ≥13 Gy + Cy + etoposide (n=26). Ninety-six percent of patients in the TBI <13 Gy group received 12 Gy and 4%, 10 Gy. Irradiation doses in the TBI ≥13 Gy group were 13.2 Gy (24%), 13.5 Gy (41%) and 14 Gy (35%). Patient and disease characteristics (performance score, disease status, NCI-risk score, duration of first remission and cytogenetic risk) were similar among the treatment groups. The 3-year probabilities (95% confidence interval) of treatment-related mortality (TRM), relapse, and LFS in the four treatment groups are shown in the Table below. Neither higher dose TBI (≥13 Gy) nor the addition of etoposide regardless of TBI dose was associated with lower risks of leukemia recurrence or longer LFS after HCT. In the absence of an advantage for leukemia control, further intensification of the conditioning regimen TBI <13 Gy + Cy is not recommended. TRM Relapse LFS 1) TBI dose <13 Gy + Cy 25 (21–31)% 30 (24–35)% 45 (39–51)% 2) TBI dose <13 Gy + Cy + etoposide 29 (21–38)% 26 (18–34)% 45 (35–54)% 3) TBI dose ≥13 Gy + Cy 23 (19–28)% 33 (28–39)% 43 (38–49)% 4) TBI dose ≥13 Gy + Cy + etoposide 35 (17–52)% 31 (15–69)% 35 (17–52)% Disclosures: No relevant conflicts of interest to declare.

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HLA-Haploidentical TCR αβ/CD19-Depleted Hematopoietic Stem Cell Transplantation in Children with Fanconi Anemia

Blood ◽

10.1182/blood.v128.22.2287.2287 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2287-2287

Author(s):

Luisa Strocchio ◽

Pietro Merli ◽

Alice Bertaina ◽

Luciana Vinti ◽

Letizia Pomponia Brescia ◽

...

Keyword(s):

B Cells ◽

Fanconi Anemia ◽

Conflicts Of Interest ◽

Chronic Gvhd ◽

Conditioning Regimen ◽

Unrelated Donor ◽

Post Transplantation ◽

Hematopoietic Stem ◽

Increased Risk

Abstract Introduction. Allogeneic HSCT currently represents the only consolidated curative approach for Fanconi anemia (FA) patients, with best results observed in the HLA-identical sibling setting. For patients lacking an HLA-matched related or unrelated donor, haploidentical HSCT virtually assures the opportunity for nearly all patients to benefit from HSCT, offering the advantage of immediate accessibility to the transplant procedure. In order to overcome the limitation of delayed immune recovery, historically associated with this type of allograft, in the last few years we developed a novel method of ex vivo graft manipulation, consisting of the negative depletion of T-cell receptor (TCR) αβ+ T-lymphocytes and CD19 B-cells from peripheral blood stem cells (PBSC) grafts (ClinicalTrial.gov identifier: NCT01810120) (Bertaina el al., Blood 2014). Here we report our analysis in a subgroup of FA patients given TCRαβ/CD19-depleted haploidentical HSCT at our Institution. Patients and methods. Ten consecutive FA patients (6 girls and 4 boys) underwent a TCRαβ/CD19-depleted HSCT from an HLA-haploidentical relative between September 2011 and July 2015. Median age at diagnosis was 6.6 (range 2.7-22.0) years and median age at time of transplantation was 8.1 (range 4.4-22.2) years. The conditioning regimen included Cyclophosphamide 300 mg/m2/day and Fludarabine 30 mg/m2/day for 4 consecutive days (days -6 to -3), with 200 cGy single-dose TBI. Pretransplantation Fresenius® ATG was administered at a dose of 4 mg/kg/day for 3 consecutive days (days -5 to -3) in order to prevent both graft failure and graft-versus-host disease (GVHD). All patients received Rituximab 200 mg/m2 to reduce the risk of Epstein-Barr virus-related post-transplant lymphoproliferative disorders. Selective removal of TCRαβ+ and B-cells was performed on G-CSF-mobilized donor PBSC through labeling with biotinylated anti-TCRαβ antibodies and anti-CD19 antibodies, followed by incubation with anti-biotin antibodies conjugated to paramagnetic beads (CliniMACS; Miltenyi Biotec, Bergisch Gladbach, Germany). No immunosuppressive therapy was administered as post-transplantation prophylaxis against GVHD. Results. The TCRαβ/CD19-depletedgrafts contained a median of 20.40 x106/kg (range 15.80-33.40) CD34+ cells, 5.60 x106/kg (range 1.78-69.60) CD3+ lymphocytes, 0.021 x106/kg (range 0.002-0.043) TCRαβ+ lymphocytes, 5.60 x106/kg (range 1.78-69.60) TCRγδ+ lymphocytes, 0.036 x106/kg (range 0.013-0.079) CD20+ lymphocytes, and 45.30 x106/kg (range 16.2-177.0) NK cells. Engraftment with sustained full donor chimerism was achieved in 9 out of 10 patients, the cumulative incidence of graft rejection being 10% (95% CI, 0-26.8). The patient who rejected his first allograft achieved a complete engraftment after a second HSCT from one-antigen mismatched unrelated donor. No secondary graft failures were observed. The median time for neutrophil and platelet engraftment was 12 days (range, 9-15) and 9 days (range, 8-12), respectively. No patient experienced acute or chronic GVHD in the follow-up period. No transplant-related deaths occurred in our cohort. With a median follow-up of 28 months (range 13.2-39.1), the Kaplan-Meier estimates of OS and DFS were both 100%, while the EFS probability was 90% (95% CI, 47.3-98.5). Discussion. These data suggest that haploidentical HSCT after removal of TCRαβ+ and CD19+ lymphocytes is able to guarantee engraftment with excellent OS and DFS in patients affected by FA. Moreover, given the very low incidence of both acute and chronic GVHD, which has been shown to contribute to the increased risk of developing late post-transplantation malignancies in FA patients, this approach can be considered a very attractive option for FA patients in need of an allograft and lacking an HLA-identical family donor. Disclosures No relevant conflicts of interest to declare.

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Antithymocyte Globulin Improves the Survival of Patients with Myelodysplastic Syndrome Undergoing HLA-Matched Unrelated Donor and Haplo-Identical Donor Transplants

Blood ◽

10.1182/blood.v128.22.5851.5851 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5851-5851

Author(s):

Miao Miao ◽

Hong Wang ◽

Hong Liu ◽

Jinyi Zhou ◽

Tongtong Zhang ◽

...

Keyword(s):

Antithymocyte Globulin ◽

Median Overall Survival ◽

Conflicts Of Interest ◽

Conditioning Regimen ◽

Unrelated Donor ◽

Matched Unrelated Donor ◽

The Past ◽

Conditioning Regimens ◽

Matched Sibling

Abstract Background: Significant advances have been achieved in the outcomes of patients with myelodysplastic syndromes (MDS) after both HLA-matched sibling donor transplants (MSDT) and non-MSDT in the past few years, the latter including HLA-matched unrelated donor (MUDT) and haplo-identical donor transplants (HIDT). Methods: We retrospectively analyzed the data of 85 consecutive patients with MDS who received allogeneic HSCT between Dec 2007 and Apr 2014 in our center. These patients comprised 38 (44.7%) who received MSDT, 29 (34.1%) MUDT, and 18 (21.2%) HIDT. Results: The median follow-up was 30.0 months. Over all, the median overall survival (OS) was 60.2 months and the probabilities of OS at the first, second and fifth year were 63%, 57% and 48%, respectively. Median OS post transplant (OSPT) was 57.2 months and the probabilities of OSPT at the first, second and fifth year were 58%, 55% and 48%, respectively. Relapses occurred in 16 patients (18.8%), and the cumulative incidence of relapse at the first, second and third year were 14%, 23% and 27%, respectively. The survival of patients receiving non-MSDT was superior to that of MSDT, median OSPT being 84.0 months and 23.6 months, respectively (P=0.042); And the similar result was observed when we analyzed the OS of patients who underwent non-MSDT or MSDT (median OS: 120 months vs. 27.0 months; P=0.028). We also found that using antithymocyte globulin (ATG) in conditioning regimens significantly improved survival after non-MSDT, with better OS and OSPT (P=0.016 and P=0.025). Furthermore, we compared OS or OSPT of patients who received non-MSDT with ATG (n=38) and MSDT without ATG (n=37). Our results showed that using ATG in conditioning regimen significantly improved survival of non-MSDT, with better OSPT (median OS: 84.0 months vs. 23.0 months; P=0.026) and OS (median OS: 120 months vs. 25.1 months; P=0.016). Conclusions: These data suggest that, non-MSDT could be a valid alternative when MSDT is not available, and ATG may improve the survival of MDS patients after non-MSDT. Disclosures No relevant conflicts of interest to declare.

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Multicenter Retrospective Analysis of Second Allogeneic HSCT Outcomes for Hematologic Malignancies in Korea.

Blood ◽

10.1182/blood.v114.22.4298.4298 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4298-4298

Author(s):

Kyoung Ha Kim ◽

Dong Hwan Dennis Kim ◽

Jun Ho Jang ◽

Kihyun Kim ◽

Chul Won Jung ◽

...

Keyword(s):

Conflicts Of Interest ◽

Cord Blood Transplantation ◽

Conditioning Regimen ◽

Hematologic Malignancies ◽

Hematopoietic Stem ◽

Allogeneic Hsct ◽

Blood Transplantation ◽

Primary Disease ◽

Insurance Reimbursement ◽

Conditioning Regimens

Abstract Abstract 4298 Background Increasing number of autologous or allogeneic HSCT in Korea in this decade resulted in increasing requirement for second allogeneic hematopoietic stem cell transplantation (HSCT) as a result of the recurrence of primary disease or graft failure. Since Dec 2008, second HSCT has been approved by Korean government to be covered by national health insurance reimbursement system. However, there is no available data on the transplant outcomes following second allogeneic HSCT in Korea. Accordingly, the current study attempted to analyze the outcome of second allogeneic HSCT retrospectively. Methods Transplant data were collected retrospectively from 8 transplant centers in Korea. Inclusion criteria are as follows. 1) Age equal or over 15 years old, 2) Hematologic malignancies excluding aplastic anemia, PRCA, PNH or solid tumor, 3) Patients who underwent second alloHSCT receiving cord blood transplantation (CBT). Results Sixty four pts were included with following diagnoses: AML (n=28), ALL (n=5), CML (n=3), lymphoma (n=22), myeloma (n=5), and others (n=1). The median age was 37 (range 16-65). The first transplantation had been performed with autologous (59.4%) or allogeneic (40.6%) donors. The donors for second HSCT were HLA-identical sibling 32(47%), unrelated 28(49%), or haploidentical donor 2(4%). Conditioning regimen included TBI-based myeloablative 6(9%), non TBI myeloablative 19(30%), or reduced intensity regimen 38(60%). With median 16 months of follow up (range, 3 to 93 months), 40 pts died of transplant related toxicity (n=28; 70%), recurrence of primary disease (n=9; 22.5%) or other (n=3; 7.5%). After second HSCT, 56% were in complete remission, 38% in partial remission, and 6% were refractory. The 1- and 2- year overall survival rate was 42% and 29%, respectively. Conclusion The patients received non TBI conditioning regimens were shown longer survival. Disclosures: No relevant conflicts of interest to declare.

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A Sensitive Replicate RQ-PCR of BCR ABL Transcripts Suggests That A Large Portion of Long Term Post Allogeneic SCT CML Patients Are in Deep MR and May Therefore Be Cured From Their Disease

Blood ◽

10.1182/blood.v120.21.1690.1690 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1690-1690

Author(s):

Maya Koren-Michowitz ◽

Avichai Shimoni ◽

Filomena Daraio ◽

Francesca Crasto ◽

Roberta Lorenzatti ◽

...

Keyword(s):

Median Time ◽

Kinase Inhibitor ◽

Conflicts Of Interest ◽

Conditioning Regimen ◽

Chronic Phase ◽

Disease Status ◽

Molecular Response ◽

Transcript Levels

Abstract Abstract 1690 RQ-PCR has become the major method for the follow up of CML pts in the tyrosine kinase inhibitor (TKI) era. In CML pts undergoing allogeneic SCT (Allo-SCT) it has been shown that successive increase in quantitative BCR ABL transcript levels is in correlation with the clinical outcome and may serve as an early sign of disease relapse and an indication for a therapeutic intervention such as the addition of a TKI or DLI. However, the sensitivity of current RQ-PCR methods which is limited to approximately 10−4 in the majority of routine clinical laboratories, do not allow for the detection of very low BCR ABL transcript levels, and therefore RQ-PCR negativity cannot be regarded as CMR in the majority of pts. Studies of replicate RQ-PCR (rRQ-PCR) have shown that the number of measurement repetitions is relevant in the detection of rare transcripts and rRQ-PCR was found to be more sensitive than conventional RQ-PCR in TKI treated CML pts. We evaluated the role of rRQ-PCR in the detection of MRD in a cohort of long term post Allo-SCT CML patients. Samples from 12 CML pts (M=7, F=5), median age 43 y, at a median time of 85 months after SCT (range 28–136) were tested. SCT was myeloablative (n=6) or with RIC (n=6), from a matched sibling (n=7) or a MUD (n=5), in first chronic phase (CP1) (n=8) or at a later phase (n=4). rRQ-PCR was done in 82 replicates using the same conditions of conventional RQ-PCR. Results of rRQ-PCR are given in Table 1. 75% of the patients had negative RQ-PCR in all 82 wells, while 3 patients had positive results in 1 (1.2%), 2 (2.4%) and 6 (7.3%) wells, respectively, which was above the background determined in normal PB samples (6/901 positive wells, 0.66%). The sensitivity of rRQ-PCR was 10−5.5 or higher in all patients. Negative rRQ-PCR result was not related to the phase at SCT (CP1 vs. others), conditioning regimen (myeloablative vs. RIC), donor type (sibling vs. MUD) or the presence of GVHD. Median time from diagnosis to SCT was borderline longer in patients with positive rRQ-PCR results (61 vs. 25 months, p=0.08). Higher sensitivity RQ-PCR methods are able to further define subgroups of post BMT CML pts and allow for a more accurate follow up of MRD. We will present update clinical data at 1 year after rRQ-PCR determination. Table 1. Results of rRQ-PCR. Patient number Disease status at SCT Conditioning Time from diagnosis to SCT (months) Time from SCT to rRQ-PCR (months) rRQ-PCR result BCR ABL/ABL1 (IS) Total quantity of ABL transcripts Level of MR 1 AP RIC 97 57 0 575034.8 MR5.5 2 CP2 MA 6 30 0.0000862 705622.3 3 CP2 MA 273 48 0.0007393 563237.5 4 CP1 RIC 4 52 0 997521.8 MR6 5 CP1 MA 16 34 0 555768.9 MR5.5 6 CP1 MA 39 30 0 700630.1 MR5.5 7 CP1 MA 6 40 0 874247.9 MR5.5 8 CP1 RIC 61 68 0.0000484 1067353 9 CP1 RIC 33 46 0 938046.4 MR5.5 10 CP1 RIC 18 58 0 1467748 MR6 11 AP RIC 6 28 0 776271.9 MR5.5 12 CP2 MA 3 23 0 860350.6 MR5.5 RIC reduced intensity conditioning; MA myeloablative conditioning; MR molecular response. 1 Average result of positive wells normalized to the international standard. PCR positive in 12, 63 and 24 wells of 82 tested. Disclosures: No relevant conflicts of interest to declare.

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Nonmyeloablative Allogeneic Stem-Cell Transplantation for Hematologic Malignancies: A Systematic Review

Cancer Control ◽

10.1177/107327480301000104 ◽

2003 ◽

Vol 10 (1) ◽

pp. 17-41 ◽

Cited By ~ 21

Author(s):

Benjamin Djulbegovic ◽

Jerome Seidenfeld ◽

Claudia Bonnell ◽

Ambuj Kumar

Keyword(s):

Stem Cell ◽

Case Series ◽

Disease Status ◽

Hematologic Malignancies ◽

Cell Transplants ◽

Unrelated Donors ◽

Conditioning Regimens ◽

Prospective Case Series ◽

Patient Selection Criteria

Background Increasingly, clinicians advocate the use of nonmyeloablative allogeneic stem-cell transplants (NM-allo-SCTs, “mini-transplants”) to manage hematologic malignancies. They hypothesize that NM-allo-SCT is equally efficacious to standard allo-SCT but produces less regimen-related toxicity. Methods To analyze available evidence on the benefits and harms of “mini-transplants,” we identified 23 manuscripts, 1 abstract, and 1 letter that reported the outcome of mini-transplants in hematologic malignancies. Results Data were compiled on 603 treated patients, with 118 transplants using stem cells from matched unrelated donors. All studies were small prospective case series, and most lacked concurrent or historical controls. Outcomes of interest were not uniformly reported. The studies were heterogeneous and used different patient selection criteria, conditioning regimens, and timing of transplant with respect to disease status. The transplant-related mortality rate was 32%, the relapse rate was 15%, and toxicities included acute and chronic graft-vs-host disease and veno-occlusive disease. The aggregate rate of complete remission was 45%. Survival at 1 year or longer ranged from 30% to 60% at 1 to 5 years of follow-up. All studies reported successful chimerism. Conclusions Disease-specific studies with longer follow-up are needed to evaluate this potentially promising therapy.

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Results of T Cell Depleted (TCD) Myeloablative Hematopoietic Stem Cell Transplants (HSCT) in Patients with Hematologic Malignancies ≥ 55 yrs of Age.

Blood ◽

10.1182/blood.v106.11.3660.3660 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3660-3660

Author(s):

Ann A. Jakubowski ◽

Esperanza B. Papadopoulos ◽

Hugo R. Castro-Malaspina ◽

Katharine Hsu ◽

Miguel-Angel Perales ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Hematopoietic Stem Cell ◽

High Risk Patient ◽

Disease Status ◽

Unrelated Donor ◽

Hematopoietic Stem ◽

Conditioning Regimens ◽

Good Risk

Abstract Allogeneic HSCT remains the only curative therapy for many patients(pts) with hematologic diseases. Studies have suggested that older pts experience greater toxicity from the intensive chemo-radiotherapy used in myeloablative conditioning regimens. As a consequence, many older pts are now offered non-myeloablative transplants (NMAT) for malignant conditions where a graft vs. tumor effect (GvT) is expected to provide the antitumor effect in place of the chemo-radiotherapy. Unfortunately, graft vs. host disease (GvHD) remains a common occurrence after conventional transplants, occurring more frequently in older pts and unrelated donor transplant recipients, resulting in significant morbidity and mortality. Furthermore, the efficacy of NMAT is limited by the disease status at time of transplant and by the susceptibility of the hematologic disease to a GvT effect. TCD of hematopoietic stem cell grafts offers an alternative to older pts, in particular those requiring unrelated donor transplants (URD), with the advantage of a reduced incidence of GvHD. From 1995–2005, 57 patients ≥55 yrs received myeloablative TCD transplants at our institution. The median age was 58.2 (range 55–69.2) yrs. Stem cell sources were TCD bone marrow, PBSC or both. Thirty-seven received transplants from related donors (RD), including two mismatched, and 20 received transplants from unrelated donors (URD), 9 of whom were mismatched. In addition to their advanced age, many of these pts were considered high risk based on the status of disease, HLA mismatch, and history of previous therapy. Twenty-three pts were considered “good risk” by disease status (CML-CP1, AML-CR1, CR2) and 34 pts were considered poor risk (>CML-CP1, >AML CR2, MDS, NHL, >ALL CR1, ABL.) BM was TCD by soybean agglutination followed by sheep red blood cell rosetting (E), and PBSCs by CD34+ selection and E-rosetting. Conditioning regimens included total body irradiation (TBI) in addition to thiotepa and cyclophosphamide, or thiotepa and fludarabine. The non-TBI preparative regimen consisted of busulphan, melphalan and fludarabine. Anti-thymocyte globulin was used as rejection prophylaxis for all TCD transplants until 2001 when it was eliminated from the TBI containing regimen for matched RD transplants. A total of 25 pts (15 matched RD and 10 URD, 6 of whom were mismatched) are alive following TCD transplants with a median follow up of 24 mos. for RDs and 12 for URDs. Of the survivors, 2/10 URD and 14/15 RD recipients received TBI containing regimens based on the triage system at our center. Three pts with CML-CP1, one with CML-acc and one with AML-CR1 showed evidence of minimal residual disease, received donor leukocyte infusions and subsequently achieved longterm continued CR. The incidence of post-transplant GvHD was low despite the high number of mismatched URD transplants - 1 Grade IV (RD), 2 Grade 3 and 1 Grade 1 (URD). The 100 day mortality was 15%. Overall and current disease free survival for ‘good risk’ patients based on disease status is 58% for RD and 60% for URD. Although longer follow up is necessary to confirm these results, the promising DFS rates in association with a low incidence of GvHD in this older and relatively high risk patient population support further investigation of myeloablative TCD HSCT in these patients.

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Durable Remission with Decreased HTLV-I Proviral Load after Reduced-Intensity Stem Cell Transplantation (RIST) in Patients with Adult T-Cell Leukemia/Lymphoma (ATL).

Blood ◽

10.1182/blood.v106.11.3347.3347 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3347-3347

Author(s):

Ryuji Tanosaki ◽

Kisato Nosaka ◽

Shin Mineishi ◽

Shin-ichiro Mori ◽

Sung-Won Kim ◽

...

Keyword(s):

Conditioning Regimen ◽

Disease Status ◽

Donor Lymphocyte Infusion ◽

Acute Type ◽

Adult T Cell Leukemia ◽

Trial Testing ◽

Grade Ii ◽

Related Donor ◽

Healthy Carriers

Abstract Background. ATL is an HTLV-I-associated hematological malignancy. The majority of ATL patients are not curable using current chemotherapy with median survival time of 13 months. Recently, patients undergoing allo-SCT with conventional conditioning regimen were reported to have a 3-year overall survival (OS) rate of 45%, however, with high transplant-related mortality (TRM) rate as much as 40% (Fukushima T. Leukemia19:829, 2005). Since most ATL patients are over 50 years old with various complications, limited numbers of patients are eligible for conventional transplant. We have already conducted a phase I multi-center trial testing the feasibility of RIST in ATL patients, where 2-year OS was 33% and some differences in the outcome were suggested among participating institutes. Hence, we investigated the efficacy of RIST performed exclusively in our single institute (NCCH, Japan). Patients and Methods. Between Oct 2000 and Jun 2005, 16 ATL patients underwent RIST from a related donor. Since 3 have been enrolled into an on-going multi-center trial, 13 patients were analyzed in this retrospective study, including 3 who were enrolled into the above-mentioned multi-center trial (Okamura J. Blood105;4143, 2005). Median age was 51 years old (range, 44–61), 8 males and 5 females, and 8 were of acute type and 5 of lymphoma. The disease status at transplant was 3 CR, 7 PR and 3 primary refractory. Three donors were HTLV-I healthy carriers. Eleven were HLA 6/6, 2 were 5/6, 12 were PBSCT and 1 was BMT. Conditioning regimen was fludarabine 30 mg/m2 x6, busulfan 4 mg/kg x2 with (n=5) or without (n=8) rabbit ATG 2.5 mg/kg x2. Prophylaxis of GVHD was CSP alone. Results. Engraftment was rapid (median, 11 days) in all cases, and there was no TRM. Acute GVHD of grade II–IV developed in 7, and chronic extensive GVHD in 5. Eleven patients achieved CR after RIST, and 6 relapsed or progressed, among whom 2 achieved CR after cessation of CSP, donor lymphocyte infusion and local irradiation, and have been disease-free for more than 1 year. Ten patients are alive, 9 without disease, with median follow-up time of 26 mos (range, 4–45 mos). HTLV-I proviral titers determined using real time PCR decreased after RIST and became undetectable in 8 out of 13 patients. In 3, including one transplanted from an HTLV-I carrier donor, anti-HTLV-1 antibody transiently decreased and became nearly undetectable. Conclusions. RIST is feasible and safe in ATL patients, and it has not only an anti-ATL but also an anti-HTLV-I activity. This is the first report documenting the efficacy of RIST for ATL in terms of survival and remission durability. Figure Figure

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T Cell Depletion with Alemtuzumab Is Associated with a High Incidence of EBV Viraemia but Low Risk of PTLD Following Allogeneic Stem Cell Transplantation

Blood ◽

10.1182/blood.v112.11.1177.1177 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1177-1177

Author(s):

Ben Carpenter ◽

Maria Dimopoulou ◽

Nilusha Manji ◽

Tanzina Haque ◽

Claire Atkinson ◽

...

Keyword(s):

T Cell ◽

Post Transplantation ◽

Allogeneic Hsct ◽

Ebv Reactivation ◽

Unrelated Donors ◽

Ebv Dna ◽

High Level

Abstract Re-activation of latent EBV infection is a significant risk following T-cell depleted (TCD) allogeneic HSCT. The clinical course can range from asymptomatic viraemia to the development of post-transplantation lymphoproliferative disease (PTLD) and death. Since alemtuzumab depletes both T and B cells, it has been proposed that the risk of PTLD will be reduced compared to other TCD protocols. In an attempt to determine the risk of EBV viraemia or PTLD following allogeneic HSCT employing alemtuzumab-containing conditioning protocols, we reviewed outcomes in 91 consecutive adult patients treated at our institution. Of these, 84 patients had >6 months follow-up and are included in this analysis. Two strategies of TCD were employed in this cohort: in vivo TCD with alemtuzumab (median dose 100mg) as part of a reduced intensity regimen (fludarabine based n=51); and in vitro TCD of the PBSC graft with 20 mg alemtuzumab ‘in the bag’ following conventional myeloablative conditioning (n=33). We have shown previously that alemtuzumab antibody levels persist for longer periods (up to 8 weeks ) following this in vivo depletion strategy compared to the in vitro approach [Morris et al. Blood 2003 102:404–6]. The median follow-up is 337 days and median age was 43 years (range 16–67 years). Diagnoses were AML/MDS (n=39), NHL (n=16), Hodgkins lymphoma (n=11), MPD (n=7), CLL (n=5) and other (n=6). 41/84 had HLA-identical sibling donors, 2 mismatched sibling donors, 21 matched unrelated donors and 20 mismatched unrelated donors. Monitoring for EBV load was performed by TaqMan whole blood real time PCR on a weekly basis for 100 days post transplantation and then as seen for follow-up. Positive results defined as >200 copies/ml of EBV DNA. All patients with high levels of EBV viraemia (EBV DNA level > 40,000 copies/ml) underwent CT imaging, bone marrow examination and lumbar puncture followed by withdrawal of immunosuppression and a single infusion of 375mg/m2 Rituximab as per institution policy. Of 82 patients where serostatus was available, 92.7 % were anti-EBV IgG positive. The 12-month cumulative incidence (CI) of EBV reactivation was 34.5% (39.2% following in vivo TCD versus 27.3% following in vitro TCD, p=0.2). Median peak viral load was 1,922 copies/ml (range 205–6,210,000). The 12 month CI of high-level EBV viraemia (>40,000 copies/ml) was 11.9% (7.84% following in vivo TCD versus 18.2% following in vitro TCD, p=0.19). Patients re-activated EBV at a median of 86 days post transplant (range 21–380 days). The median duration of viraemia was 42 days (range 1–460 days). The 12-month CI of recurrent EBV re-activation (>1 episode) was 21.4% (15.5% following in vivo TCD versus 25.5% following in vitro TCD, p=0.4). Of 10 patients with high-level EBV viraemia, 1 patient had PTLD as confirmed by histology. 8 of 10 patients received a single dose of Rituximab and this was associated with a rapid decline in EBV DNA load to undetectable levels in all cases. No adverse events secondary to Rituximab were noted. The patient with PTLD was given a second dose of Rituximab and attained a CR that persists at 334 days post treatment. 12-month non-relapse mortality was 10% in patients who had EBV reactivation and 27.7% in patients without EBV reactivation (p=0.06). Baseline and post-transplantation characteristics of sex, age, diagnosis, in vivo vs. in vitro alemtuzumab, donor type, CMV viraemia and presence of past or active acute GVHD were not related to re-activation of EBV by uni- or multivariate analysis in this patient cohort. In summary, this report demonstrates that TCD using alemtuzumab-containing conditioning protocols is associated with a high frequency of EBV viraemia but low risk of PTLD or non-relapse death in a cohort of patients treated pre-emptively with Rituximab for high EBV DNA loads.

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