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Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, often affecting extranodal sites like the stomach. While R-CHOP chemotherapy is the standard treatment, some patients fail to respond, requiring alternative approaches. In this report, we describe a case of gastric DLBCL in a 68-year-old man who became resistant to R-CHOP but achieved remission with R-DHAP. Case Report: A 68-year-old man came to the hospital with symptoms of persistent indigestion. After undergoing an endoscopic biopsy in October 2020, he was diagnosed with high-grade gastric diffuse large B-cell lymphoma. A PET-CT scan revealed a large mass in his stomach. He started R-CHOP chemotherapy, completing eight cycles. However, after five cycles, imaging showed remaining disease in the stomach, along with new lesions in the left lung. Despite ongoing treatment, a biopsy after the sixth cycle confirmed that the lymphoma was still active. The situation worsened—his disease had become resistant to R-CHOP. In response, his treatment shifted to R-DHAP chemotherapy. After just two cycles, an endoscopic biopsy revealed no active lymphoma, and only signs of chronic atrophic gastritis remained. PET-CT scans over the following months showed no recurrence of lymphoma. However, in March 2023, a PET-CT showed some hypermetabolic lymph nodes in the cervical region, but these had regressed significantly compared to previous scans. As of October 2024, the patient continues to be closely monitored and remains asymptomatic. Discussion: This case highlights the challenges faced when dealing with chemotherapy-resistant DLBCL. It emphasizes the need to pivot quickly to alternative therapies, like R-DHAP, when first-line treatments fail. The successful response in this patient demonstrates that adjusting treatment strategies can make a significant difference in outcomes. Additionally, it shows the importance of long-term follow-up, especially with extranodal lymphomas, where the risk of relapse is ongoing.

Abstract Burkitt leukemia (BL) represents a highly aggressive lymphoma characterized by proliferation rates of around 100%, and a frequent spread into the central nervous system. If standard frontline chemotherapy fails, the prognosis is usually dismal, and reports on successful effective salvage therapy strategies for patients with relapsed/refractory BL are scant. Here, we report on a 40‐year‐old female patient who suffered an early relapse of BL three months after the completion of frontline chemoimmunotherapy. Strikingly, after only one cycle of R‐DHAP chemotherapy, the patient showed CR of BL enabling swift transition to a consolidating allogeneic stem cell transplantation. A 40‐year‐old previously healthy woman presented to the hospital with fatigue and incessant epistaxis, and a diagnosis of BL was made upon histological examination of a bone marrow biopsy. Treatment was initiated according to the GMALL 2002 B‐NHL/ALL protocol, which could induce complete molecular remission. Nevertheless, three months after chemotherapy, the patient exhibited BL relapse in the bone marrow, and on Fluorodeoxyglucose (FDG)–PET‐imaging. The relapse therapy was started with R‐DHAP, and after only one cycle, the patient once again entered complete remission (CR) paving the way for allogeneic stem cell transplantation. Unfortunately, the patient again relapsed five months after transplantation prompting salvage therapy with R‐DHAC and the execution of the second stem cell transplantation. However, one month after the second transplantation the patient presented with chemorefractory meningeosis leukemia resulting in the initiation of palliative care treatment. In summary, we report on rapid CR of relapsed BL after a single cycle of rituximab‐DHAP. Given a paucity of clinical trials on the treatment of patients with r/r BL, we intend to highlight the potential efficacy of rituximab‐DHAP as salvage therapy in those patients.

Simple Summary: Patients with relapsing/refractory B-cell lymphoma who respond to a platinum salt-based salvage regimen can be cured after therapy intensification followed by autologous stem cell transplantation. The Bruton tyrosine kinase inhibitor ibrutinib, given alone or in association with other molecules, has proven effective in numerous B-cell lymphomas. The aim of the current study was to evaluate the safety of the combination of ibrutinib, rituximab, dexamethasone, and cytarabine with either cisplatin (R-DHAP) or oxaliplatin (R-DHAOx), with ibrutinib given based on a prespecified dose-escalation design. The concomitant combination of ibrutinib and R-DHAP resulted in limiting hematological, infectious, and renal toxicities. As a result, the maximum ibrutinib dose could not be administered. On the other hand, when the ibrutinib administration schedule was combined with R-DHAOx, ibrutinib dosing could be increased up to the maximum prespecified dose but with relevant toxicities. Despite a strong rationale for combining ibrutinib with either R-DHAP or R-DHAP/Ox, this approach was limited by significant toxicities. In the post-rituximab era, patients with relapsed/refractory non-Hodgkin B-cell lymphoma (R/R B-NHL) responding to a platinum salt-based salvage regimen can potentially be cured after intensification followed by autologous stem cell transplantation, with the quality of the response to salvage predicting survival. The Bruton tyrosine kinase inhibitor ibrutinib, given as monotherapy or combined with other molecules, has proven effective in numerous B-cell lymphomas. To evaluate the safety of the combination of ibrutinib, rituximab, dexamethasone, and cytarabine with either cisplatin (R-DHAP) or oxaliplatin (R-DHAOx), we conducted a multicenter Phase 1b-II study in transplant-eligible R/R B-NHL patients, with ibrutinib given using a 3-by-3 dose-escalation design. The combination of R-DHAP and ibrutinib (given from Day 1 to Day 21 of each cycle) was associated with dose-limiting hematological, infectious, and renal toxicities, while we were unable to reach a dose to recommend for Phase II. R-DHAOx could only be combined with a daily dosage of 280 mg ibrutinib when administered continuously. R-DHAP combined with intermittent ibrutinib administration (from Day 5 to Day 18) was found to be highly toxic. On the other hand, when this administration schedule was combined with R-DHAOx, ibrutinib dosing could be increased up to 560 mg but with relevant toxicities. Despite a strong rationale for combining ibrutinib and R-DHAP/R-DHAOx, as both target lymphoma B-cells by different mechanisms, this approach was limited by significant toxicities. [ABSTRACT FROM AUTHOR]

Aim. To evaluate the efficiency of the R-DA-EPOCH-21 + R-DHAP protocol and autologous hematopoietic stem cell transplantation (a BEAM conditioning mode) in first-line therapy for primary mediastinal large B-cell lymphoma (PMBCL). Subjects and methods. In 2013 to 2016, the investigation enrolled 57 patients with newly diagnosed PMBCL (according to the 2008 WHO criteria). The results were analyzed in 40 patients who had completed their treatment. Results. All the 40 patients (14 men and 26 women) (median age, 27 years (19 to 67 years)) received 6 cycles of polychemotherapy (PCT) in accordance with the R-DA-EPOCH-21 regimen. After induction PCT cycles, 32/40 (80%) patients achieved complete remission. Partial remission was stated in 8/40 (20%) patients who had further 2 cycles of chemotherapy using the R-DHAP program and autologous hematopoietic stem cell transplantation (a BEAM conditioning mode). Two-year overall and relapse-free survival rates were 100% and 96%, respectively; the median follow-up was 17 months. Conclusion. The R-DA-EPOCH regimen allows complete remission in 80% of the cases and two-year survival in 100%. If there are unfavorable factors at onset and in partial remission, it is appropriate to intensify treatment at early stages, by using high-dose chemotherapy and autologous hematopoietic stem transplantation.

In patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL), R-DHAP (rituximab, dexamethasone, cytarabine, and cisplatin) is a commonly used regimen for salvage therapy and for mobilization of peripheral blood stem cells (PBSCs). At our center, a modified R-DHAP regimen with administration of 25 mg/m 2 cisplatin as a 3-hour infusion over 4 consecutive days, instead of a single infusion of 100 mg/m 2 over 24 hours, has been established. The aim of this study was to analyze the efficiency of this modified R-DHAP regimen plus G-CSF as a mobilization strategy. We retrospectively analyzed clinical characteristics, PBSC collection and autologous stem cell transplantation parameters, and hematologic reconstitution data for 65 patients with relapsed or refractory DLBCL who underwent PBSC collection after mobilization with the modified R-DHAP protocol at our institution between 2002 and 2013. Data were evaluated for the overall cohort and with regard to the number of R-DHAP cycles received before PBSC collection. PBSC collection was performed after the first R-DHAP course in 32 patients (49%), after the second course in 30 patients (46%), and after the third course in 3 patients (5%). Sixty-three patients (97%) achieved the collection goal of ≥2.0 × 10 6 CD34 + cells/kg body weight. A significantly higher median CD34 + cell collection yield was achieved when cells were collected after the first R-DHAP course compared with after the second course ( P < .01). A peripheral blood leukocyte increase of ≥1.0 × 10 9 /L and a platelet increase of ≥20 × 10 9 /L were observed by 11 days after ASCT. In our cohort, the modified R-DHAP regimen proved safe and feasible, showed an overall response rate (complete response, complete response unconfirmed, and partial response) of 66%, and allowed efficient mobilization of CD34 + cells for PBSC collection. [ABSTRACT FROM AUTHOR]

Background: Rituximab (R) in combination with DHAP is a widely accepted salvage regimen for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). A common adverse effect of this protocol is renal toxicity which may result in treatment discontinuation. Assuming that a lower single dose of cisplatin over several days would reduce renal toxicity, our institution has chosen to administer cisplatin in a dosage of 25 mg/m(2) per day as a 3-h infusion over 4 consecutive days.Methods: In this study, we analyzed the renal function of 122 patients with relapsed or refractory DLBCL treated with R-DHAP at our institution. Overall, 256 R-DHAP cycles were administered. 31 (25%), 61 (50%), 14 (12%) and 16 (13%) patients received one, two, three or four R-DHAP courses, respectively.Results: A glomerular filtration rate (GFR) decrease was observed after each R-DHAP cycle. However, in none of the subgroups the median GFR was lower than 60 ml/min/1.73 m(2). In most patients, only renal impairment stage I and II was observed. Renal impairment stage III was seen in 10% and stage IV only in 1% of patients.Conclusion: We conclude that a modified R-DHAP regimen with administration of cisplatin 25 mg/m(2) over 4 consecutive cycles leads only to minimal renal toxicity. [ABSTRACT FROM AUTHOR]

Diffuse large B cell primary hepatic lymphoma is a rare disease with limited available information regarding treatment strategy. Although the liver contains lymphoid tissue and is an important site for lymphocytes activation, primary hepatic lymphoma is rare. Host factors make the liver a poor environment for malignant lymphoma development. Its coexistence with human immunodeficiency virus (HIV) infection increases morbidity and mortality risks. Additionally, jaundice increases chances of developing adverse effects from chemotherapy. Here, we report a case of diffuse large B cell primary hepatic lymphoma in a 32-year-old HIV positive man. Due to elevated liver enzyme levels and jaundice, the patient was initially treated with an R-DHAP regimen, which was replaced with an R-CHOP regimen. Restaging images with a positron emission tomography scan after the latest chemotherapy cycle confirmed remission. This is the first report of complete remission of primary hepatic diffuse large B cell lymphoma in an HIV positive patient in the English literature.