Successful Autologous Peripheral Blood Stem Research Articles

Difficulties in the Diagnosis of Fibrinogen Aα-Chain Amyloidosis—Literature Review and Case Report of a Patient After Kidney Transplantation

Amyloidosis is a very heterogeneous disease. Correct diagnosis is extremely important because of the various treatment options for different types of amyloidosis. This study presents a case report and literature review of the misdiagnosis of fibrinogen Aα-chain amyloidosis (AFib amyloidosis). We report a 65-year-old man diagnosed with proteinuria in 2009. The kidney biopsy revealed the presence of Congo red-stained amyloid deposits. During differential diagnosis, amyloid deposits were discovered in adipose tissue and gingiva. Bone marrow trephine biopsy showed a predominance of lambda chains presenting plasmocytes. Based on performed medical examination, light chain amyloidosis was identified. Therefore, the patient received high-dose melphalan and underwent successful autologous peripheral blood stem cell transplantation. However, proteinuria, worsening of the kidneys' function, and incorrect levels of free light chains were still observed. In 2019, due to continuous treatment failure, a previously acquired kidney biopsy was examined by mass spectrometry, and numerous fibrinogen deposits were identified. Recommended DNA analysis revealed that the patient had AFib amyloidosis. Therefore, chemotherapy treatment was abandoned, and successful kidney transplantation was performed. Today, it is essential for medical practitioners to remember the possibility of rare and hereditary types of amyloidosis. There are multiple cases where a diagnosis was wrong or delayed because of the atypical course of the disease, the coexistence of another disease, and the rarity of AFib amyloidosis, and all of these reasons may result in the wrong treatment that will delay the right therapy. However, with the new, more precise diagnostics methods, such situations will become rare.

Successful autologous peripheral blood stem cell collection using large volume leukapheresis in patients with very low or undetectable peripheral blood CD34+ progenitor cells

Autologous stem cell transplantation provides some patients with hematolymphoid and solid organ malignancies an opportunity for cure. Management of peripheral hematopoietic stem cell (HSC) collections differs among institutions, especially if a very low pre-procedure peripheral blood CD34+ cell count (PBCD34) is demonstrated. This study retrospectively analyzed results of large-volume peripheral HSC collections in 91 patients over approximately two years. Fifteen patients with PBCD34 < 10 × 10e6/l (eleven with undetectable PBCD34) were compared to 76 patients with higher counts on the first collection day (adequate mobilizers). The poor mobilizer group had significantly lower pre-collection WBC and platelet counts as well as collection yields. However, most patients with PBCD34 < 10 × 10e6/l (80 %) collected the minimum target for HSC transplant (2.0 × 10e6 CD34+ cells/kg) in <5 consecutive days of collection, and those who did collect the minimum successfully underwent autologous transplantation, with hematopoietic engraftment and long-term survival comparable to the adequate mobilizers. Successful HSC collection may often be achieved regardless of d 1 PBCD34 counts.

Successful autologous peripheral blood stem cell harvest and transplantation after splenectomy in a patient with multiple myeloma with hereditary spherocytosis

Successful autologous peripheral blood stem cell harvest and transplantation after splenectomy in a patient with multiple myeloma with hereditary spherocytosis

Brisk Elevation of Serum Lactate Dehydrogenase During G-CSF Priming is a Significant Predictor for the Ensuing Successful Autologous Peripheral Blood Stem Cell Collection

Autologous stem cell transplantation plays a critical role in the management of patients with hematologic malignancies such as multiple myeloma and malignant lymphoma. The minimum number of CD34 positive cells required for transplantation is believed to be 2.0×106 cells/kg. Up to 20% of the patients, however, fail to reach the number after a single collection attempt and require multiple aphereses to obtain a sufficient number of stem cells. To predict the outcome of mobilization, several pre-mobilization factors have been investigated, including peripheral blood CD34+ cell count at the time of harvest, but little is as yet known about the significance of serum lactate dehydrogenase (LDH). We, therefore, sought to evaluate the predictive potential of serum LDH for the autologous stem cell yield. Peripheral blood stem cell mobilization attempts were made from April 2002 to March 2012 for 55 consecutive patients of hematologic disorders. Primary diagnosis of our patients and their mobilization chemotherapy regimens are shown in Table 1. All patient received G-CSF (filgrastim 400μg/sq/day or lenograstim 10μg/kg/day subcutaneously). None was mobilized with G-CSF alone. Aphereses were repeated until the total stem cell yield exceeded 2×106cells/kg, for maximum 3 consecutive days. Forty-four patients successfully produced the sufficient number of stem cells, while 11 patients failed (poor mobilizer). Between the two groups, there were no significant differences in pre-mobilization WBC counts and serum LDH levels. However, the ratio of the LDH level immediately before apheresis to the lowest one (“LDH-ratio”) were significantly lower in poor mobilizers than good mobilizers. Our ROC analysis showed that the cut-off value of “LDH-ratio” was 1.75. An elevation of serum LDH levels to reach “LDH-ratio”>1.75 were found to be a useful predictive factor for successful CD34+ stem cell collection. The delay in reaching “LDH-ratio”>1.75 may suggest that we should modify the mobilization regimen by, for instance, adding prelixafor.Table 1Pts’ characteristicsNo. of Patients55Median age (range)56(35-69)Gender, male (%)31(56)Primary Disease MM19 NHL26 HL4 Others6Median WBC counts ×103/μL (range)2.1(1.5-3.2)Median LDH Level IU/L (range)196(145-445)PBSC mobilization regimen ESHAP27 HD-CY22 G-CSF alone0 Others6MM indicates: multiple myeloma, NHL: non-hodgkin lymphoma, HL: hodgkin lymphoma, HD-CY: high dose cyclophosphamide Open table in a new tab MM indicates: multiple myeloma, NHL: non-hodgkin lymphoma, HL: hodgkin lymphoma, HD-CY: high dose cyclophosphamide

Successful Autologous Peripheral Blood Stem Cell Transplantation in 3 Women with POEMS Syndrome: A Single Centre Experience

Abstract 4504 INTRODUCTIONPOEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes) is a rare multi-system disease characterized by chronic progressive polyneuropathy and plasma-cell dyscrasia. A major diagnostic criterion for POEMS is elevation of circulating vascular endothelial growth factor (VEGF), which is believed to play a pathogenic role in this disease.We report 3 cases of POEMS syndrome treated with high-dose melphalan and autologous peripheral blood stem cell transplantation (PBSCT).PATIENTS AND METHODS CASE 1A 32-year-old woman presented with a progressive gait difficulty, weakness in limb muscles, skin hyperpigmentation, axillar and laterocervical lymphoadenopathies, peripheral edema. Neurophysiological testing showed a motor and sensory axonal polyneuropathy. At laboratory testing, thrombocytosis and monoclonal gammopathy IgA-λ were detected. A biopsy of laterocervical lymphonode was positive for Castleman's disease. Initial treatment with intravenous immunoglobulin (IVIg) failed to result in clinical benefit. After cyclophosphamide 2 g plus G-CSF priming a total of 7.1×106/kg stem cells were collected from peripheral blood and used to perform double autologous transplantation at interval of 5 months following conditioning with melphalan 140 mg/sq/m. CASE 2A 48-year-old woman presented with numbness and paresthesias in foot soles, weakness in lower limbs and axillar lymphoadenopathy. Nerve conduction studies showed motor and sensor demyelinating polyneuropathy. A monoclonal gammopathy IgG K-λ was present and bone marrow biopsy was unremarkable. She was treated with prednisone and plasma exchange with progressive improvement and clinical stabilization for two years. Unfortunately she presented a relapse of neurological symptoms responding to the same therapeutic strategy. A second relapse occurred after 3 months with appearance of sensory ataxia, xerotic skin, hepatomegaly. Laboratory analysis revealed biclonal gammopathy IgG k-λ and IgA-λ and Bence Jones proteinuria (λ light chain). Radiologic studies showed lytic lesions with sclerotic rim in homerus, VII rib and iliac bone and mediastinal, axillary and iliac lymphadenopathies. The patient received cyclophosphamide 2 g and G-CSF for mobilization. Melphalan 200 mg/sq/m was administered intravenously as conditioning regimen followed by reinjection of the cells collected. CASE 3A 44-year-old woman presented with asthenia, scleroderma-like skin changes, weight loss, limb paraesthesia and weakness. Neurophysiological testing showed a motor and sensor demyelinating polyneuropathy. She presented thrombocytosis and a monoclonal IgG-λ protein at laboratory tests. Radiologic studies showed laterocervical, axillary, mediastinal lymphoadenopathies, multiple thyroid nodules and a mixed sclerotic and lytic lesion in the pelvis and in the right humeral head. Biopsy of this lesion demonstrated a plasmacytoma with λ light chain restriction. Initial treatment with IVIg was unsuccesful. She received oral therapy with melphalan and prednisone for 3 years obtaining clinical stabilization, then she was treated with monthly zoledronic acid infusion only. After 3 years she presented a relapse of neurological symptoms, appearance of hepatomegaly, axillar and laterocervical lymph nodes enlargement, peripheral edema. She therefore underwent PBSC harvesting following cyclophophamide priming (2 g), than she received melphalan (200 mg/sq/m) with CD34-selected PBSC rescue. RESULTSThe post-transplant course was uneventful other than the development of febrile neutropenia in 2 cases. Patients 1 and 2 presented a progressive improvement in strength, physical skills and peripheral neuropathy after few months. They are well with clinical stabilization after 4 and 6 years, respectively, from PBSCT. At 3 months from PBSCT, patient 3 presents progressive neurological improvement and reduction of organomegalies. CONCLUSIONSAlthough treatment for POEMS is not standardized, disseminated disease require systemic therapy. No randomized controlled trials have been conducted, but patients with POEMS have been successfully treated with PBSCT since 1998. Our cases confirm its usefulness and safety and support the idea that, although delayed intervention maintains its efficacy, PBSCT could be considered early during the disease course to obtain the best response. Disclosures:No relevant conflicts of interest to declare.

Two Strategies of Stem Cells Mobilization Using Plerixafor and Comparison of Grafts Obtained with and without It. Is Plerixafor Only a Mobilization Agent?

Abstract 4385 Introduction:Successful autologous peripheral blood stem cell transplantation (aPBSCT) is critical for long-term survival and quality of life in patients with multiple myeloma (MM). Standard mobilization of PBSCs is in 15 to 20% of MM patients inefficient. Better mobilization response is achieved by adding plerixafor to current mobilization regimens. Based on studies it is possible to reduce these numbers to 2%. Methodology:During the period from 06/2009 to 08/2011 our department mobilized five patients with MM using plerixafor, of whom three were remobilized using standard G-CSF + plerixafor scheme (G+P) after a previous unsuccessful mobilization with cyclophosphamide + G-CSF (C+G). Two patients received plerixafor on demand in a failed first-line mobilization attempt (C+G+P).Comprehensive statistical analysis of products mobilized with plerixafor (8 products) versus products obtained using C+G regime alone (40 products) was performed comparing smears, colony forming-units (CFUs) and immunophenotype profile. Time to mobilization, pretreatment, used mobilization regime and adverse effects of plerixafor regimes were also analyzed. The ultimate goal of every mobilization - successful transplantation - was also described and analyzed comparing composition of transplanted products with engraftment of white blood cells (WBC), neutrophil granulocytes and platelets. Results:Analysis of the plerixafor group only:1. Both mobilization strategies (second-line G+P and first-line C+G+P) allowed to collect enough CD34+ cells for one (3 patients) or two (2 patients) transplants. Failure to mobilize using plerixafor has not been recorded. 3 patients successfully received transplants.2. Based on an analysis of risk factors for determining poor mobilizer 3 patients could be mobilized preemptively using G+P scheme preventing use of controversial cyclophosphamide.3. Adverse effects were mild and mainly related to G-CSF. In one patient mobilization was stopped after collecting 2.45 ×106/kg because of anxiety. However, we were unable to definitely connect anxiety symptoms to plerixafor.4. There was a statistically significant increase of leukocytes in peripheral blood observed after adding plerixafor. In 3 patients it allowed the CD34+ cells to rise above 20/μl.Comparative analysis of plerixafor group vs. group of patients mobilized with C+G:1. Duration of cytopenia after transplantation was comparable and statistically not different.2. Significantly higher numbers of CD19+ cells after plerixafor administration suggest a possible value of this drug in the treatment of diseases with this marker.3. Significant reduction of toxic granulation after plerixafor administration may be a proof of lesser number of infectious complications.4. Significantly lower numbers of younger cell forms and non-significantly higher numbers of mature cells in products mobilized with plerixafor prove a) no cytotoxic effect of plerixafor b) decreased regenerative potential of bone marrow in poor mobilizers even if chemotherapy is used.5. Significantly lower numbers of CD34+ cells and CFUs in plerixafor mobilized products suggest a worse overall mobilization response in this group. However CFUs have shown to predict stem cells yield better than CD34+ cells alone.6. The importance of a non-significant decrease in CD56+ cells in plerixafor mobilized products is unclear as co-expression of CD 38/56 does not show any differences. Conclusions:1. Preemptive first line mobilization with G+P seems to be an important strategy in predicted poor mobilizers which would otherwise be mobilized with C+G(+P). This prevents possible neutropenia and its complications. On demand first line G+P seems to be a good choice in patients that are mobilized with growth factors only as there is no risk of neutropenia.2. We highly recommend the investigation of CFUs which usually predict stem cells yield better than CD34+ cells alone and may allow transplantation even if CD34+ cells are low.3. Because aPBSCT is a therapeutic modality with clear benefit for patients with MM, we highly recommend the use of plerixafor in all MM patients where it is impossible to collect sufficient stem cells.According to our investigation, we believe that plerixafor is only starting its career as a mobilization drug. Its most valuable potential may be in curative regimens of diseases which have affinity to bone marrow. Disclosures:No relevant conflicts of interest to declare.

Successful Autologous Peripheral Blood Stem Cell Transplantation for Primary Cardiac Amyloidosis Patients with Heart Failure: Three Cases Report

Successful Autologous Peripheral Blood Stem Cell Transplantation for Primary Cardiac Amyloidosis Patients with Heart Failure: Three Cases Report

Relapse of polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome without increased level of vascular endothelial growth factor following successful autologous peripheral blood stem cell transplantation

We report a patient with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome who experienced relapse after successful treatment with autologous peripheral blood stem cell transplantation (auto-PBSCT). Interestingly, although vascular endothelial growth factor (VEGF) levels were positively correlated with disease activity before and after auto-PBSCT, as expected, levels did not increase at the time of relapse. The patient was treated with doxorubicin, dexamethasone, and diuretics, followed by thalidomide, and remains clinically stable at one year after treatment. This case suggests that VEGF level may not always be indicative of relapse of POEMS syndrome, and that thalidomide is both useful and safe for patients with relapse following successful treatment with auto-PBSCT.

Successful autologous peripheral blood stem cell transplantation with a double‐conditioning regimen for recurrent hepatoblastoma after liver transplantation

A four-yr-old boy developed a solitary metastasis nine months after living-related liver transplantation for unresectable hepatoblastoma. After resection of the metastatic lesion, he received an auto-PBSCT with a double-conditioning regimen consisting of melphalan and thiotepa. Auto-PBSCT could be safely performed without any serious regimen-related toxicity or infection. However, transient cessation of tacrolimus during myelosuppression resulted in graft rejection of the liver just after hematological engraftment, but rejection was resolved by tacrolimus and methylprednisolone. The patient is alive and free from disease two yr after auto-PBSCT without any signs of graft rejection. High-dose chemotherapy using this conditioning regimen may be feasible for recurrent hepatoblastoma after liver transplantation in terms of safety and anti-tumor activity.

Successful Autologous Peripheral Blood Stem Cell Transplantation for a Patient with Primary Adrenal Lymphoma with Hemophagocytic Syndrome

The adrenal glands are often an affected extranodal site in advanced non-Hodgkin lymphoma, but primary adrenal lymphoma (PAL) is extremely rare. Histologic examination of adrenal glands from patients with PAL reveals predominantly diffuse large B-cell lymphoma. Adrenal insufficiency is observed in about two thirds of patients. The prognosis of patients with PAL is poor: > 90% of patients die within 1 year of diagnosis, and long-term survivors are few. Effective therapeutic management of the condition has not been established. Herein, we report a 57-year-old man with PAL of diffuse large B-cell type that was later accompanied by hemophagocytic syndrome. He was initially treated with combination chemotherapy (1 cycle of CHOP [cyclophosphamide/doxorubicin/vincristine/prednisone] and 4 cycles of rituximab plus CHOP) and subsequently underwent autologous peripheral blood stem cell transplantation (auto-PBSCT) in his first complete remission. He has been well and disease free for 39 months since undergoing auto-PBSCT. The successful outcome of using auto-PBSCT in the treatment of a patient with PAL suggests that this therapeutic approach has value in treating this poor-prognostic disease.

Successful autologous peripheral blood stem cell transplantation in a Jehovah’s Witness with multiple myeloma: review of literature and recommendations for high-dose chemotherapy without support of allogeneic blood products

We present a case report of a successful high-dose melphalan therapy and autologous stem cell transplantation without the use of allogeneic blood product support in a 70-year-old patient suffering from multiple myeloma. Based on the experience in this case and thorough evaluation of the literature, we consider pre-transplant Hb level of 11-12 g/dl, platelet count higher than 70/nl, good WHO performance status of two and lower and informed consent as important eligibility criteria. During cytopenia recommended supportive measures include growth factor support with erythropoietin and G-CSF, p.o. iron treatment as well as prophylactic use of anti-fibrinloytic agents. Furthermore we discuss additional options that might be considered depending on the individual factors as e.g. pre-transplant collection and cryoconservation of autologous platelet concentrates. Moreover, an analysis of socio-economic issues regarding this procedure is presented. We conclude that allogeneic blood product free transplantation is a feasible procedure that can be offered to the patients belonging to distinct religious groups refusing allogeneic blood products as Jehovás Witnesses and patients presenting other contraindications for transfusions.

POEMS syndrome: relapse after successful autologous peripheral blood stem cell transplantation

We report a patient with POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes) treated with high dose chemotherapy and auto-Peripheral Blood Stem Cell Transplantation (auto-PBSCT) who had a very good response with complete clinical remission. Seven years later, she relapsed and a new sclerotic bone lesion was found. To our knowledge, this is the first POEMS syndrome relapse after successful auto-PBSCT.

Successful Autologous Peripheral Blood Stem Cell Transplantation Using Thiotepa in a Patient with Systemic Sclerosis and Cardiac Involvement

A 19-year-old man with systemic sclerosis (SSc) was hospitalized for autologous peripheral blood stem cell transplantation (auto-PBSCT) due to progressive scleroderma and cardiac involvement despite conventional treatment. During the administration of cyclophosphamide (60 mg/kg/day for 2 days) for mobilization and collection of CD34+ selected peripheral blood stem cells, he developed congestive heart failure. Echocardiogram showed hypokinetic asynergy from the septum to posterior wall, which might indicate underlying cardiac damage. We were also concerned about the risk of high-dose cyclophosphamide-induced cardiotoxicity. Since the dose-limiting toxicity of thiotepa, an alkylating agent, is myelosuppression, and cardiac toxicity due to thiotepa is less common, we used a conditioning regimen consisting of thiotepa (10 mg/kg/day, day -5) and low-dose cyclophosphamide (50 mg/kg/day, days -3 and -2), instead of the conventional high-dose cyclophosphamide (50 mg/kg/day x 4 days/course). The post-transplant course was uneventful, and the modified Rodnan skin thickness score improved from 32 to 15. The present case report demonstrates that thiotepa can be employed as a conditioning regimen for auto-PBSCT in SSc patients with cardiac involvement in order to reduce cyclophosphamide-induced cardiotoxicity.

Successful autologous peripheral blood stem cell harvest and transplant in a patient with cold agglutinins

Successful autologous peripheral blood stem cell harvest and transplant in a patient with cold agglutinins