Encouraging Results of Reduced Intensity Conditioning (RIC) Umbilical Cord Blood (UCB) Transplantation for the Treatment of Advanced Lymphoid Malignancies.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2028-2028
Author(s):  
Claudio G. Brunstein ◽  
Susana Cantero ◽  
Qing Cao ◽  
Navneet Majhail ◽  
Brian McClune ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Cell Lymphoma ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Large Cell ◽  
Lymphocytic Leukemia ◽  
Promising Alternative ◽  
Lymphoid Malignancies ◽  
Significant Difference

Abstract We have reported on the safety and efficacy of RIC UCB transplantation for patients with advanced hematologic diseases. Here we report on 65 patients, median age of 46 yrs (range, 6–68), who underwent RIC UCB transplantation for the treatment of advanced lymphoid malignancies between October 2001 and December 2006. Patients received either one (n=9) or two (n=56) UCB unit grafts matched at 4–6/6 HLA loci. Forty were male and 27 CMV seropositive. Diagnoses were follicular lymphoma (FL, n=11), small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL, n=9), mantle cell lymphoma (MCL, n=8), large cell lymphoma (LCL, n=14), and Hodgkin’s lymphoma (HL, n=23). Conditioning regimen was cyclophosphamide 50 mg/kg (Day-6), fludarabine 40mg/m2 for 5 days (Day-6 to -2), and single fraction total body irradiation of 200cGy (Day -1), plus cyclosporine A and mycophenolate mofetil (to day +30). At transplantation 53 patients (81%) had chemotherapy sensitive disease, 5 (8%) had bulky adenopathy (≥ 5 cm), 27 (42%) had prior radiation therapy, 26 (40%) had prior autologous transplant, 22 (34%) had an elevated LDH, and 10 (15%) had marrow involvement. The median number of prior treatment courses was 4 (range, 1–9). The median follow-up for survivors is 23 mos. (range, 4–62). Patients were analyzed as indolent (IND=FL+ SLL/CLL), aggressive (AGR=LCL+MCL), and HL. Incidence of acute GVHD grades II–IV was 57% (95%CI, 43–70); grades III–IV 25% (95%CI, 14–35); chronic GVHD 23% (95%CI, 11–35), with similar incidence of acute and chronic GVHD between lymphoma subgroups. The 3-year nonrelapse mortality (NRM) was 15% (95%CI, 5–26) with no significant difference among lymphoma subgroups (IND 5% vs. AGR 24% vs. HL 13%, p=.41). Thirty-five patients (53%) had relapsed or progressive disease with a 3-year progression-free survival (PFS) of 31% (95%CI, 19–44); IND 44% (95%CI, 22–66); AGR 20% (95%CI, 2–39); HL 35% (95%CI, 15–54) (p=.30). Fourteen of these 35 patients were treated with tapering of immunosuppression and rituximab and/or chemotherapy or radiation therapy, and 8 achieved a complete remission. Three-year OS was 55% (95%CI, 42–68); IND 69% (95%CI, 48–90); AGR 54% (95%CI, 33–75); HL 43% (95%CI, 18–69) (p=.37). We conclude that RIC UCB is effective alternative for the treatment of patients with advanced lymphoid malignancy resulting in acceptable NRM and encouraging OS and PFS. Patients with advanced lymphoid malignancies should be considered for a RIC UCBT as a promising alternative for those with no available sibling donor.

Umbilical Cord Blood (UCB) Transplantation after Non-Myeloablative (NMA) Conditioning for Advanced Follicular Lymphoma, Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia: Low Transplant-Related Mortality and High Progression-Free Survival.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2900-2900 ◽  
Author(s):  
Juliet N. Barker ◽  
Daniel J. Weisdorf ◽  
Todd E. DeFor ◽  
Claudio G. Brunstein ◽  
John E. Wagner
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cumulative Incidence ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Free Survival ◽  
Lymphoid Malignancies ◽  
Mantle Cell ◽  
Related Mortality

Abstract A graft-versus-leukemia/lymphoma (GVL) effect after allografting has been documented for advanced or refractory indolent B cell Non-Hodgkin’s lymphoma (NHL), mantle cell lymphoma (MCL), and chronic lymphocytic leukemia (CLL). However, widespread application of allografting in these patients has been limited by lack of suitable donors as well as high transplant-related mortality (TRM) when conventional myeloablative conditioning is used. NMA conditioning is associated with reduced TRM and has been successful in patients with these B cell lymphoid malignancies transplanted with HLA-matched sibling donors. Therefore, to extend access to transplant, we evaluated the effectiveness of NMA conditioning followed by unrelated donor UCB transplantation (UCBT) in patients with these diseases. Patients received 50 mg/kg cyclophosphamide, 200 mg/m2 fludarabine and 200 cGy TBI with cyclosporine and mycophenolate mofetil immunosuppression. Sixteen patients with advanced or refractory follicular NHL (n=7), MCL (n=3), or CLL (n=6) were transplanted between 10/3/2001 and 11/30/2004. Median patient age was 51 years (range, 37–67) and weight was 81 kg (range, 60–102). Patients received single (n=4) or double unit (n=12) 4–6/6 HLA-matched (intermediate resolution DNA typing at HLA-A and B; high resolution HLA-DRB1) UCB grafts with a median infused cell dose of 3.5 x 107 NC/kg (range, 2.6–4.6) and 5.0 x 107 CD34+ cells/kg (range, 2.6–14.3). Cumulative incidence of sustained donor engraftment was 81% (95%CI: 62–100) with a median day of neutrophil recovery of 8 days (range, 5–30). Two of the 3 patients with failure of donor engraftment had received only a single cycle of CVP chemotherapy immediately prior to UCBT. Twelve patients had grade 2–4 acute graft-versus-host disease (GVHD) (9 grade 2, 2 grade 3, and 1 grade 4) for a cumulative incidence of 75% (95%CI: 49–100) by day 100, while 6 patients had extensive chronic GVHD for a cumulative incidence of 39% (95%CI: 14–64) by 1 year. The cumulative incidence of TRM at 6 months was 6% (95%CI: 0–17). At a median follow-up of 22 months (range 7–42), 4 patients (3 follicular NHL, 1 CLL) have died (3 with progressive disease and 1 with infection) whereas 12 are alive in complete remission with a probability of progression-free survival of 63% (95%CI: 49–87) at 1 year. Two follicular NHL patients, both refractory to rituximab pre-transplant, required the addition of rituximab post-transplant to achieve sustained remission. Also, 2 of 3 patients (both with CLL) who had transient donor engraftment but subsequent autologous recovery are in remission at 14 and 15 months after UCBT, respectively. In conclusion, these preliminary results suggest that UCBT after NMA conditioning is an effective treatment for B cell lymphoid malignancies in adults with a low rate of TRM. Based on these data, and data in other patients undergoing NMA transplantation, therapy immediately prior to UCBT is likely an important factor in donor engraftment. A GVL effect is suggested and may be augmented by the addition of rituximab. This strategy extends treatment options for patients with advanced or refractory follicular NHL, mantle cell NHL, and CLL who are otherwise fit and warrants further investigation. Finally, given the low TRM, patient referral prior to the development of refractory disease should be strongly considered and may further improve outcomes.

Allogeneic Stem Cell Transplantation (Allo-SCT) in the Management of Advanced Waldenstrom’s Macroglobulinemia (WM).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 619-619
Author(s):  
Charalampia Kyriakou ◽  
C. Canals ◽  
A. Sureda ◽  
G. Taghipour ◽  
J. Cornelissen ◽  
...  
Keyword(s):  
Median Time ◽  
Relapse Rate ◽  
Residual Disease ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Mixed Chimerism ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Significant Difference

Abstract Despite effectiveness of standard chemotherapy regimens, complete response is infrequent in WM patients and there is no cure. The role of Allo-SCT has not been extensively explored and the available data are limited. In this retrospective European multicenter study we report the outcome of 106 WM patients (69 male) who underwent an Allo-SCT between 1989 and 2005 and were reported to the EBMT Lymphoma Database. The median age at transplant was 49 years (21–65), and the median time from diagnosis to SCT was 34 months (5–310). The median number of treatment lines prior to allo-SCT was 3(1–10) and 19 patients had failed a prior autograft. Ten (10%) patients were in 1st maximum response (MR), 35 (33%) in PR1, 29 (27%) in PR≥2 and 32 (30%) had refractory disease at the time of transplantation. Forty-four patients were treated with conventional (CT) conditioning protocols; [Cy/TBI n=24, Melphalan/TBI, n=6, BuCy n=14] and 62 with a reduced intensity protocol (RIC); [Fludarabine based regimen n=43, Low dose TBI/Cy n=19] With a median follow up of 31 months (3 to 169) 59 (56%) patients, are alive and free of disease. Forty-eight (45%) patients developed aGVHD [Grades I-II (n=34), Grades III-IV (n=14)] with no statistically significant difference between conventional and RIC groups. Five out of nine RIC patients developed aGVHD following the administration of donor lymphocytes for either residual disease or mixed chimerism. Sixteen patients (15%) developed limited and 11 (10%) extensive chronic GVHD. Seventeen (16%) patients relapsed at a median time of 8 (1–89) months after allo-SCT. Thirty-five (33%) patients died, 5 (5%) from disease relapse or progression and 30 (28%) from regimen toxicity. Non-relapse mortality rates were estimated of 30% and 33%, at 1 and 3 years, respectively, for the CT group, and 24% and 30% for the RIC group of patients. Relapse rates at 1 and 3 years were 10%, 12% for the CT group and 14% and 25% for the RIC. Progression free survival (PFS) rates were 60%, 54% and 54% at 1, 3 and 5 years for the CT and 61%, 44% and 39% for the RIC patients. Overall survival was 65%, 59% and 59% for the CT and 71%, 66% and 66% for the RIC at 1, 3 and 5 years, respectively. Multivariate analysis showed that chemorefractory disease at allo-SCT was associated with a significantly higher relapse rate [p<0.03; 95% CI 1.1–8.9] while the use of TBI in the conditioning regimen with a significantly lower relapse rate [p<0.02; 95% CI 1.1–9.3]. There were no differences in outcome when considering the intensity of the conditioning regimen. In conclusion, allo-SCT is a feasible and well-tolerated procedure in this group of elderly patients with advanced disease. In addition, relapse rate after the allogeneic procedure is low resulting in a good long-term outcome.

Cytarabine Either with Induction or Conditioning May Improve Outcomes Among Those Undergoing Autologous Transplantation in First or Second Remission for Mantle Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4546-4546
Author(s):  
Bijal D. Shah ◽  
Bryan J Little ◽  
Jennifer Cultrera ◽  
Celeste M. Bello ◽  
Lubomir Sokol ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Published Data ◽  
Free Survival ◽  
Improve Outcome ◽  
Significant Difference ◽  
Mantle Cell

Abstract Abstract 4546 Introduction: Consolidation with autologous transplantation (AutoSCT) may extend progression free survival when administered following initial induction. Published data suggest intensive cytarabine containing induction may improve outcome when administered prior to autologous transplantation. Methods: We retrospectively evaluated all patients with MCL transplanted at our institution before 2010. We identified 57 patients, among whom 52 were transplanted in first or second remission. Results: 21 patients had received a cytarabine containing induction (most commonly R-HyperCVAD), among whom 14 also received cytarabine as a component of conditioning (BEAM+/−R). The most common induction in the remaining patients was R-CHOP. Among the 31 who did not receive a cytarabine based induction, 23 received cytarabine as a component of the pre-transplant conditioning regimen (BEAM+/−R). The median PFS for those getting cytarbine with induction and conditioning was approximately 28 months (at which time 51% of patients continued without progression). The median PFS for those getting cytarabine with conditioning only was approximately 38 months (at which time 47% continued without progression). Logrank analysis shows no statistically significant difference between these groups (p one-sided = 0.29). Alternatively, those who did not receive any cytarabine had a median PFS of 20 months, with no survival beyond 33 months. Logrank analysis shows this to be inferior to those receiving cytarabine with induction/conditioning (p one-sided = 0.049), as well as among those who received cytarabine with conditioning only (p one-sided = 0.001). Conclusions: In the absence of randomized comparisons it is difficult to draw firm conclusions on the role of induction. These analyses would suggest that among those with chemosensitive disease able to proceed to transplant, more modern conditioning with cytarabine containing regimens may make up for lack of exposure to this agent during induction. Disclosures: Sokol: Celgene: Honoraria, Speakers Bureau.

Reduced-Intensity Regimens in Allogeneic Stem-Cell Transplantation for Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia

Hematology ◽  
2006 ◽  
Vol 2006 (1) ◽  
pp. 390-397 ◽  
Author(s):  
Issa F. Khouri
Keyword(s):  
Stem Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Allogeneic Transplantation ◽  
Lymphocytic Leukemia ◽  
Lymphoid Malignancies ◽  
Reduced Intensity

AbstractAutologous stem-cell transplantation is widely accepted as effective therapy for patients with relapsed aggressive B-cell non-Hodgkin lymphomas. Although 40–60% of younger patients with diffuse large cell lymphoma can expect to be cured, substantial numbers will experience a relapse. In addition, certain histologic subtypes are associated with particularly poor prognoses with combination chemotherapy alone (e.g., mantle cell lymphoma). Relatively few of these patients will experience long-term responses. Although other NHL subtypes are associated with more favorable prognoses in terms of overall survival, they are rarely cured (e.g., follicular lymphoma, chronic lymphocytic leukemia). Allogeneic transplantation has been increasingly utilized in patients with lymphoid malignancies but is associated with high toxicity. Recently, reduced-intensity conditioning regimens have shown encouraging results, attributed to graft-versus-lymphoma effects. This article discusses changes in the way autologous and allogeneic transplants may be carried out in the future to treat patients with lymphoid malignancies.

Treatment of feline gastrointestinal intermediate- or large-cell lymphoma with lomustine chemotherapy and 8 Gy abdominal cavity radiation therapy

2020 ◽  
pp. 1098612X2095960
Author(s):  
Tracy L Gieger ◽  
Gabriela S Seiler ◽  
Michael W Nolan
Keyword(s):  
Radiation Therapy ◽  
Survival Time ◽  
Cell Lymphoma ◽  
Abdominal Cavity ◽  
Treatment Protocol ◽  
Progression Free Survival ◽  
Large Cell ◽  
Response To Treatment ◽  
Cavity Radiation ◽  
Large Cell Lymphoma

Objectives The goal of this study was to document the outcomes and toxicity of a novel multimodality treatment protocol for feline gastrointestinal intermediate- or large-cell lymphoma (FGL) in which cats were treated at 21-day intervals. Methods This was a prospective, single-arm study. Twelve client-owned cats with cytologically diagnosed FGL were treated with a combination of abdominal cavity radiation therapy (RT; 8 Gy total dose administered in two 4 Gy fractions, 21 days apart), lomustine chemotherapy (approximately 40 mg/m2, administered orally at 21-day intervals for four treatments), prednisolone (5 mg PO q24h) and cobalamin (250 µg/week SC). Results Three cats were euthanized prior to the second treatment and it was difficult to discern treatment-associated toxicity from progressive disease. Four of the remaining cats developed cytopenias, resulting in 7–14-day lomustine treatment delays and/or dose reductions. Six cats had a partial response to treatment and three had stable disease based on ultrasound at day 21 (50% overall response rate). Three of these six cats completed the study and lived >240 days; one died of refractory diabetes mellitus with no clinical evidence of FGL, and the other two died as a result of FGL. The median overall survival time was 101 days (95% confidence interval [CI] 9–240). The median progression-free survival time was 77 days (95% CI 8–212). Necropsies were performed in eight cats, which revealed multifocal lymphoma throughout the gastrointestinal tract and other organs. Conclusions and relevance Oncological outcomes reported herein are comparable to those achieved with multiagent injectable chemotherapy (eg, CHOP). Treatment was seemingly well tolerated in most cats and was relatively cost-effective. It is therefore plausible that improved disease control may be achievable through continued optimization and intensification of the combinatorial chemoradiotherapy protocol.

Human leukocyte antigen (HLA) DR4 is associated with inferior progression free survival (PFS) following allogeneic hematopoietic stem cell transplantation (allo HSCT) for lymphoid malignancies

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6543-6543
Author(s):  
C. Aggarwal ◽  
S. Gupta ◽  
T. Hahn ◽  
S. Padmanabhan ◽  
P. L. McCarthy ◽  
...  
Keyword(s):  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Human Leukocyte ◽  
Progression Free Survival ◽  
Disease Stage ◽  
Hematopoietic Stem ◽  
Lymphoid Malignancies ◽  
Increased Sensitivity ◽  
Total Body

6543 Background: HLA DR4 is associated with autoimmune disorders and response to cyclosporine immunosuppression in T-cell Large Granular Lymphoproliferative Disorder (BJH 2003;123(3)). We investigated the HLA DR4 role on graft-versus-host disease (GVHD) and graft-versus-leukemia effect in HLA-matched HSCT performed for lymphoid malignancies. Methods: We retrospectively reviewed 77 related and 22 unrelated consecutive allo HSCT patients (pts) treated between 1992 and 2003 at RPCI to investigate the influence of HLA DR4 on overall survival (OS), PFS and grade 2–4 acute and chronic GVHD (cGVHD) incidence. HLA DR B1 typing was determined by molecular (n=69) or serologic (n=30) methods. The pt proportion with one or two HLA DR4 antigens was 18% (18/99), similar to the general Caucasian population. Pt characteristics included: ALL (n=41), CLL (n=4), HD (n=7) and NHL (n=47); median age 36 y (range 6–64); Male (n=65), Female (n=34); Caucasian (>95%); Total Body Irradiation (TBI) conditioning regimens (n=79); Busulfan/Cyclophosphamide (BuCy) (n=6), Thiotepa/TBI (n=23), Cy/TBI (n=9), Etoposide/Cy/TBI (n=9), Fludarabine/Melphalan (n=8), Thiotepa/Carboplatin (n=8) or other combinations (n=6). Results: There was no difference in OS between the HLA DR4 positive vs negative pts in any disease or donor subgroups (p=0.25). Nine of 18 DR4 positive pts (50%) and 20 of the 81 DR4 negative pts (25%) had disease progression (p=0.033). PFS at 33 months was 70% in the DR4 negative group and 30% in the DR4 positive group (p=0.004). In a univariate analysis, DR4 positivity, conditioning regimen and disease stage at HSCT were significant factors for PFS. However in the multivariate analysis, DR4 positivity was the only significant factor for PFS (RR=3.2, p=0.007). By preliminary analysis, 0/18 of the HLA DR4 positive pts and 13/81 HLA DR4 negative pts developed cGVHD (p=0.06). Conclusions: These results suggest that HLA DR4 positive pts have reduced cGVHD leading to increased relapse and decreased PFS with no effect on OS. Increased sensitivity of HLA DR4 lymphocytes to GVHD prophylaxis agents or reduced binding affinity for the CD4 coreceptor are possible reasons for these observations. No significant financial relationships to disclose.

scholarly journals Analysis with antiidiotype antibody of a patient with chronic lymphocytic leukemia and a large cell lymphoma (Richter's syndrome)

Blood ◽  
1987 ◽  
Vol 70 (1) ◽  
pp. 45-50 ◽  
Author(s):  
LF Bertoli ◽  
H Kubagawa ◽  
GV Borzillo ◽  
M Mayumi ◽  
JT Prchal ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Plasma Cells ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Lymphocytic Leukemia ◽  
Immunoglobulin Gene ◽  
Anaplastic Lymphoma ◽  
Large Cell Lymphoma ◽  
Richter’S Syndrome

Abstract A murine monoclonal antibody made against an idiotypic determinant (Id) of surface IgM/IgD lambda molecules on chronic lymphocytic leukemia (CLL) cells of a 71-year-old woman was used for clonal analysis by two- color immunofluorescence. The anti-Id antibody identified IgM+/IgD+/lambda+ B cells as the predominant cell type of her CLL clone. In addition, substantial proportions of the IgG and IgA B cells and most of the IgM plasma cells in her bone marrow and blood were Id+. Six years after diagnosis, the patient died of respiratory failure due to infiltration of lungs by malignant cells. Autopsy revealed a dramatic change in the tumor cell morphology. The lungs, hilar nodes, and liver were infiltrated by a diffuse large cell lymphoma admixed with the leukemic cells. By immunohistologic staining these anaplastic lymphoma cells were IgM+/IgD-/lambda+ B cells expressing the same Id noted earlier on the CLL cells. The immunoglobulin gene rearrangement pattern on Southern blot analysis was also the same in leukemic blood cells and in the tissues involved by the lymphoma. Thus, the combination of antiidiotype and immunoglobulin gene analyses in this patient with Richter's syndrome revealed that a CLL clone, seemingly “frozen” in differentiation, was actually undergoing isotype switching, differentiation into plasma cells, and evolution into a rapidly growing and fetal lymphoma.

scholarly journals The biology behind B-cell lymphoma 2 as a target in chronic lymphocytic leukemia

2016 ◽  
Vol 7 (6) ◽  
pp. 321-329 ◽  
Author(s):  
Valentín Ortíz-Maldonado ◽  
Pablo Mozas ◽  
Julio Delgado
Keyword(s):  
Clinical Trials ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Mitochondrial Pathway ◽  
Therapeutic Agents ◽  
Lymphocytic Leukemia ◽  
Hallmarks Of Cancer ◽  
Lymphoid Malignancies

B-cell lymphoma 2 (BCL2)-type proteins are key regulators of the intrinsic or mitochondrial pathway for apoptosis. Since escape from apoptosis is one the main ‘hallmarks of cancer’, BCL2 inhibitors have emerged as promising therapeutic agents for diverse lymphoid malignancies, particularly chronic lymphocytic leukemia (CLL). Multiple clinical trials have shown efficacy of these agents in patients with relapsed/refractory disease with a favorable toxicity profile. Moreover, some clinical trials indicate that combination with monoclonal antibodies and other novel agents may enhance their effect.

scholarly journals Peritransplant Ruxolitinib Administration is Safe and Effective in Patients with Myelofibrosis: a Pilot Open-Label Study

2021 ◽  
Author(s):  
Haris Ali ◽  
Ni-Chun Tsai ◽  
Timothy Synold ◽  
Sally Mokhtari ◽  
Weimin Tsai ◽  
...  
Keyword(s):  
Chronic Gvhd ◽  
Pilot Trial ◽  
Conditioning Regimen ◽  
Kidney Injury ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Open Label ◽  
Gvhd Prophylaxis ◽  
Matched Sibling ◽  
Grade 3

We report results of our prospective pilot trial (NCT02917096) evaluating safety/feasibility of peri-transplant administration of ruxolitinib for myelofibrosis treatment. Primary objectives were to determine the safety and identify maximum tolerated dose (MTD) of ruxolitinib. Ruxolitinib was given at two dose levels (DL) of 5 and 10mg twice daily, with fludarabine/melphalan conditioning regimen and tacrolimus/sirolimus GVHD prophylaxis. We enrolled 6 and 12 patients in DL-1 and DL-2, respectively. Median age at transplant was 65 years (range:25-73) for all patients. Per DIPSS, 4 patients were at high and 14 were at intermediate risk. PBSCs was the graft source from a matched sibling (n=5) or unrelated (n=13) donor. At each DL one patient developed DLTs: Grade 3 cardiac and GI with Grade 4 pulmonary in DL-1 and Grade 3 kidney injury in DL-2. All patients achieved engraftment. Cumulative incidence (CI) of acute GVHD grade 2-4 and 3-4 were 17% (95% CI: 6-47) and 11% (95% CI: 3-41), respectively. CI of 1-year chronic GVHD was 42% (95% CI: 24-74). With the median follow-up of 22.6 months (range:6.2-25.8) in surviving patients the 1-year overall and progression free survival were 77% (95% CI: 50-91) and 71% (95% CI: 44-87), respectively. Causes of death (n=4) were cardiac arrest, GVHD, respiratory failure, and refractory GVHD of liver. Our results showed that peri-HCT ruxolitinib was safe and well-tolerated with the MTD determined as 10 mg BID, associated with dose-dependent PK and cytokine profile. The early efficacy data are highly promising in this group of high-risk older patients with MF.

Peripheral T-Cell Lymphoma Arising in Patients With Chronic Lymphocytic Leukemia

2019 ◽  
Vol 152 (6) ◽  
pp. 818-827
Author(s):  
Bianca M Van Der Nest ◽  
Connull Leslie ◽  
David Joske ◽  
Dejan Radeski ◽  
Rohen White ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Lymphocytic Leukemia ◽  
Emission Tomography ◽  
Peripheral T Cell Lymphoma ◽  
Positron Emission ◽  
History Of ◽  
Large Cell Lymphoma ◽  
Management Recommendations

Abstract Objectives To describe three further cases of anaplastic large cell lymphoma (ALCL) occurring in patients with preexisting chronic lymphocytic leukemia (CLL). We also reviewed the literature of previously published cases. Methods We discuss the clinical features, histopathology, and outcomes for three patients with ALCL and CLL from Perth, Australia. The cases were also included in a literature review of existing cases and comparisons were made with our cohort. Results The three patients included two men (aged 77 and 74 years) and one woman (aged 66 years). All had a history of untreated CLL with diagnosis established 4 to 16 years before. They had lymphadenopathy and/or cutaneous/soft tissue lesions that proved to be ALCL, ALK+ (one case) or ALCL, ALK– (two cases). Conclusions Further research is required in this area to establish prognostic and management recommendations. Increasing numbers of cases are being described. Positron emission tomography with computed tomography was not useful in our cohort for diagnosing progression.

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