Fludarabine/Melphalan 100 mg/m(2) Conditioning Therapy Followed by Allogeneic Hematopoietic Cell Transplantation for Adult Patients with Secondary Hemophagocytic Lymphohistiocytosis.

Our previous research indicated that a reduced-intensity conditioning regimen (fludarabine and melphalan at 100 mg/m2) was useful in allogeneic hematopoietic cell transplantation (HCT) for patients with lymphoma. This retrospective study evaluated the reduced-intensity conditioning regimen in allogeneic HCT for adult patients with hemophagocytic lymphohistiocytosis (HLH). Sixteen patients with HLH were evaluated, including 6 patients who were enrolled in a prospective clinical trial (NCT00772811) and 10 patients who received the same conditioning regimen (fludarabine at 30 mg/m2/day on days -6 to -2 and melphalan at 100 mg/m2 on day -2). The median age was 42 years (range, 18 to 64), and 12 patients had Epstein-Barr virus (EBV)-associated HLH. Donors were an HLA matched sibling for 10 patients, an unrelated matched volunteer for 4 patients, and a mismatched family member for 2 patients. After excluding 3 patients who died soon after HCT, 12 patients achieved an engraftment (neutrophil median, day 12; platelet median, day 16). Five patients experienced acute graft-versus-host disease (GVHD), including 1 case of grade II and 4 cases of grades III to IV. Chronic GVHD occurred in 3 patients (moderate, 1 case; severe, 2 cases). After a median follow-up of 33.8 months 1 patient progressed, 3 patients relapsed, and 9 patients died. Five deaths were unrelated to relapse or progression and were caused by infection (n = 3), bleeding (n = 1), and GVHD (n = 1). No deaths or relapses were observed at >124 days post-transplant. The overall survival rate was 48.6%, and significant differences were observed according to pretransplant ferritin level (P = .007) and cytopenia lineage (P = .021). Before allogeneic HCT 10 of 12 patients still tested positive for EBV DNA: 6 patients tested negative for EBV DNA after HCT, 2 patients had persistent EBV DNA, and 2 patients were unassessable because of early death. Conditioning therapy using a lower dose of melphalan combined with fludarabine appears to be promising in allogeneic HCT for adults with HLH. However, strategies are needed to reduce the risk of early death.

Park HS ，Lee JH ，Lee JH ，Choi EJ ，Ko SH ，Seol M ，Lee YS ，Kang YA ，Jeon M ，Lee KH ... -  《-》

Reduced-intensity conditioning hematopoietic cell transplantation is an effective treatment for patients with SLAM-associated protein deficiency/X-linked lymphoproliferative disease type 1.

X-linked lymphoproliferative disease type 1 (XLP1) is a rare immune deficiency caused by mutations in SH2D1A. Allogeneic hematopoietic cell transplantation (HCT) is often performed because of the morbidity and mortality associated with XLP1. There is limited experience using reduced-intensity conditioning (RIC) regimens for these patients. Here we report our 8-year single-center experience. Sixteen consecutive patients diagnosed with XLP1 underwent allogeneic HCT between 2006 and 2013 after a RIC regimen consisting of alemtuzumab, fludarabine, and melphalan. Patient phenotypes included hemophagocytic lymphohistiocytosis (HLH) after Epstein-Barr virus (n = 5) or human herpesvirus 6 (n = 1), macrophage activation syndrome (n = 1), interstitial pneumonitis and encephalitis (n = 1), B cell lymphoma (n = 8), and hypogammaglobulinemia (n = 2). One patient was asymptomatic. Fourteen of 16 patients received 8/8 HLA-matched unrelated or related bone marrow grafts, whereas 2 patients received mismatched unrelated grafts. Acute graft-versus-host disease (GVHD) prophylaxis consisted of methylprednisolone and cyclosporine in all but 1 patient, who additionally received methotrexate. All patients had hematopoietic recovery. There were no cases of hepatic veno-occlusive disease or pulmonary hemorrhage. One patient (6%) developed acute GVHD and later also developed chronic GVHD (6%). Five patients (31%) developed mixed chimerism. Only 1 patient with mixed chimerism (6%) experienced a decline of donor chimerism to less than 50% but returned to full donor chimerism after infusion of donor lymphocytes and a CD34(+) selected stem cell boost. Infectious complications were frequent, particularly viral reactivation. One-year survival estimated by Kaplan-Meier analysis was 80%, with long-term survival estimated at 71%. Survival was similar for patients with or without a history of HLH (86% versus 75%, respectively, P = .70). There were no occurrences of lymphoma or HLH after HCT. RIC HCT with alemtuzumab, fludarabine, and melphalan is an effective treatment for patients with XLP1, offering good survival rates regardless of prior disease manifestations, including HLH.

Marsh RA ，Bleesing JJ ，Chandrakasan S ，Jordan MB ，Davies SM ，Filipovich AH ... -  《-》

Reduced toxicity conditioning and allogeneic stem cell transplantation in adults using fludarabine, carmustine, melphalan, and antithymocyte globulin: outcomes depend on disease risk index but not age, comorbidity score, donor type, or human leukocyte ant

Slack JL ，Dueck AC ，Fauble VD ，Sproat LO ，Reeder CB ，Noel P ，Khera N ，Betcher JA ，Klein JL ，Leis JF ，Adams RH ... -  《-》

Reduced-intensity conditioning for hematopoietic cell transplant for HLH and primary immune deficiencies.

Allen CE ，Marsh R ，Dawson P ，Bollard CM ，Shenoy S ，Roehrs P ，Hanna R ，Burroughs L ，Kean L ，Talano JA ，Schultz KR ，Pai SY ，Baker KS ，Andolina JR ，Stenger EO ，Connelly J ，Ramirez A ，Bryant C ，Eapen M ，Pulsipher MA ... -  《-》

A Phase II Trial of Fludarabine/Melphalan 100 Conditioning Therapy Followed by Allogeneic Hematopoietic Cell Transplantation for Patients With Lymphoma.

Conditioning therapy with fludarabine and melphalan 140 mg/m(2) has been widely used before allogeneic hematopoietic cell transplantation (HCT) for lymphoma. A lower dose of melphalan might result in lower mortality and morbidity without compromising engraftment. In our phase II trial, we investigated a conditioning regimen of fludarabine (30 mg/m(2)/day for 5 days on days -6 to -2) and melphalan (100 mg/m(2) on day -2). Antithymocyte globulin was added to fludarabine and melphalan for unrelated or mismatched familial donor HCT. The present study included 26 patients with lymphoma (B-cell in 10, T-cell in 11, and natural killer/T-cell lymphoma in 2). An objective tumor response after HCT was observed in 18 patients (75.0%; complete in 14 and partial in 4). Acute and chronic graft-versus-host disease (GVHD) occurred in 23.1% and 55.0% of the assessable patients, respectively. The 5-year overall survival, nonrelapse mortality, progression-free survival, and event-free survival rate was 40.4%, 21.6%, 39.2%, and 30.8%, respectively. Donor lymphocyte infusions were given to 3 patients who had developed a relapse or progression after HCT, and 2 of whom had a showed partial response. Patients with severe chronic GVHD had greater overall survival than those with no, mild, or moderate chronic GVHD. Conditioning therapy with a lower dose of melphalan, combined with fludarabine, appears to be promising in allogeneic HCT for lymphoma. The Clinicaltrials.gov identification number for the present study is NCT00772811.

Lee JH ，Lee JH ，Kim DY ，Seol M ，Lee YS ，Kang YA ，Jeon M ，Lee KH ... -  《-》