Blood Stem Cell Transplantation Research Articles

Successful neoadjuvant synchronous chemo- and radiotherapy for disseminated primary intracranial choriocarcinoma: case report

We report a 17-year-old male with disseminated intracranial choriocarcinoma at the basal ganglia whose consciousness level was very low at diagnosis. He received neoadjuvant therapy (NAT) consisting of combined chemo- and radiotherapy prior to radical excision of the tumor. Postoperatively he was treated with three courses of high-dose chemotherapy (carboplatin (CBDCA), methotrexate (MTX), and etoposide (VP-16)) and peripheral blood stem-cell transplantation. This combination of therapies resulted in tumor regression on MRI and remarkable improvement in his neurological condition. Ours is the first report of the effectiveness of NAT followed by radical surgery in a patient with disseminated primary intracranial choriocarcinoma.

Hematopoietic stem cell therapy for malignant diseases

Allogeneic bone marrow or blood stem cell transplantation (SCT) has changed its face in the last two decades. The introduction of nonmyeloablative conditioning regimens has reduced procedure toxicity and allowed the application of SCT in patients and conditions in which SCT was not offered in the past. In this review we will summarize the changes and accomplishments achieved in the past years in the field of stem cell transplantation for malignant disorders.

Ex vivo expansion of umbilical cord blood stem cells for transplantation: growing knowledge from the hematopoietic niche

Umbilical cord blood transplantation (UCBT) in adults is limited by the small number of primitive hematopoietic stem cells (HSC) in each graft, resulting in delayed engraftment post transplant, and both short- and long-term infectious complications. Initial efforts to expand UCB progenitors ex vivo have resulted in expansion of mature rather than immature HSC, confounded by the inability to accurately and reliably measure long-term reconstituting cells. Ex vivo expansion of UCB HSC has failed to improve engraftment because of resulting defects that promote apoptosis, disrupt marrow homing and initiate cell cycling. Here we discuss the future of ex vivo expansion, which we suggest will include the isolation of immature hematopoietic progenitors on the basis of function rather than surface phenotype and will employ both cytokines and stroma to maintain and expand the stem cell niche. We suggest that ex vivo expansion could be enhanced by manipulating newly discovered signaling pathways (Notch, Wnt, bone morphogenetic protein 4 and Tie2/angiopoietin-1) and intracellular mediators (phosphatase and tensin homolog and glycogen synthase kinase-3) in a manner that promotes HSC expansion with less differentiation. Improved methods for ex vivo expansion will make UCBT available to more patients, decrease engraftment times and allow more rapid immune reconstitution post transplant.

Disappearance of Minimal Residual DEK-CAN Fusion Transcript after Allogenic Hematopoietic Stem Cell Transplantation in a Child with t(6;9) Acute Myeloid Leukemia.

Chromosomal translocation t(6;9) (p23;q34) associates with acute myeloid leukemia (AML), although that is found in less than 2% of all cytogenetic events in children with AML. Recent molecular analysis of patients with t(6;9) (p23;q34) has demonstrated a rearrangement of the genes DEK and CAN resulting in the formation of a chimeric DEK-CAN mRNA. The prognosis of patients with t(6;9) is thought tobe very poor, because of poor response to chemotherapy and/or high relapse rate. However, recent reports showed that allogeneic hematopoietic stem cell transplantation may have a potential to improve the prognosis of patients with t(6;9). We report here we were able to monitor DEK-CAN fusion transcripts in the serial points along chemotherapy courses and hematopoietic stem cell transplantation in a child with t(6;9). A 5-yaer-old Japanese boy diagnosed as having AML (M5b). Chromosomal analysis revealed t(6;9)(p23:q34), and real-time quantitative polymerase chain reaction (RQ-PCR) revealed positive chimeric DEK-CAN mRNA. After diagnosis, he received an induction chemotherapy. At the end of the induction chemotherapy, he was in a hematological and cytogenetic complete remission (CR), however DEK-CAN fusion transcript was still positive. After completion of five courses of consolidation therapy, he was in hematological and cytogenetic CR, although molecular minimal residual disease (MRD) was still positive. So he received allogeneic peripheral blood stem cell (PBSC) transplantation from 1 locus mismatched father. Busulfan and Melpharan were used for conditioning regimen. Cyclosoprin A and short course of methotrexate were emplyed for the prophylaxis of graft-versus-host disease (GVHD). Engraftment of PBSC was achieved at day 15. He had mild acute GVHD and no clonic GVHD. Bone marrow analysis at the time of engraftment revealed hematological, cytogenetic, and molecular CR. Now he is still in a persistent molecular negativity of DEK-CAN fusion transcript by RQ-PCR and keeps event-free survival for five years after PBSCT. The monitoring of DEK-CAN fusion transcript in the chemotherapies was reported from some investigators. However, there were very few reports about the monitoring DEK-CAN fusion transcripts before and after hematopoietic stem cell transplantations. In coclusion, we succeeded to exclude DEK-CAN fusioin transcript after hematopoietic stem cell transplantation in a child with t(6;9) AML. We conclude that DEK-CAN molecular monitoring by RQ-PCR in is a useful tool for the management of patients with t(6;9) AML.

Palifermin Treatment in Patients Receiving High Dose Melphalan or BEAM Prior to Autologous Peripheral Blood Stem-Cell Transplantation.

Background. Oral mucositis (OM) is a common complication of high-dose (HD) chemotherapy conditioning regimens used with peripheral blood stem-cell transplantation (PBSCT). Severe grades of OM are associated with higher morbidity such as infections, need for total parenteral nutrition (TPN), opioid analgesics and prolonged hospitalization and has been historically underreported. Recent epidemiology reveals an incidence of severe OM of 50–60%. Moreover, OM is reported by patients as the worst and most debilitating complication of PBSCT. The keratinocyte growth factor, palifermin, stimulates the growth, differentiation, migration, and survival of epithelial cells. Palifermin is now approved in the US and the EU to decrease the incidence, duration, and severity of OM in patients (pts) with hematological malignancies requiring autologous PBSCT.Objective. This report describes the treatment of 60 pts who received palifermin through an early access program in Belgium. We evaluated the effect of palifermin on OM in pts with multiple myeloma or non-Hodgkin's lymphoma receiving HD melphalan (HD Mel) or BEAM conditioning regimen, respectively, prior to autologous PBSCT.Methods. The pts received palifermin (IV bolus: 60 μg/kg/day) for 3 days before and 3 days after HD Mel or BEAM. The common OM prevention strategy included basic oral hygiene, mouth washes and oral cryotherapy during HDM administration (n=9). For each patient, follow-up data were collected on mucositis grading, duration of hospitalization, neutropenic fever, treatment with G-CSF, IV antibiotics, opioids, and TPN. The grade of OM during treatment was assessed according to the WHO oral-toxicity scale (grade 0 to 4). Drug-related adverse events were also recorded.Results. Thirty pts received HD Mel and 30 pts received BEAM before PBSCT. All 60 pts received at least 3 palifermin bolus injections; the scheduled doses (6 bolus) were administered to 55 (91%) of 60 pts. Analysis of the follow-up data revealed that 10 (16%) pts experienced no OM. Furthermore, a low incidence (31%) of severe (grade 3 and 4) OM was observed with each conditioning regimen. The median duration of severe OM with the HD Mel regimen was 7 days (range 3–27) contrasting with a median OM duration of 3 days (range 2–12) with the BEAM regimen. Two pts in each regimen required prolonged hospitalization due to OM. With either regimen, neutropenic fever and use of IV antibiotics were common (70% of pts), while bacteremia was infrequent (20% of pts). Myeloid growth factors were administered post PBSCT to the majority of pts. Forty percent (40%) of HD Mel-treated pts and 26% of BEAM-treated pts required opioid analgesics. The percentages of pts receiving TPN were similar in the 2 conditioning regimens (66% of all pts). TPN was used in 16 (84%) pts with severe OM and in 24 (58%) pts with no or grade 1–2 OM. Adverse events clearly related to palifermin were reported in 25 (41%) of 60 pts. The most common adverse events included rash (18 events, 8 severe), disorders of tongue and oral mucosa (13 events, 2 severe), edema (10, no severe) and pruritus (7, no severe).Conclusions. These results indicate that palifermin use prior to HD Mel or BEAM and immediately following the transplantion may provide effective support in the prophylaxis of severe OM in pts undergoing autologous PBSCT, without major toxicity.

Retrospective analysis of psychological state in leukemia patients after a success of the transplantation of blood stem cell

目的 探讨白血病患者造血干细胞移植成功后的心理状态,以便为其心理治疗提供理论指导.方法 应用焦虑自评量表(self-rating anxiety scale,SAS)、抑郁自评量表(self depression scale,SDS)评价了32例白血病患者造血干细胞移植成功后第2年、第3年和第5年3个不同时期内的焦虑症状和抑郁症状发生情况,并用单项社会支持度调查表(the single-item measure of social support,SIMSS)分析了社会支持对患者产生焦虑症状和抑郁症状的影响.结果 大部分白血病患者的焦虑症状和抑郁症状主要发生在移植成功后2年内,以后逐渐减少;随着疾病的康复,虽然焦虑症状和抑郁症状的发生率逐渐降低,但总与低社会支持度相关.结论 对白血病患者应加强心理疏导,尤其在移植后2年内。

Primary cutaneous histiocyte and neutrophil‐rich CD30+ and CD56+ anaplastic large‐cell lymphoma with prominent angioinvasion and nerve involvement in the forehead and scalp of an immunocompetent woman

Cutaneous lymphomas co-expressing CD56 and CD30 are very rare. They share a clinicopathological overlap with natural killer- (NK)/T-cell lymphomas and anaplastic large-cell lymphomas (ALCLs), two entities with widely disparate clinical behavior. We present a case of an immunocompetent 57-year-old Caucasian woman with a rapidly growing, angiodestructive and neuroinvasive primary cutaneous ALCL (PCALCL). The neoplastic population of large anaplastic CD30+ and CD56+ T cells was masked by a massive admixture of histiocytes and neutrophils. The partially ulcerated and pus-secreting tumor involved the forehead and scalp and was assessed as clinical stage IAE. After chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone), the patient achieved a complete remission. Additionally, high-dose chemotherapy with autologous peripheral blood stem-cell transplantation was administered as a consolidation of complete remission, in which she has remained for 6 years. This is the first CD30+ and CD56+ primary skin lymphoma to be reported on the head. The presented case carries a remarkable combination of clinicopathological features of PCALCL and NK-/T-cell lymphoma.

Fatal Clostridium difficile-associated toxic megacolon following unrelated stem-cell transplantation

BACKGROUND: Nosocomial Clostridium difficile-associated colitis occurs in 1–4 % of surgical patients. In 3–5 %, it may progress to toxic megacolon (TM) and severe sepsis, requiring surgical intervention. METHODS: Case report. RESULTS: A patient suffering from neutropenia following peripheral blood stem-cell transplantation for acute lymphatic leucemia developed TM despite therapy with Metronidazol and oral Vancomycin. Ultimately she underwent right sided and subsequently subtotal colectomy. After successful treatment of TM the patient died later from multiorgan failure in the course of prolonged neutropenia. CONCLUSIONS: Patients with expected prolonged neutropenia who develop toxic megacolon should undergo subtotal colectomy without delay as they seem not to be able to control the infection even when receiving appropriate antibiotic therapy.

Alemtuzumab As Consolidation After a Response to Fludarabine Is Effective in Purging Residual Disease in Patients With Chronic Lymphocytic Leukemia

Treatment with alemtuzumab has resulted in negative responses for minimal residual disease (MRD) in patients with chronic lymphocytic leukemia (CLL). In a prior analysis we demonstrated that it is possible to achieved MRD negativity, as assessed by polyclonality of immunoglobulin heavy chain after consolidation with alemtuzumab. This phase II study evaluated 34 patients with CLL who received alemtuzumab consolidation in an effort to improve the quality of their response to fludarabine-based induction. Subsequent peripheral blood stem-cell (PBSC) collection and transplantation, tolerability, and pharmacokinetics also were assessed. Thirty-four patients younger than 65 years who had a clinical response to fludarabine-based induction therapy received alemtuzumab 10 mg subcutaneously three times per week for 6 weeks. PBSCs were collected after mobilization with cytarabine and granulocyte colony-stimulating factor. Blood samples for pharmacokinetics study were taken between days 1 and 31. The complete response rate improved from 35% after fludarabine induction to 79.4% after alemtuzumab consolidation, including 19 patients (56%) who achieved MRD negativity. The most common adverse events were injection-site reactions and fever. Cytomegalovirus reactivation occurred in 18 patients, all of whom were successfully treated with oral ganciclovir. PBSC collection was successful in 24 (92%) of 26 patients, and 18 patients underwent autologous PBSC transplantation. Alemtuzumab plasma concentrations increased gradually during the first 2 weeks and accumulated more rapidly thereafter. Subcutaneously administered alemtuzumab was effective, safe, and well tolerated as consolidation therapy in patients with CLL who responded to fludarabine induction therapy. Subsequent PBSCT was feasible thereafter.

The combination of cyclophosphomide, thalidomide and dexamethasone is an effective alternative to cyclophosphamide – vincristine – doxorubicin – methylprednisolone as induction chemotherapy prior to autologous transplantation for multiple myeloma: a case-matched analysis

A retrospective case-matched study was conducted to compare the oral regimen CTD (cyclophosphamide – thalidomide – dexamethasone) and infusional CVAMP (cyclophosphamide – vincristine – doxorubicin – methylprednisolone) as induction therapy followed by autologous peripheral blood stem-cell transplantation (PBSCT) for newly diagnosed multiple myeloma patients. The response rate after three cycles of treatment was statistically higher with CTD (n = 27) compared to CVAMP (n = 27) (89% vs. 56%, P = 0.016). Toxicity studies showed more neutropenia (grade 3/4) (4% vs. 60%, P = 0.0002) with CVAMP and more thrombotic episodes with CTD (11% vs. 4%). CTD may emerge as the superior induction regimen prior to PBSCT, in terms of high efficacy and better tolerability.

43 Infections complicating unrelated donor cord blood stem-cell transplantation (CBST): 281 Episodes in recipients of 100 CBST at a comprehensive cancer center (1996–2005)

43 Infections complicating unrelated donor cord blood stem-cell transplantation (CBST): 281 Episodes in recipients of 100 CBST at a comprehensive cancer center (1996–2005)

Tandem high-dose chemotherapy supported by autologous peripheral blood stem-cell transplantation and radiotherapy for recurrent malignant fibrous histiocytoma

Malignant fibrous histiocytoma (MFH) is a soft-tissue sarcoma created from fibroblast cells and characterized by a high rate of metastasis or recurrence with poor prognosis. We report a case of initially well differentiated (G1) MFH of the trunk in a 33-year-old woman. Two years after primary diagnosis, metastases were found in the lung, trunk, gluteus region, upper extremities and brain. Histopathological findings indicated a stromal tumor consisting of spindle cells, and immunohistochemical examination of resected specimens established the definite diagnosis of poorly differentiated MFH (G3). Initial surgery of several solid tumors on the trunk, lung and extremities was performed. There was a high local recurrence and metastasis rate, and the patient was treated with radiotherapy and conventional chemotherapy followed by tandem high-dose chemotherapy and peripheral blood stem-cell transplantation. She is currently well seven years after the transplant, with no signs of metastasis and recurrence. We review the clinical picture of the tumor in this patient and discuss its diagnosis, pathogenesis and treatment.

Molecular Monitoring of Residual Disease in Patients with Mantle Cell Lymphoma and CLL after Allogeneic Bone Marrow Transplantation Post Reduced Intensity Conditioning.

To control circulating lymphoma cells after allogeneic transplantation in order to induce or manipulate graft-versus-lymphoma (GvL) reactivity in case of relapse, molecular monitoring of circulating lymphoma cells was carried out by quantitative real-time PCR for clone-specific IgH(CDR3) sequences on six patients (CLL n=3; mantle cell lymphoma (MCL) n=2; variant hairy cell leukaemia (vHCL) n=1). All patients were considered as high risk for recurrence or relapse because of age, refractory disease, failure after autografting or poor performance status. They had at least one or more high-risk features that precluded the application of a standard myeloablative conditioning regimen. Therefore, they were treated with allogeneic blood stem cell transplantation (BSCT) from unrelated donors after toxicity-reduced conditioning with treosulfan and fludarabine. Molecular relapse was defined as an increase of circulating lymphoma cells by more than three orders of magnitude in the absence of symptoms or signs of clinical relapse.In the three patients with CLL and one MCL patient leukemic cells disappeared from peripheral blood and bone marrow within the first six months after transplant as demonstrated by quantitative PCR. Only short periods of acute GvHD were observed and successfully treated. In 2/6 patients (one with vHCL and one with MCL) a molecular relapse was detected one month (MCL) and 6 months (vHCL) after transplant. A 3-log increase of circulating lymphoma cells was observed within about 20 days (MCL) and 3 months (vHCL) starting from <1 lymphoma cell/500,000 cells to about 1,000 lymphoma cells/100,000 cells. Rapid reduction and withdrawal of immunosuppressive therapy combined with the infusion of the monoclonal antibody rituximab led to the disappearance of circulating lymphoma cells in both patients. It has to be emphasized that in both patients with documented molecular relapse rituximab alone or in combination with chemotherapy has not led to a stable CR or molecular remission before allogeneic BSCT. The disappearance of recurrent lymphoma cells in both patients correlated well with the development of acute GvHD. This fact demonstrates the curing potency of GvL. Serial molecular monitoring at short-term intervals provided the additional important information that further therapeutic interventions, c.f. infusion of donor lymphocytes, were not necessary. All patients monitored are still in continuous complete clinical and molecular remission for almost three years.Clinical relapse of malignant B cell lymphoma after allogeneic BSCT can be successfully treated by immune therapeutic intervention, e.g. reduction and rapid withdrawal of immunosuppression and infusions of peripheral blood lymphocytes from the original blood stem cell donor by establishing graft versus lymphoma (GvL) reactions. In addition, B-cell specific monoclonal antibodies seem to be very helpful for treating relapses. These therapeutic interventions may be even more effective when introduced before clinical relapse, possibly already at molecular relapse detected by quantitative real time PCR. Therefore, molecular monitoring by quantitative real-time PCR carried out at ≤ 3 months intervals may further improve transplant results and the long-term outcome of patients treated within clinical studies.

High-Dose Therapy and Autologous Blood Stem-Cell Transplantation Compared With Conventional Treatment in Myeloma Patients Aged 55 to 65 Years: Long-Term Results of a Randomized Control Trial From the Group Myelome-Autogreffe

To study the impact of high-dose therapy (HDT) with autologous stem-cell support in patients with symptomatic multiple myeloma (MM) between the ages of 55 and 65 years. One hundred ninety patients between 55 and 65 years old who had newly diagnosed stage II or III MM were randomly assigned to receive either conventional chemotherapy (CCT; ie, monthly courses of a regimen of vincristine, melphalan, cyclophosphamide, and prednisone) or HDT and autologous blood stem-cell transplantation (using either melphalan alone 200 mg/m(2) intravenous [IV] or melphalan 140 mg/m(2) IV plus busulfan 16 mg/kg orally as pretransplantation cytoreduction). Within a median follow-up of 120 months, median event-free survival (EFS) times were 25 and 19 months in the HDT and CCT groups, respectively. Median overall survival (OS) time was 47.8 months in the HDT group compared with 47.6 months in the CCT group. A trend to better EFS (P = .07) was observed in favor of HDT, whereas OS curves were not statistically different (P = .91). The period of time without symptoms, treatment, and treatment toxicity (TwiSTT) was significantly longer for the HDT patients than for the CCT patients (P = .03). With a median follow-up time of approximately 10 years, this randomized trial confirmed a benefit of HDT in terms of EFS and TwiSTT but did not provide evidence for superiority of HDT over CCT in OS of patients aged 55 to 65 years with symptomatic newly diagnosed MM.

Double-Cycle, High-Dose Ifosfamide, Carboplatin, and Etoposide Followed by Peripheral Blood Stem-Cell Transplantation for Small Cell Lung Cancer

To determine the tolerability and feasibility of double-cycle, high-dose chemotherapy followed by peripheral blood stem-cell transplantation (PBSCT) after conventional chemotherapy or chemoradiotherapy for small cell lung cancer (SCLC). Patients with previously untreated SCLC received two cycles of cisplatin, 80 mg/m2, and etoposide, 300 mg/m2 (cisplatin-etoposide [PE]). Later, they were administered high-dose etoposide, 1,500 mg/m2, followed by granulocyte colony-stimulating factor for collection of peripheral blood stem cells. After two additional cycles of PE, the patients received high-dose ifosfamide, 10 g/m2, carboplatin, 1,200 mg/m2, and etoposide, 1,000 mg/m2 (ifosfamide-carboplatin-etoposide [ICE]) followed by PBSCT twice at 3-month to 4-month intervals. Patients with limited disease (LD) concurrently received 50 Gy of irradiation with the last two cycles of PE. Eighteen patients, including 11 patients with LD, were enrolled. Fifteen patients could receive high-dose ICE followed by PBSCT twice, and 3 patients could receive it once. The median number of CD34+ cells collected was 13.11 x 10(6)/kg. The median numbers of days to neutrophil counts > or = 500/microL and platelet counts > or = 50,000/microL were 10 days and 14.5 days after the first PBSCT, and 10 days and 15 days after the second PBSCT, respectively. Grade 3 diarrhea occurred in one cycle, and grade 3 renal toxicity occurred in two cycles. The overall response rate was 100%, with an 83.3% rate of complete or near-complete response. The 2-year and 5-year survival rates were 72% and 55% in patients with LD and 43% and 0% in patients with extensive disease, respectively. Double-cycle, high-dose ICE therapy followed by PBSCT is tolerable and feasible even after conventional chemotherapy or chemoradiotherapy in patients with SCLC.

Long‐term remission of blastic natural killer‐cell lymphoma after autologous peripheral blood stem‐cell transplantation

We report here a case of blastic natural killer (NK)-cell lymphoma treated successfully with autologous peripheral blood stem-cell transplantation (APBSCT). A 57-year-old man had skin tumors and was diagnosed as having blastic NK-cell lymphoma by tumor biopsy. Skin, lymph nodes, left tonsil, and bone marrow were involved at presentation. Chemotherapy led to complete remission (CR). To sustain CR, the patient underwent high-dose chemotherapy in combination with 12 Gy of total-body irradiation (TBI) followed by autologous peripheral blood stem-cell rescue. He showed rapid recovery of hematopoiesis and could tolerate regimen-related toxicity after APBSCT. He has maintained long-term remission for 20 months after APBSCT. From this case, we concluded that APBSCT with preconditioning by TBI-containing regimens might be a cure-attaining treatment for disseminated blastic NK-cell lymphoma and should be considered as a choice of treatment in cases where no suitable donors for allogeneic transplantation are available.

Function of the hypothalamic–pituitary–gonadal axis in long-term survivors of hematopoietic stem cell transplantation for hematological diseases

Gonadal dysfunction in adult long-term survivors of hematopoietic stem cell transplantation (HSCT) is an adverse effect of conditioning regimens consisting of chemotherapy and total body irradiation (TBI). The impact of conditioning regimens consisting of chemotherapy alone on the function of the hypothalamic–pituitary–gonadal (HPG) axis was evaluated in a series of 41 female and 31 male patients who had undergone either autologous or allogeneic bone marrow/peripheral blood stem cell transplantation; mean age at transplantation was 32.6 years and mean time interval from transplantation was 1.5 years (range 0.2–9.8 years). Provocative testing of the HPG axis by administration of luteinizing hormone-releasing hormone was included in the first endocrinological evaluation. The follow-up period extended to three consecutive years. Gonadal dysfunction was not reported by any of the patients prior to their underlying illness. Hypergonadotrophic hypogonadism was observed in 97% of female and 19% of male patients. Leydig cell strain (normal testosterone, high luteinizing hormone levels) was evident in 32% and spermatogenesis damage (high follicle-stimulating hormone levels) in 68% of the male population. At the conclusion of the study four women (10%) had regained spontaneous menses and all hypogonadal men had resumed normal testosterone levels. Our results indicate a high incidence of gonadal dysfunction due to target organ failure in HSCT recipients not treated by TBI.

Superiority of thalidomide and dexamethasone over vincristine-doxorubicindexamethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma

The aim of the present study was to compare thalidomide-dexamethasone (Thal-Dex) and vincristine-doxorubicin-dexamethasone (VAD) as primary therapy in preparation for autologous peripheral blood stem-cell (PBSC) transplantation for multiple myeloma (MM). For this purpose, we performed a retrospective matched case-control analysis of 200 patients who entered 2 consecutive studies from 1996 to 2004 and received Thal-Dex (n = 100) or VAD (n = 100) administered for 4 months before collection of PBSCs and autologous transplantation. Matching criteria included age, clinical stage, and serum beta2-microglobulin levels. In comparison with VAD, Thal-Dex resulted in a significantly higher response rate (52% versus 76%, respectively; P < .001) and effected more profound reduction in myeloma cell mass of both immunoglobulin G (IgG; P = .02) and IgA (P = .03) type. More frequent toxicities included nonfatal deep vein thrombosis with Thal-Dex (15%) and granulocytopenia with VAD (12%). In each of the 2 treatment groups, 91% of patients proceeded to PBSC mobilization. The median number of collected CD34+ cells was 7.85 x 10(6)/kg in the Thal-Dex group and 10.5 x 10(6)/kg in the control group. Thal-Dex may be considered an effective and relatively well-tolerated oral alternative to the more complex VAD regimen as front-line therapy for MM patients who are candidates for subsequent autologous transplantation.

Risk Factors for Bronchiolitis Obliterans in Allogeneic Hematopoietic Stem-Cell Transplantation for Leukemia

Reported risk factors for bronchiolitis obliterans (BO) in allogeneic hematopoietic stem-cell transplant recipients come from modest-sized studies and are limited to experiences of single institutions. We sought to identify risk factors for BO using data from the International Bone Marrow Transplant Registry. Registry data on 6,275 adult patients with leukemia who received human leukocyte antigen-identical sibling transplants from 1989 to 1997 and survived at least 100 days after transplantation were evaluated for the study. Risk factors for BO were analyzed using proportional hazards regression. Seventy-six patients were found to have BO, with an incidence rate of 1.7% at 2 years after transplantation. The Kaplan-Meier estimate of median time to onset of BO was 431 days. Histologic evaluation was performed in 36 patients (47%). In 28 patients (37%), diagnosis was based on pulmonary function tests, CT scans of the chest, or a combination of both. On multivariate analysis, the factors that were associated with an increased risk for BO included the following: peripheral blood-derived stem cell, a busulfan-based conditioning regimen, interval from diagnosis to transplant > or = 14 months, female donor to male recipient sex match, prior interstitial pneumonitis, and an episode of moderate-to-severe acute graft-vs-host disease (GVHD). In addition to corroborating previously reported risk factors, such as acute GVHD and a busulfan-based conditioning regimen, we found that peripheral blood stem-cell transplantation, long duration to transplant, female donor to male recipient, and a prior episode of interstitial pneumonitis are associated with an increased risk for BO.

Successful hematopoietic stem‐cell transplantation in multicentric Castleman disease complicated by POEMS syndrome

A 39-year-old male presented with pedal edema, pleural effusion, splenomegaly, and generalized lymphadenopathy. Serum protein electrophoresis demonstrated the presence of a monoclonal protein. Histological examination of the spleen following splenectomy showed multifocal vascular proliferation and angiovascular lesions consistent with multicentric Castleman disease. He was treated with steroids and rituximab, but without improvement. The patient was found to have portal venous thrombosis and lower extremity arterial thrombosis. He then received combination chemotherapy with cyclophosphamide and mitoxantrone but developed a severe inflammatory polyneuropathy that left him disabled and wheelchair-bound. A diagnosis of multicentric Castleman disease with POEMS syndrome was made, and he then received high-dose chemotherapy with melphalan followed by autologous peripheral blood stem-cell transplantation. Following transplantation, his nerve conduction studies improved and his serum protein electrophoresis normalized. He is currently ambulatory and does not need wheelchair assistance. Hematopoietic stem-cell transplantation may be a treatment option for patients with multicentric Castleman disease and POEMS syndrome.