Case of a Patient with Progressive Adult T-Cell Leukemia/Lymphoma Treated Successfully by Reduced-Intensity Conditioning Stem Cell Transplantation from an HLA-Incompatible Related Donor

2005 ◽  
Vol 82 (4) ◽  
pp. 357-361 ◽  
Author(s):  
Hiroshi Fujiwara ◽  
Hideaki Kawada ◽  
Kakushi Matsushita ◽  
Heiichiro Hamada ◽  
Atsuo Ozaki ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cell Leukemia ◽  
Reduced Intensity Conditioning ◽  
Adult T Cell Leukemia ◽  
Related Donor ◽  
Hla Incompatible ◽  
Reduced Intensity

A Pilot Study of Reduced-Intensity Conditioning Stem Cell Transplantation with T-Cell Replete HLA-Mismatched Allograft from Child to Parent Patient for the Treatment of Refractory Adult T-Cell Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5406-5406
Author(s):  
Hiroshi Fujiwara ◽  
Atsuo Ozaki ◽  
Makoto Yoshimitsu ◽  
Heiichiro Hamada ◽  
Hideaki Kawada ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Pilot Study ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Induction Chemotherapy ◽  
Cell Leukemia ◽  
Reduced Intensity Conditioning ◽  
Adult T Cell Leukemia ◽  
Reduced Intensity

Abstract [Background/Purpose] Adult T-cell leukemia (ATL) is a most aggressive lymphoid malignancy with poor prognosis, and at present, allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been an only curative modality. Nevertheless, not only the aggressive nature of disease itself, but also the aging of patients older than 55 y.o. contribute to therapeutic impediments by comorbidity and difficulty of timely acquiring HLA-matched sibling donor. In this setting, allograft from child to parent patient is a realistic modality. We report a result of a prospective study evaluating the efficacy of reduced -intensity conditioning SCT (RIST) with HLA-mismatched allograft from child to parent for ATL patients. [Patients/methods] 5 patients (2 males, and 3 females) with ATL in progressive disease (PD) after induction chemotherapy with LSG15 regimen who had no HLA-identical sibling donors were enrolled. Patient median age was 59 y.o. All donors were sons with haploidentical HLA. Median age of donor was 29 y.o. KIR ligands were matched. Preparatory regimen consisted of fludarabine (180mg/m2), busulfan (8mg/m2) or cyclophosphamide (120mg/kg) and rabbit antithymocyte globulin (2.5mg or 5.0mg/kg). Stem cell source was G-CSF mobilized PBSC. Mean infused CD34 cell number was 8.3×106/kg (from 4.1 to 23.3 × 106/kg). GVHD prophylaxis consisted of tacrolimus or cyclosporine and short term methotraxate and mycophenolate mofetil. [Results] Median interval from induction chemotherapy to transplantation was 5 months. Median observation interval was 8 mo. (from 3.5 mo. to 31 mo.). All 5 cases had neutrophil engraftment at day 15 after transplantation. In 5 of 5 cases, complete donor T-cell chimerism were obtained by day 30. Overall survival (OS) and progression free survival (PFS) at 1 year was 50%, and 26.7%, respectively. Evaluation of peripheral residual disease demonstrated by HTLV-I proviral load and soluble interleukin-2 receptor (sIL-2R) value documented the strong disease suppression by this transplants. Analysis of NK cell kinetics revealed that donor-derived NK cells expanded and exerted killing activity mainly until 4 months after transplantation, and decreased in number thereafter. These findings indicated all achieved complete donor T-cell chimerism followed by clinical observations for graft vs. ATL effect. Although, disease progression occurred 4 of 5 cases, 2 achieved remission again with the longest response duration of 31 mo. All but UPN2 experienced GVHD (grade 2 to 4), and UPN2 had early relapse and died of ATL at 4 mo. after allo-HSCT. Frequent reactivations of cytomegalovirus were observed, but well controlled by ganciclovir. [Summary] In our pilot study, RIST with T-cell replete HLA-mismatched allograft from child to parent patient could provide timely donor acquisition and durable remission for all patients with refractory ATL. This setting may be one of realistic modalities for ATL patients who need alternative donors.

Favorable Outcome of Reduced-Intensity Stem Cell Transplantation for Adult T-Cell Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4480-4480
Author(s):  
Fumie Iwai ◽  
Hitomi Kaneko ◽  
Goichi Tatsumi ◽  
Tadahiko Matsumoto ◽  
Shinya Inada ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Favorable Outcome ◽  
Acute Type ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
Reduced Intensity

Abstract Abstract 4480 Introduction: Adult T-cell leukemia (ATL) endemic in southwestern Japan is an HTLV-I-induced mature T-cell neoplasm. It has a dismal prognosis when treated with conventional chemotherapy, mainly because ATL cells overexpress multidrug-resistance genes. Allogeneic hematopoietic stem cell transplantation (allo-SCT) has been reported to improve the prognosis. However, it is also known that allo-SCT shows high treatment-related mortality (TRM) because of disease characteristics of severely deteriorated cellular immunity. Therefore, we evaluated the outcome of reduced-intensity stem cell transplantation (RIST), compared to conventional stem cell transplantation (CST) for ATL patients (pts). Patients and methods: We retrospectively analyzed consecutive 20 pts with aggressive ATL (acute type, 16; lymphoma type, 4) who underwent allo-SCT between 2000 and 2010 in our institute. The age of pts who received RIST was significantly older than that of CST (P = <.001). The other parameters were balanced between the two groups (Table 1). All pts received induction chemotherapy with Japan Clinical Oncology Group (VCAP-AMP-VECP) regimen or biweekly CHOP prior to SCT. Nine pts received a conventional myeloablative conditioning with CY/TBI-based (n=8) or BU/CY-based (n=1) regimens and 11 pts received a reduced-intensity regimen with fludarabine(Flu)/melphalan(Mel)±TBI (Flu 25 mg/m2 on days -6 to -2 + Mel 40 mg/m2 on days -4 and -3 ± TBI 4 Gy on day -1). Graft-versus-host-disease (GVHD) prophylaxis consisted of cyclosporine plus short-term methotrexate (sMTX) for HLA-matched sibling donor recipients and tacrolimus plus sMTX for the others. Cyclosporine or tacrolimus was promptly tapered when complete chimerism was achieved. Results and discussion: The estimated 3-year overall survival (OS) and 3-year progression-free survival (PFS) rates for all pts were 59% and 55%, respectively (Fig. 1). At the median follow-up duration of 25 months (1–67), 12 pts were alive and 8 pts dead. Causes of death were disease progression (n=4) and treatment-related complications including acute GVHD and infection (n=4). The cumulative incidences of disease-associated mortality and TRM at 3 years were 21% and 20%, respectively. Importantly, after 1 year post-transplantation, the curve of PFS reached plateau phase. Therefore, allo-SCT could be a curable therapeutic option for aggressive ATL. It is notable that RIST showed excellent 3-year OS. Although not significant, 3-year OS for RIST and CST were 70% and 44% (P =.25), respectively (Fig. 2). TRM of RIST trended to be low compared with that of CST (18% vs 22%, P =.87). In addition, chronic GVHD was observed in 91% of the evaluable 11 pts (limited type, 6; extensive type, 5). It is suggested that both improvement of TRM and the induction of graft-versus-leukemia effects may contribute to the favorable outcome in RIST for ATL. Furthermore, it should be stressed that older pts who preferentially received RIST rather than CST achieved favorable survival comparable to younger pts (≥ 50 years: 58% vs < 50 years: 60%, P =.94). We would suggest that RIST should be applied to all ATL pts eligible for allo-SCT, regardless of the age. Univariate analysis for all pts revealed that only male sexuality was a significant poor prognostic factor for OS (male: 25% vs female: 82%, P =.006). Regarding disease status at SCT, CR or non-CR did not significantly affect OS (CR: 67% vs non-CR: 58%, P =.98). However, PD was an adverse impact on 3-year OS (PD: 33% vs non-PD: 64%, P =.11). It is recommended that ATL pts receive allo-SCT in early phase before the disease becomes chemo-resistant, even if they do not achieve CR. Conclusion: Allo-SCT for ATL remarkably improved the poor prognosis. Especially, RIST is a promising procedure for excellent outcome. Disclosures: No relevant conflicts of interest to declare.

Outcome Of Patients With HTLV-1 Associated Adult T-Cell Leukemia/Lymphoma (ATL) Who Have Undergone Stem Cell Transplantation: A Retrospective Study Of The EBMT Lymphoma Working Party

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3398-3398
Author(s):  
Ali Bazarbachi ◽  
Kate Cwynarski ◽  
Ariane Boumendil ◽  
Herve Finel ◽  
Paul Fields ◽  
...  
Keyword(s):  
Stem Cell ◽  
Retrospective Study ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
Reduced Intensity

Abstract Introduction Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy of mature activated T-cells caused by the human T cell lymphotropic virus type I (HTLV-1). ATL carries a very poor prognosis because of intrinsic chemoresistance and severe immunosuppression. Indeed, prognosis of the two most frequent forms of the disease (acute ATL and ATL lymphoma) remains dismal with a median survival of less than 12 months. A recent worldwide metaanalysis demonstrated that the combination of zidovudine and interferon-alpha is highly effective in the chronic and acute subtypes of ATL and should be considered as standard first line therapy in that setting. However, because of the high rate of relapse in acute subtype and lymphoma, allogeneic stem cell transplantation (allo-SCT) is an attractive potentially curative option. A number of retrospective studies from Japan confirmed the feasibility of myeloablative or reduced-intensity conditioning allo-SCT in ATL patients and a large retrospective study reported a 3-year overall survival of 33%. No reports on allo-SCT are available outside Japan. Study design We performed a retrospective analysis of transplanted ATL patients in the EBMT registry. Results Data could be retrieved for 21 HTLV-I seropositive patients transplanted between 2004 and 2010 for ATL (10 males, 11 females; median age 48 years; range 21-67; interquartile range 36-52). According to the Shimoyama classification, 7 (33%) patients had acute ATL, 12 (57%) had ATL lymphoma and 2 (9%) had an unknown subtype. At transplant, 12 (57%) patients were in complete remission, 5 (24%) patients were in partial remission and 4 (19%) patients were refractory. Four (19%) patients received autologous SCT (auto-SCT), all of whom died from relapsed/refractory disease in less than one year. Seventeen patients (81%) received allo-SCT (4 myeloablative, 13 reduced intensity and one unknown conditioning) from identical sibling (6), haploidentical relative (3), unrelated (7) or unknown donor (1). Of those who underwent allo-SCT 6/17 patients are alive and the majority of them (4/6) were in CR at time of allo-SCT. Eleven patients died (65%) within 2 years of allo-SCT (median time to death was 5 months), 8 of relapse/progression and 3 from transplant related causes (sepsis n=1; GVHD n=2.) Four patients developed acute GVHD (24%). Data on chronic GVHD were available for 15 patients. Eight patients developed chronic GVHD, 4 were alive at last FU, 2 died from relapse/progression and 2 died from GVHD. Conversely, seven patients did not develop chronic GVHD, 5 of them died from relapse/progression. Conclusion Overall these results indicate that allo-SCT but not auto-SCT may salvage a subset of ATL patients, particularly those transplanted in CR and who achieve chronic GVHD suggesting the existence of graft versus ATL effect. Although based on a low number of patients these data are consistent with those previously reported by Japanese studies. Disclosures: Dreger: Riemser Pharma : Consultancy, Honoraria, Research Funding.

scholarly journals Association between preconditioning absolute lymphocyte count and transplant outcomes in patients undergoing matched unrelated donor allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning and anti-thymocyte globulin

2021 ◽  
Vol 12 ◽  
pp. 204062072110637
Author(s):  
Jeongmin Seo ◽  
Dong-Yeop Shin ◽  
Youngil Koh ◽  
Inho Kim ◽  
Sung-Soo Yoon ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cell Depletion ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Matched Unrelated Donor ◽  
T Cell Depletion ◽  
Reduced Intensity

Background: Allogeneic stem cell transplantation (alloSCT) offers cure chance for various hematologic malignancies, but graft- versus-host disease (GVHD) remains a major impediment. Anti-thymocyte globulin (ATG) is used for prophylactic T-cell depletion and GVHD prevention, but there are no clear guidelines for the optimal dosing of ATG. It is suspected that for patients with low absolute lymphocyte counts (ALCs), current weight-based dosing of ATG can be excessive, which can result in profound T-cell depletion and poor transplant outcome. Methods: The objective of the study is to evaluate the association of low preconditioning ALC with outcomes in patients undergoing matched unrelated donor (MUD) alloSCT with reduced-intensity conditioning (RIC) and ATG. We conducted a single-center retrospective longitudinal cohort study of acute leukemia and myelodysplastic syndrome patients over 18 years old undergoing alloSCT. In total, 64 patients were included and dichotomized into lower ALC and higher ALC groups with the cutoff of 500/μl on D-7. Results: Patients with preconditioning ALC <500/μl were associated with shorter overall survival (OS) and higher infectious mortality. The incidence of acute GVHD and moderate-severe chronic GVHD as well as relapse rates did not differ according to preconditioning ALC. In multivariate analyses, low preconditioning ALC was recognized as an independent adverse prognostic factor for OS. Conclusion: Patients with lower ALC are exposed to excessive dose of ATG, leading to profound T-cell depletion that results in higher infectious mortality and shorter OS. Our results call for the implementation of more creative dosing regimens for patients with low preconditioning ALC.

Bortezomib, Doxorubicin, Cyclophosphamide, Dexamethasone Induction Followed by Stem Cell Transplantation for Primary Plasma Cell Leukemia: A Prospective Phase II Study of the Intergroupe Francophone du Myélome

2016 ◽  
Vol 34 (18) ◽  
pp. 2125-2132 ◽  
Author(s):  
Bruno Royer ◽  
Stéphane Minvielle ◽  
Momar Diouf ◽  
Murielle Roussel ◽  
Lionel Karlin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Plasma Cell ◽  
Phase Ii ◽  
Cell Leukemia ◽  
Reduced Intensity Conditioning ◽  
Prospective Phase ◽  
Primary Plasma Cell Leukemia ◽  
Reduced Intensity

Purpose Primary plasma cell leukemia (pPCL) is a rare and aggressive malignancy with a poor prognosis. With conventional chemotherapy, patients typically die within 1 year. In all but one of the retrospective studies reported to date, bortezomib and lenalidomide seem to improve survival. We conducted a prospective phase II trial in patients with pPCL to assess the efficacy of an alternate regimen that combines standard chemotherapy, a proteasome inhibitor, and high-dose melphalan and autologous stem cell transplantation (HDM/ASCT) followed by either allogeneic transplantation or bortezomib/lenalidomide maintenance. Patients and Methods Patients 70 years old and younger with newly diagnosed pPCL received four alternating cycles of bortezomib, dexamethasone plus doxorubicin or cyclophosphamide. Peripheral blood stem cells were collected from responding patients with < 1% of circulating plasma cells before HDM/ASCT. As consolidation, young patients received a reduced-intensity conditioning allograft, whereas the remaining patients underwent a second HDM/ASCT followed by 1 year of bortezomib, lenalidomide, dexamethasone. The primary end point was progression-free survival (PFS). Results Forty patients (median age, 57 years; range, 27 to 71 years) were enrolled. The median follow-up was 28.7 months. In the intention-to-treat analysis, the median PFS and overall survival were 15.1 (95% CI, 8.4; -) and 36.3 (95% CI, 25.6; -) months, respectively. The overall response rate to induction was 69%. One patient underwent a syngeneic allograft and 25 HDM/ASCT (16 of whom subsequently received a reduced-intensity conditioning allograft and seven a second ASCT followed by maintenance). Conclusion In this prospective trial in patients with pPCL, we show that bortezomib, dexamethasone plus doxorubicin or cyclophosphamide induction followed by transplantation induces high response rates and appears to significantly improve PFS.

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