Splenectomy as a measure to treat prolonged post-transplant cytopenia associated with hypersplenism

Splenectomy has been used in the past to shorten myeloid recovery following hematopoietic SCT (HSCT). Indeed, patients with myelofibrosis, chronic myelogeneous leukemia and other myeloproliferative disorders have more rapid myeloid recovery when a splenectomy is performed prior to HSCT.1, 2, 3, 4, 5, 6, 7 Also, having splenomegaly at the time of transplant has been associated with delayed platelet and neutrophil engraftment.5, 7 However, splenectomy has fallen out of favor because of the use of reduced intensity conditioning, PBSC source and growth factors, all of which shorten the duration of cytopenias post transplant. Studies have also showed no apparent survival benefit with splenectomy before transplant.3, 4, 6, 7 Still, splenectomy is recommended prior to HSCT in select patients with massive splenomegaly for alleviation of severe pain and shorten the duration of myeloid recovery following the transplant.7 In this report, we propose another potential indication for splenectomy in transplant recipients. Two HSCT recipients with prolonged post transplant cytopenias due to poor graft function and/or hypersplenism achieved normal blood counts following splenectomy with no short-term or long-term adverse consequences. Patient A, a 68-year-old male with stage IV mantle cell lymphoma (MCL) and splenic involvement, underwent an autologous peripheral blood HSCT following myeloablative total body radiation (1200 cGy given in six fractions) and high dose CY at 60 mg/kg/day for 2 days. He received 2.3 × 106 CD34+cells/kg. Prior to HSCT, the patient’s relapsed MCL was in PR following six cycles of FCM-R (fludarabine, CY, mitoxantrone and rituximab) regimen. His early post transplant course was complicated by herpes zoster infection, which responded to antiviral therapy. He was discharged on day +13 after presumed myeloid recovery with ANC being greater than 2000. However, the patient remained anemic and persistently thrombocytopenic requiring transfusions. His WBC remained at a low-normal range with ANC greater than 500/mL. On day +28, his Hb was still 9.0 and platelet count was 24 000. Restaging studies on day +73 did not show any recurrent disease, but he had persistent massive splenomegaly by PET-CT. BM examination showed hypercellularity (60–70% cellularity) with left-shifted myeloid maturation. No lymphoma was seen by morphology, immunochemistry nor by flow cytometer. His symptomatic anemia and thrombocytopenia persisted at the same level until day +112 when he underwent a laparoscopic splenectomy. On pathologic examination, the spleen measured 15 × 10.5 × 3.5 cm with histological indications of focal old hemorrhage and fibrosis, without lymphoma infiltration. A sharp increase in blood count was observed immediately after the splenectomy (Figure 1A), and he achieved durable count recovery within 3 days post-splenectomy. No perioperative nor postoperative complications were observed. His blood counts remained within normal range until he died of recurrent lymphoma 3 years later. Patient B is a 26-year-old male with CML that evolved into ALL with circulating blasts and CNS involvement when he was evaluated in our center. Following induction chemotherapy given in conjunction with dasatinib followed by intrathecal Ara-C and cranio-spinal radiation therapy, the patient achieved remission and then underwent a matched related allogeneic peripheral blood HSCT after TBI-Melphalan conditioning. He received 4.2 × 106 CD34+ cells/kg. At the time of transplant, he had massive splenomegaly extending about 6 cm below the costal margin. A CT scan showed splenic lesions with unclear etiology. The patient’s post transplant course was complicated by skin and gut graft-versus-host disease, which responded to systemic methylprednisolone. At the time of discharge on day +25, the patient’s Hb, WBC and platelet count were 10.8 g/dL, 3.1 K/mcL and 36 K/mcL, respectively. The patient remained pancytopenic. The cause of his persistent cytopenia was felt to be secondary to hypersplenism. Another concern was possible residual leukemia in the spleen and the risk for relapse. On day +139, his WBC, Hb and platelet counts were 1.5 K/mcL, 10.9 g/dL and 28 000 K/mcL, respectively. He underwent a laparoscopic splenectomy through the lateral approach on day +179 post transplant. After the splenectomy, on day +203 post transplant, the patient’s WBC, Hb, hematocrit and platelet counts were 16.8 K/mcL, 12.9 g/dL, 43.1% and 530 K/mcL, respectively (Figure 1B). The spleen specimen was negative for residual acute lymphocytic leukemia but showed markedly congested red pulp with increased granulocytes. His subsequent course was remarkable for chronic GVHD. He is currently alive 3 years and 9 months after his transplant and 3 years and 3 months after splenectomy with normal blood counts. Occasionally, transplant recipients may experience prolonged pancytopenia due to a variety of reasons including poor graft function, residual disease, drug induced myelosuppression, infections and active GVHD. Another potential cause is hypersplenism in patients with palpable splenomegaly going into transplant. Hypersplenism can be compensated in most cases by robust hematopoietic activity in the BM. However, patients who have sluggish hematopoietic recovery due to either damaged BM microenvironment and/or low numbers of stem cells infused as shown in poor mobilizers may experience chronic symptomatic cytopenia requiring intermittent transfusions in some cases. Even in the case of full engraftment and normal graft function, splenomegaly itself is associated with delayed engraftment.7 There are no effective treatment options for these patients when they become symptomatic requiring transfusion. Therefore, it is not unreasonable to assert the potential benefit of splenectomy in select HSCT recipients. Splenectomy done before transplant has been demonstrated in previous studies to facilitate engraftment following HSCT in patients with myeloproliferative disorders.1, 2, 3, 4, 6, 7 The data on the clinical benefit of post transplant splenectomy, however, is limited to a few case reports.8, 9, 10 Additional reports may substantiate the potential utility of splenectomy to improve cytopenias in select HSCT recipients. In addition to hematologic improvement, splenectomy may potentially reduce tumor burden and consequently the risk of relapse. We decided on splenectomy in the second case not only to treat his chronic cytopenia but also to diagnose and reduce the risk of relapse because of the lesions seen in the CT scan before his transplant. We have not observed any short or long-term adverse events following the splenectomy in these cases. The blood loss was minimal and no prolonged hospitalizations occurred. Splenectomy is a relatively safe procedure with advanced techniques such as laparoscopy having less than a 5% procedure-related mortality.11 The positive clinical outcome we have observed in these two cases suggests that splenectomy may normalize blood counts in transplant patients with hypersplenism symptoms and related cytopenia persisting post transplant. The authors declare no conflict of interest.