Search

Encouraging results have been reported with sirolimus, tacrolimus and low-dose methotrexate after non-myeloablative allogeneic hematopoietic cell transplant. We conducted a retrospective analysis of 71 patients with lymphoid malignancies treated with this prophylaxis regimen after non-myeloablative or reduced intensity allogeneic hematopoietic cell transplant. Grafts were human leukocyte antigen (HLA)-matched related in 29 (41%), matched unrelated in 36 (51%) and 9/10 HLA-matched unrelated in six (8%) patients. The regimen was well tolerated and over 90% of patients completed the planned treatment. The cumulative incidences of 1-year grade B-D and C-D acute graft-versus-host disease (GVHD) were 0.28 (95% confidence interval [CI], 0.18-0.39) and 0.07 (95% CI, 0.03-0.15), respectively, and of 1- and 2-year chronic GVHD (National Institutes of Health criteria) in 70 evaluable patients were 0.15 (95% CI, 0.08-0.24) and 0.33 (95% CI, 0.22-0.44), respectively. The median day of onset of acute GVHD was 123 days (range, 17-268 days). Peri-transplant rituximab or anti-thymocyte globulin did not affect GVHD. The cumulative incidence of 1-year non-relapse mortality and relapse were 4% and 20%, respectively. With a median follow-up of 3.5 (range: 0.18-5.1) years, overall survival and progression-free survival at 2 years were 82% and 66%, respectively. This GVHD regimen results in a low incidence and severity of acute and chronic GVHD after reduced intensity and non-myeloablative allogeneic hematopoietic cell transplant for lymphoid malignancies. The study also highlights the incidence of late onset acute GVHD in non-myeloablative/reduced intensity conditioning, and the contribution of the new GVHD staging system that more accurately reflects clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective To investigate the usefulness of various scales for evaluating joint and fascia manifestations in patients with chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation, and to compare the scales in terms of simplicity of use and ability to yield reliable and clinically meaningful results. Methods In a prospective, multicenter, longitudinal, observational cohort of patients with chronic GVHD (n = 567), we evaluated 3 scales proposed for assessing joint status: the National Institutes of Health (NIH) joint/fascia scale, the Hopkins fascia scale, and the Photographic Range of Motion (P-ROM) scale. Ten other scales were also tested for assessment of symptoms, quality of life, and physical functions. Results Joint and fascia manifestations were present at study enrollment in 164 (29%) of the patients. Limited range of motion was most frequent at the wrists or fingers. Among the 3 joint assessment scales, changes in the NIH scale correlated with both clinician- and patient-perceived improvement of joint and fascia manifestations, with higher sensitivity than the Hopkins fascia scale. Changes in all 3 scales correlated with clinician- and patient-perceived worsening, but the P-ROM scale was the most sensitive in this regard. Onset of joint and fascia manifestations was not associated with subsequent mortality. Conclusion Joint and fascia manifestations are common in patients with chronic GVHD and should be assessed carefully in these patients. Our results support the use of the NIH joint/fascia scale and P-ROM scale to assess joint and fascia manifestations. The NIH scale better captures improvement, while the P-ROM scale better captures worsening. The utility of these scales could also be tested in the rheumatic diseases. [ABSTRACT FROM AUTHOR]

Abstract: Consolidation with allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides a survival benefit to patients with acute lymphoblastic leukemia (ALL). We have previously reported comparable survival and relapse rates after T cell–depleted (TCD) allo-HSCT compared with unmodified transplantations for acute myelogenous leukemia, myelodysplastic syndrome, and non-Hodgkin lymphoma with significantly decreased graft-versus-host disease (GVHD). We performed a 56-patient retrospective study to evaluate TCD allo-HSCT for the treatment of ALL after myeloablative total body irradiation–based therapy. The 2-year and 5-year overall survival rates for patients with ALL after TCD allo-HSCT were 0.39 (95% confidence interval [CI], 0.26-0.52) and 0.32 (95% CI, 0.19-0.44), respectively, and the 2-year and 5-year disease-free survival rates were 0.38 (95% CI, 0.25-0.50) and 0.32 (95% CI, 0.20-0.44). There was a trend toward improved survival of patients who underwent TCD allo-HSCT in first complete remission compared with those who did so in other remission states. The cumulative incidence of grade II-IV acute GVHD at 1 year was 0.20 (95% CI, 0.10-0.31), and no patients developed grade IV acute GVHD. The cumulative incidence of chronic GVHD in 41 evaluable patients at 2 and 5 years was 0.15 (95% CI, 0.04-0.26), and that of extensive chronic GVHD at 2 and 5 years was 0.05 (95% CI, 0-11.6). We demonstrate OS and DFS rates that compare favorably to unmodified allo-HSCT with lower rates of GVHD. [Copyright &y& Elsevier]

Peripheral T-cell non-Hodgkin lymphomas (T-NHL) are rare diseases, with a worse prognosis compared to their B-cell counterparts. Allogeneic hematopoietic stem cell transplant may have a role in the treatment of relapsed/refractory disease or high-risk histologies in the upfront setting. However, there is limited information on the efficacy of allogeneic transplant for these diseases, as well as what factors may predict outcomes. We therefore performed a retrospective study of 34 patients who received an allogeneic transplant for the treatment of T-NHL at a single center between 1 January 1992 and 31 December 2009. The median follow-up for survivors was 45 months (range 9-160 months). The 2-year overall survival (OS) was 0.61 (95% confidence interval [CI]: 0.43-0.75) with a plateau at 28 months. Ki-67 expression ≤ 25% was predictive of improved OS ( p < 0.01), and transplant in complete remission was predictive of a decreased cumulative incidence of events ( p = 0.04). Three patients received a donor leukocyte infusion, and two patients demonstrated a response, supporting a graft-versus-lymphoma effect. These data demonstrate that allogeneic transplant is a viable option for the treatment of T-NHL and merits prospective evaluation. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for patients with myelodysplastic syndrome (MDS). Donor T cells are critical for the graft-versus-tumor effect but carry the risk of graft-versus-host disease (GVHD). CD34 selection with immunomagnetic beads has been an effective method of depleting alloreactive donor T cells from the peripheral blood graft and has been shown to result in significant reduction in acute and chronic GVHD. We analyzed the outcomes of 102 adults (median age, 57.6 years) with advanced MDS who received a CD34-selected allo-HSCT between January 1997 and April 2012 at Memorial Sloan Kettering Cancer Center. The cumulative incidences of grades II to IV acute GVHD were 9.8% at day 100 (95% confidence interval [CI], 5.0% to 16.5%) and 15.7% at day 180 (95% CI, 9.4% to 23.4%). The cumulative incidence of chronic GVHD at 1 year was 3.9% (95% CI, 1.3% to 9.0%). The cumulative incidences of relapse were 11.8% at 1 year (95% CI, 6.4% to 18.9%) and 15.7% at 2 years (95% CI, 9.4% to 23.4%). Forty-eight patients were alive with a median follow-up of 71.7 months. Rates of overall survival (OS) were 56.9% at 2 years (95% CI, 48% to 67.3%) and 49.3% at 5 years (95% CI, 40.4% to 60.2%). Rates of relapse-free survival (RFS) were 52.0% at 2 years (95% CI, 41.9% to 61.1%) and 47.6% at 5 years (95% CI, 37.5% to 56.9%). The cumulative incidences of nonrelapse mortality were 7.8% at day 100 (95% CI, 3.7% to 14.1%), 22.5% at 1 year (95% CI, 15.0% to 31.1%), and 33.4% at 5 years (95% CI, 24.2% to 42.6%) post-transplant. The incidence of chronic GVHD/RFS overlapped with RFS. These findings demonstrate that ex vivo T cell–depleted allo-HSCT by CD34 selection offers long-term OS and RFS with low incidences of acute and chronic GVHD and without an increased risk of relapse. [ABSTRACT FROM AUTHOR]

The relationship between intestinal microbiota composition and acute graft-versus-host disease (GVHD) after allogeneic blood/marrow transplantation (allo-BMT) is not well understood. Intestinal bacteria have long been thought to contribute to GVHD pathophysiology, but recent animal studies in nontransplant settings have found that anti-inflammatory effects are mediated by certain subpopulations of intestinal commensals. Hypothesizing that a more nuanced relationship may exist between the intestinal bacteria and GVHD, we evaluated the fecal bacterial composition of 64 patients 12 days after BMT. We found that increased bacterial diversity was associated with reduced GVHD-related mortality. Furthermore, harboring increased amounts of bacteria belonging to the genus Blautia was associated with reduced GVHD lethality in this cohort and was confirmed in another independent cohort of 51 patients from the same institution. Blautia abundance was also associated with improved overall survival. We evaluated the abundance of Blautia with respect to clinical factors and found that loss of Blautia was associated with treatment with antibiotics that inhibit anaerobic bacteria and receiving total parenteral nutrition for longer durations. We conclude that increased abundance of commensal bacteria belonging to the Blautia genus is associated with reduced lethal GVHD and improved overall survival. [ABSTRACT FROM AUTHOR]

While cord blood transplantation (CBT) is an effective therapy for hematologic malignancies, acute graft-versus-host disease (aGVHD) is a leading cause of transplant-related mortality (TRM). We investigated if biomarkers could predict aGVHD and TRM after day 28 in CBT recipients. Day 28 samples from 113 CBT patients were analyzed. Suppressor of tumorigenicity 2 (ST2) was the only biomarker associated with grades ll-IV and lll-IV aGVHD and TRM. Day 180 grade lll-IV aGVHD in patients with high ST2 levels was 30% (95% confidence interval [Cl], 18-43) vs 13% (95% Cl, 5-23) in patients with low levels (P = .024). The adverse effect of elevated ST2 was independent of HLA match. Moreover, high day 28 ST2 levels were associated with increased TRM with day 180 estimates of 23% (95% Cl, 13-35) vs 5% (95% Cl, 1-13) if levels were low (P = .001). GVHD was the most common cause of death in high ST2 patients. High concentrations of tumor necrosis factor receptor-1, interleukin-8, and regenerating islet-derived protein 3-a were also associated with TRM. Our results are consistent with those of adult donor allografts and warrant further prospective evaluation to facilitate future therapeutic intervention to ameliorate severe aGVHD and further improve survival after CBT. [ABSTRACT FROM AUTHOR]