Long-Term Outcome of ATL Patients Who Underwent Reduced-Intensity Stem Cell Transplantation (RIST): Suggested Potent Graft-Versus-ATL and HTLV-1 Effects.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3370-3370
Author(s):  
Ryuji Tanosaki ◽  
Kimikazu Yakushijin ◽  
Yoshitaka Asakura ◽  
Saiko Kurosawa ◽  
Nobuhiro Hiramoto ◽  
...  
Keyword(s):  
Stem Cell ◽  
Surgical Resection ◽  
Proviral Load ◽  
Single Site ◽  
Acute Type ◽  
Long Term Outcome ◽  
Immunological Mechanism ◽  
Clinical Responses ◽  
Related Donor

Abstract Abstract 3370 Poster Board III-258 Although the outcome of patients (pts) with adult T-cell leukemia-lymphoma (ATL) remains poor when they are treated with conventional chemotherapy, we previously showed in a multi-center prospective study that one-third of pts who underwent RIST from a related donor in CR or PR could survive without disease for more than 2 years (Tanosaki R et al., BBMT 2008). In this retrospective study, we reviewed our single-center experience with RIST for ATL pts, focusing on the outcome of those who underwent RIST in non-remission status or who relapsed after RIST. A total of 24 pts underwent RIST from a related donor between 2001 and 2008. The median age was 54 years (range, 44-65). Of the 14 males and 10 females, 19 were acute type and 5 were lymphoma type. Disease status at transplantation was 5 CR, 10 PR, 8 NC and 1 PD. Donors were siblings in 18 and children in 6, including 5 HTLV-1 healthy carriers. HLA in serology was 6/6 in 19 and 5/6 in 5. Stem cell sources were PBSC in 22 and BM in 2. Conditioning regimens were fludarabine (30 mg/m2 iv days -8 to -3) and busulfan (3.2 mg/kg iv days -6 and -5) with (n=8) or without (n=16) rabbit anti-T-lymphocyte globulin (ATG, Fresenius; 2.5 mg/kg iv days -2 and -1). All patients received cyclosporine alone for GVHD prophylaxis. Engraftment was rapid in all 24 pts (neutrophil>500/uL; median 12 days, range 10 -19), with no graft failure. There were 3 non-relapse mortalities; respiratory failure from bronchiolitis obliterans at 21 months (mos), interstitial pneumonitis at 47 mos, and pneumococcal sepsis at 38 mos. Notably, 10 of the 19 pts who were non-CR at RIST survived without disease progression to a median of 53 mos (range, 20 to 85). All of these pts were acute type, and had circulating ATL cells in the peripheral blood (PB) immediately before RIST (average 33% of WBC, range 5-73). Circulating ATL cells decreased to below 5% within 1 mo in 8 pts. A total of 12 pts relapsed within 16 mos; 7 (58%) within 3 mos, and 11 (92%) within 12 mos. Two patients who had relapsed after RIST showed a significant but transient response to the withdrawal of immunosuppression (CR 1, PR 1). Donor lymphocyte infusion was performed in 6 pts without significant benefits. Seven pts who relapsed at a single site, which was confirmed by CT scan or FDG-PET, were treated with local irradiation alone, and 3 whose HTLV-1 proviral load in PB had become negative at relapse survived to 48, 64 and 77 mos; 1 pt required 2 courses of irradiation because of immediate relapse at the margin of the preceding radiation field, and another pt underwent surgical resection of a residual mass since a biopsy revealed a viable lesion at the irradiated site. The 5-year overall and progression-free survival of all pts were 52% (95% CI, 38-66%) and 37% (95% CI, 22-52%), respectively, at a median follow-up of 59 mos (range, 12 to 85) in surviving pts. HTLV-1 proviral load in PB was examined using real-time PCR for tax in 208 samples from 21 evaluable pts, and it became negative at least once in 15 pts (71%), including 1 pt whose donor was an HTVL-1 carrier; proviral load remained negative in 7 pts at a median follow-up of 32 mos (range, 3 to 84). Since HTLV-1 tax is a promising target molecule for identifying the immunological mechanism, HLA-restricted tax-specific CTLs were examined in HLA-A2- and/or A24-positive pts using tax tetramers by taking blood samples periodically after informed consent was obtained from each pt. A total of 80 samples in 13 pts were analyzed. The number of tax tetramer-positive (tax+) cells did not change significantly up to at least 1 year after RIST, while the clinical responses and decrease/disappearance of HTLV-1 proviral load were observed within 3 mos in most cases. An increase in tax+ cells was observed after 1 year in 2 pts who had achieved CR. In conclusion, about half of the acute-type ATL pts with a significant involvement of ATL cells in PB at RIST could survive for a long time in our cohort. ATL pts who relapsed at a single site after RIST still have a chance to be cured with local treatment using irradiation alone or surgical resection with the aid of HTLV-1 proviral load as a marker for minimum residual disease. Since most ATL pts had already become resistant to chemotherapy and the intensity of conditioning was reduced, potent GV-ATL and GV-HTLV-1 effects might have played a key role in disease control. However, tax-specific CTL kinetics did not correlate with either clinical responses or the HTLV-1 proviral load, which suggested that other molecules may be immunologically targeted. Our results might contribute to the establishment of the cure-oriented treatment strategy for ATL pts. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Long-Term Outcome of Allogeneic Stem Cell Transplantation in Patients with Paroxysmal Nocturnal Hemoglobinuria with or without Aplastic Anemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2195-2195
Author(s):  
Sung-Eun Lee ◽  
Sung Soo Park ◽  
Young-Woo Jeon ◽  
Jae-Ho Yoon ◽  
Byung Sik Cho ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Acute Gvhd ◽  
Conditioning Regimen ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Pnh Clone

Abstract Background: Although recently, Eculizumab, humanized monoclonal antibody directed against complement component C5, has used increasingly for the patients with hemolytic paroxysmal nocturnal hemoglobinuria (PNH), allogeneic stem cell transplantation (allo-SCT) can be curative treatment option especially for PNH patients with combined aplastic anemia (AA). The aim of the present study was to evaluate long-term outcome of allo-SCT in patients with AA/PNH. In addition, patients with classic PNH who underwent allo-SCT in the pre-eculizumab era were also evaluated. Methods: Total of 33 patients with PNH clones underwent allogeneic SCT at our institution between Jan 1998 and Jan 2016. Among them, seven patients had classic PNH and 26 patients with cytopenia had AA/PNH (with bone marrow evidence of a concomitant AA). Results: There were 21 male and 12 female patients with a median age of 34 years (range, 13-56 years). Pre-transplant GPI-AP deficient neutrophils and erythrocytes were 5.6% (0-92) and 21% (0-98.5), respectively. Median white blood cell, absolute neutrophil count, hemoglobin, and platelet at transplant were 2.4×109/L, 0.8×109/L, 7.7 g/dL, and 27×109/L, respectively. Median LDH level was 727 U/L (232-7721 U/L) and 19 (58%) patients had LDH ≥1.5x upper limit of normal. Classic PNH (n=7) and AA/PNH [SAA (n=15), VSAA (n=9), or non-SAA (n=2)] received SCT from HLA-matched sibling (MSD, n=24), unrelated (URD, n=7), or haplo-identical donor (Haplo-SCT, n=2). Since 2003, the conditioning regimen for MSD-SCT was changed from Busulfex (12.8 mg/kg) + cyclophosphamide (CY, 120 mg/kg) to fludarabine (180 mg/m2) + CY (100 mg/kg) + rATG (10 mg/kg). The conditioning regimen for URD-SCT and Haplo-SCT were TBI (800 cGy) + CY (100-120 mg/kg) ± rATG (2.5 mg/kg) and TBI 600cGy + Fludarabine (150 mg/m2) + rATG (5 mg/kg), respectively. After a median follow-up of 57 months (range 6.0-151.3), the 5-year estimated OS rates were 87.9 ± 5.7%. Four patients died of treatment-related mortality (TRM), including acute GVHD (n=1), pneumonia (n = 2), and cerebral hemorrhage (n=1), respectively. Except one patient with early TRM, 32 patients engrafted. Two patients who experienced delayed graft-failure received second transplant and recovered. The cumulative incidence of acute GVHD (≥grade II) and chronic GVHD was 27.3 ± 7.9% and 18.7 ± 7.0%, respectively. Among 25 patients with available follow-up data, PNH clone disappeared at median 3.0 months (range 0.7-45.5) after SCT and reemerging of PNH clones was observed in two patients; one patient showed re-appearance of 2.6% GPI-negative neutrophils at 12 months without PNH symptoms, but disappeared again at 21 months. Another patient suffered from labile graft and received a booster with peripheral blood stem cells. Conclusion: This study showed that long-term transplant outcome in patients with AA/PNH were comparable to that of allogeneic SCT in SAA (the 3-year estimated OS rates were 92.7 and 89 % for MSD-SCT and URD-SCT, respectively) at our institution (ASH Annual Meeting Abstracts 2012;120:4151). Reduced-intensity conditioning regimen was sufficient for the eradication of PNH clone in allogeneic SCT. Therefore, application of allogeneic SCT should be considered in PNH patients with AA in case of availability of well matched donor. Disclosures No relevant conflicts of interest to declare.

CHOP Plus Rituximab (CHOP-R) in Waldenström’s Macroglobulinemia (WM).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4930-4930 ◽  
Author(s):  
Zachary Hunter ◽  
Andrew Branagan ◽  
Steven Treon
Keyword(s):  
Stem Cell ◽  
Effector Cell ◽  
Standard Dose ◽  
Autologous Transplantation ◽  
Low Grade ◽  
First Line ◽  
Consensus Panel ◽  
Highly Active ◽  
Clinical Responses

Abstract Recently, a consensus panel of experts recommended alkylator therapy, nucleoside analogues and rituximab as appropriate first line therapies for WM (Semin Oncol2003; 30:121). It was also recommended that candidates for future autologous transplantation should have limited alkylator or nucleoside analogue exposure due to potential stem cell harm. CHOP-R (cyclophosphamide, adriamycin, vincristine, prednisone, rituximab) is a highly active, stem cell sparing regimen that has been extensively evaluated in other low-grade Non-Hodgkin’s lymphoma patients. No published experience in WM exists. As such, we analyzed the outcome of 13 patients with WM who received CHOP-R at our Institution. Patients had a median age of 54 (range 44–72) yrs, and a median of 1 (range 0–5) prior therapies. 8 of 13 (62%) patients had relapsed (n=2) or were refractory (n=6) to fludarabine. Five patients had received rituximab previously. Patients received a median of 6 cycles (range 2–6) of standard dose CHOP, and 6 infusions (range 2–6) of Rituximab (375 mg/m2). Three patients received additional rituximab (4 weekly infusions every 6 months) as maintenance therapy. Median IgM for all patients declined from 4,975 (range 1,960–12,400) to 1,575 (range 62–8,230) mg/dL (p=7 x 10−5); median S.V. 2.8 (range 1.5–12) declined to 1.6 (range 1.3–4.8) CP (p=0.04). Importantly, the median hematocrit rose from 30.7 (range 21.9–35.6) to 39 (range 24.3–43.2) p=0.005. Clinical responses were as follows: 3 CR/CRu; 7 PR; 2 MR. One patient is in stable disease after 3 cycles of CHOP-R. With a median follow-up of 8 (range 3–28) months, no patient has progressed. Therapy was well tolerated for most patients. Two patients had febrile neutropenia with documented bacteremia and recovered without any complication. Circulating effector cell levels pre- and post-CHOP-R were also evaluated in 6 patients since rituximab activity is mediated in part by ADCC activity. No significant change in CD3+, CD4+, CD8+, and CD16+/CD56+ effector cell levels occurred following CHOP-R as assessed by multicolor flow cytometry.

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 ◽  
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

Surgical resection of pulmonary inflammatory pseudotumors: long-term outcome

2017 ◽  
Vol 25 (6) ◽  
pp. 440-445 ◽  
Author(s):  
Marine Peretti ◽  
Dana M Radu ◽  
Karel Pfeuty ◽  
Antoine Dujon ◽  
Marc Riquet ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Survival Rates ◽  
R0 Resection ◽  
Term Outcome ◽  
Term Survival ◽  
Long Term Outcome ◽  
Long Term Survival ◽  
Inflammatory Pseudotumors

Background Pulmonary inflammatory pseudotumors are rare lesions that remain problematic in several aspects, especially regarding the therapeutic strategy. The goal of this study was to evaluate long-term survival in a multicenter series of patients who required surgery for pulmonary inflammatory pseudotumors. Methods Thirty-six cases of pulmonary inflammatory pseudotumors, operated on in 3 French thoracic surgery departments between 1989 and 2015, were studied retrospectively. We recorded pre-, peri- and postoperative data for each patient, and long-term survival was analyzed. Results There were 22 men and 14 women. Mean age was 53.5 years (range 14–81 years). Three pneumonectomies, 1 bilobectomy, 19 lobectomies, 2 segmentectomies, 10 wedge resections, and 1 biopsy were performed. Complete resection was carried out in 32 (88.8%) patients. Median follow-up was 76 months. Five-year and 10-year survival rates were respectively 86.8% and 81.7% (96% and 90% for patients with R0 resection). Conclusions Long-term survival was excellent for patients with pulmonary inflammatory pseudotumors who benefited from surgery, especially when surgical resection was complete. These results confirm that surgical resection must be proposed as the first-line treatment for patients with pulmonary inflammatory pseudotumors.

Long-Term Outcome of Allogeneic Stem Cell Transplantation (allo-SCT) in Patients with Waldenstrom Macroglobulinemia (WM)-a Retrospective Study of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4661-4661 ◽  
Author(s):  
Charalampia Kyriakou ◽  
Ariane Boumendil ◽  
Herve Finel ◽  
Norbert Schmitz ◽  
Henrik Sengeloev ◽  
...  
Keyword(s):  
Stem Cell ◽  
Retrospective Study ◽  
Treatment Algorithm ◽  
Disease Status ◽  
Line Treatment ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Reduced Intensity

Abstract WM is an indolent lymphoma that has benefited from the introduction of novel agents with the achievement of higher response rates. However, WM remains incurable with conventional treatment. In addition, patients with high risk disease have either transient short lived responses or are refractory to conventional treatments. Although international treatment recommendations suggest considering allo-SCT in late relapses or in refractory younger patients, the place and timing of allo-SCT in the treatment algorithm of WM remains unclear. The aim of the present study was to analyse the long-term outcome of allo-SCT in WM. Patients and methods: Eligible for this retrospective study were patients aged 18 years or older who had a first reduced intensity (RIC) or myeloablative (MAC) conditioning allo-SCT (10/10 matched donor, sibling or unrelated) for WM between 2001 and 2013 and were registered with the EBMT. Baseline patient, disease and transplant data were collected from MED-A forms. Centers were requested to provide additional diagnostic, treatment and follow-up information. Statistical analysis used log rank test to assess the impact of baseline characteristics on survival endpoints. In multivariate analysis, prognostic factors for survival were estimated using Cox regression models and for relapse incidence (IR) and non-relapse mortality (NRM) by Fine and Gray models. Results: 260 patients (72% male) fulfilling the inclusion criteria of this study were identified in the database. The median age was 52 (range 19-72) years. Disease status at allo-SCT was sensitive in 78% and refractory in 22% of the patients. Conditioning was reduced-intensity (RIC) in 66%, with PBSC (92%) being the predominant stem cell source (bone marrow 7%, cord blood 1%). Patients receiving RIC were significantly older and had a longer interval between diagnosis and transplant but were otherwise comparable to patients with myeloablative conditioning (MAC). Donors were related in 65% and unrelated in 35% of the transplants. The median number of treatment lines prior to alloSCT was 3. Pretreatment details were available for 118 patients. Of these, first-line treatment was alkylator-based in 80%, purine analogue (PA)-based in 17%, and contained rituximab in 23%; for 2nd-line treatment, these figures were 50%, 36%, and 34%; and for 3rd-line treatment 41%, 32%, and 44%. Less than 10% of the patients had received bortezomib or imide-based regimens in any pretreatment line. At 100 days the cumulative incidence of acute graft versus host disease (aGVHD) grade I-II was 35%, and grade III-IV was 12%. At 2 years the cumulative incidence of chronic GVHD (cGVHD) was 41%. The development of cGVHD did not significantly impact on any outcome on a landmark analysis. After a median follow-up for living patients of 57 months (IQR 31-97), 5-year NRM, IR, progression-free survival (PFS) and overall survival (OS) were 29%, 24%, 47% and 55%. Risk factor analyses considering age, sex, performance status (PS), disease status, pretreatment lines, rituximab exposure, year of transplant, donor, and conditioning identified PS for NRM, disease status for IR, and PS and MAC for OS as significant predictors of an adverse outcome after multivariable adjustment. Although RIC patients tended to have a lower NRM and a better PFS than MAC patients, this was not statistically significant, suggesting that RIC patients had a better survival after relapse. 45 patients were treated with donor lymphocyte infusions (DLI) and results of DLI were reported in 22 patients. Of these, a response was observed in 60%, which was complete in 55%. Conclusions: This large study demonstrates that allo-SCT can effectively induce long-term disease control in heavily pre-treated patients with WM, suggesting that graft-versus-lymphoma effects are active and stable in WM. Accordingly, DLI seems to be a promising treatment option in case of post-transplant disease recurrence. Additional studies are needed to elaborate the place of allo-SCT in the treatment algorithm of WM in the era of novel agents. Disclosures No relevant conflicts of interest to declare.

scholarly journals RARE-09. PRESERVATION OF ENDOCRINE FUNCTION AFTER OMMAYA RESERVOIR INSERTION IN CHILDREN WITH CYSTIC CRANIOPHARYNGIOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii443-iii443
Author(s):  
Laura-Nanna Lohkamp ◽  
Abhaya Kulkarni ◽  
James Drake ◽  
James T Rutka ◽  
Peter Dirks ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Invasive Procedure ◽  
Retrospective Chart Review ◽  
Ommaya Reservoir ◽  
Endocrine Function ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Sick Children

Abstract INTRODUCTION Children with craniopharyngiomas (CP) can be subjected to significant morbidities caused by radical surgery and/or radiation with severe long-term consequences. Ommaya reservoir Insertion (ORI) into cystic CP represents a minimally invasive procedure that aims to preserve endocrine, hypothalamic and neurocognitive function. The purpose of this study was to determine the relevance of upfront ORI (+/- intracystic treatment) for preservation of endocrine function. METHODS A retrospective chart review of children with CP treated at the Hospital for Sick Children between 01/01/2000 and 15/01/2020 was undertaken. Endocrine function was reviewed at the time of initial ORI or surgical resection and throughout the course of follow-up. Event free survival (EFS) was defined as the time to additional surgical resection or irradiation. RESULTS Fifty-five patients with sufficient endocrine follow-up data were included. The median age of diagnosis was 8.3 years (range 2.1–18.0 years), 31 were males. ORI was performed as upfront treatment in 30 patients, gross total or partial resection in 24 patients and radiation in 1 patient, respectively. Endocrine function remained stable after ORI with a median EFS of 19.2 (0 – 105.3) months while the majority of patients who underwent surgical resection had documented worsened endocrine function postoperatively (median of 0; range 0 – 29.4 months) (p< 0.001). The event most commonly related to secondary endocrine deterioration was initial or delayed surgical resection. CONCLUSIONS Endocrine function was preserved in patients with upfront ORI (+/- intracystic treatment). Further studies will elucidate the implications of ORI with respect to ophthalmological, vascular and neurocognitive long-term outcome.

scholarly journals Long-Term Outcome of Reduced Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Mycosis Fungoides and Sézary Syndrome: The Milan Experience

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4655-4655
Author(s):  
Francesco Onida ◽  
Giorgia Saporiti ◽  
Silvia Alberti Violetti ◽  
Elena Tagliaferri ◽  
Federica Grifoni ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Median Time ◽  
Term Outcome ◽  
Hematopoietic Stem ◽  
Long Term Outcome ◽  
Reduced Intensity

Abstract Introduction: Although a few novel drugs have recently shown promising activity in mycosis fungoides (MF) and Sézary syndrome (SS), prognosis of patients with advanced stages or refractory disease remain poor, with median survival ranging from 1.4 to 3.4 years (Agar NS et al. JCO 2010). In selected patients, allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents a potential curative strategy. By decreasing transplant-related mortality, reduced intensity (RIC) and nonmyeloablative conditioning (NMA) regimens lead to better outcomes in comparison to myeloablative ones. Here we report long-term outcome of our RIC allo-HSCT experimental program, initiated in 2001. Patients & Methods: As of July 2018, in our Center 40 patients underwent RIC allo-HSCT from HLA-identical sibling (n=16), unrelated donors (UD, n=22 - fully-matched in 10, 1 or 2-mismatch in 12) or haploidentical related donors (n=2). Median age was 52 years (range 19-66). All patients (24 M and 16 F) had stage IIB/IV refractory MF (n=27) or SS (n=13). Median number of previous treatment lines was 6 (range 2-12) while median time from diagnosis to transplantation was 46 months (range 11-264). The source of stem cells has been peripheral blood in 35 patients (87.5%), bone marrow in 4 (10%) and cord blood in 1 (2.5%). Conditioning regimens included FC/TBI200, pentostatin+TBI200, and fludarabine/melphalan in transplants from HLA-identical sibling donor or UD, whereas the TT/Flu/CTX/TBI200 regimen was used in the haploidentical setting. GvHD prophylaxis included CsA/MMF in all patients, with the addition of ATG in cases with UD and post-transplant CTX (50 mg/kg giorni +3 e +4) in haploidentical setting. Results: Full donor chimerism was obtained in 32 out of 37 evaluable patients, in a median time of 2 months (range 1-12). Acute GvHD occurred in 18 patients out of the 32 evaluable (56%), being of grade III-IV in 9 (28%). Chronic GvHD was observed in 10 patients (31%), being extensive in 4 (12%). Of note, the latter were all patients transplanted from HLA-identical sibling (i.e. without ATG). Following transplantation, a complete remission (CR) was achieved in 26 out of the 37 evaluable patients (70%), of whom 4 experienced relapse at +2 (2 pts), +25 and +35 months, respectively. At the last follow-up, 19 patients were alive and 17 (89%) maintained CR after a median follow-up of 80 months (range 4-210). Out of the 11 patients who did not achieve CR, 9 died from progressive disease (median follow-up of 12 months, range 3-31), 1 from a secondary malignancy, while 1 is still alive with disease 62 months after transplant. Transplant-related death occurred in 7 patients (17%), of whom 5 were in CR. In the whole population, the 5-year OS was 52% (95% CI 34-70) [Fig.1] and the 5-year DFS was 43% (95% CI 27-62). However, when MF and SS were analysed separately, 5-yrs DFS were 30% (95% CI 12-51) and 72% (95% CI 38-99), respectively (Fig.2). Apart from diagnosis, outcome appeared to be primarily associated with chemosensitivity and status of disease at transplantation. Conclusions: After a median follow-up longer than 6.5 years, we confirm the efficacy of RIC allo-HSCT as a powerful therapeutic strategy in inducing and maintaining remission in selected patients with chemosensitive advanced-stage CTCL, with results particularly encouraging in SS. Disclosures Cortelezzi: roche: Consultancy; abbvie: Consultancy; novartis: Consultancy; janssen: Consultancy.

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