Herpes zoster prophylaxis with low-dose acyclovir in patients with malignant lymphoma and multiple myeloma treated with autologous stem cell transplantation.

BACKGROUND: Herpes zoster (HZ) is a frequent complication after autologous stem cell transplantation (ASCT). The option of zoster prophylaxis with an antiviral drug is described in the literature, but there is no consensus on the drug and the dosage. PATIENTS AND METHODS: We analyzed the records of 310 patients treated with ASCT who were controlled regularly regarding HZ inter alia for at least 24 months following ASCT. Since 01/2015 patients received prophylactic low-dose acyclovir (400 mg per day) during the first 12 months following discharge after ASCT (n = 107). RESULTS: Twenty percent of patients without this kind of prophylaxis and 2.8% of patients with prophylaxis developed HZ (p < .001). No patient with this prophylaxis developed HZ in the first year after ASCT, 2.8% of patients in the second year after ASCT. A prognostic factor was the kind of diagnosis: 30% of lymphoma patients and 14% of myeloma patients developed HZ in the first 24 months after ASCT without prophylaxis, but only 6.3% and 0% of patients with prophylaxis, respectively. Neither an increase of HZ cases following prophylaxis nor acyclovir refractory HZ cases were observed. CONCLUSIONS: Zoster prophylaxis with low-dose acyclovir over 12 months after ASCT is effective and well tolerated.

Long-term remissions in patients with early relapse of diffuse large B-cell lymphoma following high-dose chemotherapy, autologous stem cell transplantation, and radiotherapy of residual disease.

PURPOSE: The prognosis of an early relapse of diffuse large B-cell lymphoma (DLBCL) appears to be poor following autologous stem cell transplantation (ASCT). The aim of this study is to contribute data to the open question on whether additional radiotherapy can improve the outcome. PATIENTS AND METHODS: Forty-eight patients with an early relapse (median 4 months after the end of initial immunochemotherapy, range 1-11) of DLBCL have been treated in our institution with high-dose therapy (usually the BEAM protocol) and ASCT since 2008 (median age 61 years, range 28-73). Twenty-three patients received ASCT in a second treatment line, 25 in a third line (19 refractory to second-line salvage therapy, 5 after second relapse). Fifteen of these 48 patients received radiotherapy (36-50 Gy, median 40) of residual masses after ASCT. RESULTS: Three-year overall survival (OS) and progression-free survival (PFS) after second-line ASCT were 61 and 57%, after third-line ASCT 47 and 44%, respectively, without significant differences. A prognostic factor was the International Prognostic Index (IPI) at the start of salvage therapy. Three-year OS and PFS in low-risk patients were 69 and 69%, in low-intermediate-risk 63 and 53%, and in high-intermediate-risk 23 and 23%, respectively (p = 0.033). Twenty-three patients achieved a sustained complete remission (13-146 months, median 62). CONCLUSION: Sustained long-term remissions can be achieved in patients with early relapse of DLBCL following ASCT in a second or third treatment line, particularly in patients with low- and low-intermediate-risk IPI, following radiotherapy of residual disease after ASCT. Further investigations are required to clarify which patients need an alternative therapy (potentially CAR T­cells or allogeneic transplantation).

Long-term outcome in patients with follicular lymphoma following high-dose therapy and autologous stem cell transplantation.

OBJECTIVE: To contribute data on long-term outcome and potential curative impact of ASCT in FL, especially following HDT with the BEAM protocol (BCNU, etoposide, cytarabine and melphalan), given very limited data on this topic in the literature. PATIENTS AND METHODS: Patients with FL (n = 76) were treated in our institution with HDT and ASCT. In the case of long-term remission (≥8 years), peripheral blood was tested for minimal residual disease by t(14;18)- and IGH-PCR, including the last follow-up. RESULTS: 10-year overall survival, progression-free survival, and freedom from progression (FFP) after first-line ASCT (n = 20) were 80%, 60%, and 69%, after second-line ASCT (n = 48, following BEAM) 66%, 38%, and 41%, after third/fourth-line ASCT (n = 8) 33%, 25%, and 25%, respectively. Prognostic factors for FFP were treatment line and FLIPI (Follicular Lymphoma International Prognostic Index). 10-year FFP for second-line ASCT and low-risk FLIPI at relapse was 69%, intermediate-risk 28%, and high-risk 25% (P < .05). 26 patients developed sustained long-term clinical and molecular remissions of up to 27 years. CONCLUSIONS: Sustained long-term clinical and molecular complete remissions up to 27 years can be achieved following ASCT (including HDT with BEAM in second treatment line), indicating a potential curative impact of ASCT in FL.

Long-term clinical and molecular remissions in patients with mantle cell lymphoma following high-dose therapy and autologous stem cell transplantation.

Long-term clinical and molecular remissions in patients with mantle cell lymphoma (MCL) following high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) have been evaluated in only a few studies. Thirty-six patients with MCL received ASCT in our institution (27 patients undergoing first-line therapy, 8 patients undergoing second-line therapy, and 1 patient undergoing third-line therapy). In the case of long-term remission (≥5 years; n = 8), peripheral blood was tested for minimal residual disease (MRD) by t(11; 14) polymerase chain reaction (PCR) and immunoglobulin heavy-chain (IGH) PCR at the last follow-up. Ten-year overall survival (OS), progression-free survival (PFS), and freedom from progression (FFP) after first-line ASCT were 42 %, 43 %, and 54 %; after second-line ASCT, these were all 0 %. Four-year OS, PFS, and FFP for the first-line cohort were 75 %, 48 %, and 61 %, respectively. Four-year OS, PFS, and FFP after second-line ASCT were 55 %, 30 %, and 30 %, respectively. Treatment-related mortality (3 months after ASCT) was 0 %. The only prognostic factor for OS, PFS, and FFP was treatment line (p = 0.011, p = 0.046, and p = 0.023, respectively). No relapses occurred after 5 years following ASCT. So far, eight patients developed sustained long-term clinical and molecular complete remissions of up to 14.6 years following ASCT in the first treatment line. Sustained long-term clinical and molecular remissions can be achieved following ASCT in the first treatment line and apparently less frequent in the second treatment line.

[Late infectious complications after high-dose therapy and autologous blood stem cell transplantation]. / Späte infektiöse Komplikationen nach Hochdosistherapie und autologer Blutstammzelltransplantation.

AIM: Only a few data on frequency and character of late infectious complications after high-dose therapy (HDT) and autologous blood stem cell transplantation (ASCT) have been published. This prospective study was carried out to identify potential predictive factors for late infections (occurring after discharge following HDT) and to clarify the usefulness of prophylactic measures. PATIENTS AND METHODS: Clinical data of 192 consecutive patients treated with HDT and ASCT in a single hospital were analyzed on late infectious complications. After discharge following HDT, the 166 evaluable patients (84 with hematologic malignancies, 82 with solid tumors) had been examined and interviewed on infections every 4-12 weeks after ASCT. For Pneumocystis carinii prophylaxis, inhalation with pentamidine or oral cotrimoxazole was used for 3-4 months following ASCT. RESULTS: In the first 6 months following ASCT (after discharge) we saw on average one infectious episode per patient (median, range 0-6), usually light infections (mostly banal upper airway infections). 17 patients had to be treated in hospital for infectious (15 of whom with hematologic malignancies), three of whom (only with hematologic malignancies) died in spite of intensive care as a result of pneumonias due to opportunistic causative agents (mainly Pneumocystis carinii [PcP]). In the second half of the year after ASCT, five patients (with hematologic malignancies) had to be hospitalized due to infections. No further infection-related death occurred. Early documented infections (pneumonia, bacteremia or Clostridium difficile colitis) were associated with an increased risk for late serious infections. Zoster occurred in 18% of patients within 12 months, more frequently after increased pretreatment (25% vs. 11% after less pretreatment), most frequently in patients with relapsed lymphomas (32%). CONCLUSIONS: Significant late infectious complications after ASCT are uncommon. Patients with hematologic malignancies have a significantly increased risk of more serious infections and should be observed carefully. For risk patients with hematologic malignancies and possibly solid tumors, a strict PcP prophylaxis is required. Patients with relapsed lymphomas could possibly be treated preventively against zoster with low-dose aciclovir to reduce the extent of zoster disease. Each patient should be informed carefully that early signs of zoster require an effective zoster treatment as soon as possible.