Contribution of chemotherapy mobilization to disease control in multiple myeloma treated with autologous hematopoietic cell transplantation.

In patients with multiple myeloma (MM) undergoing autologous hematopoietic cell transplantation (auto-HCT), peripheral blood progenitor cells may be collected following mobilization with growth factor alone (GF) or cytotoxic chemotherapy plus GF (CC+GF). It is uncertain whether the method of mobilization affects post-transplant outcomes. We compared these mobilization strategies in a retrospective analysis of 968 patients with MM from the Center for International Blood and Marrow Transplant Research database who received an auto-HCT in the US and Canada between 2007 and 2012. The kinetics of neutrophil engraftment (⩾0.5 × 10(9)/L) was similar between groups (13 vs 13 days, P=0.69) while platelet engraftment (⩾20 × 10(9)/L) was slightly faster with CC+GF (19 vs 18 days, P=0.006). Adjusted 3-year PFS was 43% (95% confidence interval (CI) 38-48) in GF and 40% (95% CI 35-45) in CC+GF, P=0.33. Adjusted 3-year OS was 82% (95% CI 78-86) vs 80% (95% CI 75-84), P=0.43 and adjusted 5-year OS was 62% (95% CI 54-68) vs 60% (95% CI 52-67), P=0.76, for GF and CC+GF, respectively. We conclude that MM patients undergoing auto-HCT have similar outcomes irrespective of the method of mobilization and found no evidence that the addition of chemotherapy to mobilization contributes to disease control.

Alternative donors extend transplantation for patients with lymphoma who lack an HLA matched donor.

Alternative donor transplantation is increasingly used for high-risk lymphoma patients. We analyzed 1593 transplant recipients (2000-2010) and compared transplant outcomes in recipients of 8/8 allele HLA-A, -B, -C and DRB1 matched unrelated donors (MUDs; n=1176), 7/8 allele HLA mismatched unrelated donors (MMUDs; n=275) and umbilical cord blood donors (1 or 2 units UCB; n=142). Adjusted 3-year non-relapse mortality of MMUD (44%) was higher as compared with MUD (35%; P=0.004), but similar to UCB recipients (37%; P=0.19), although UCB had lower rates of neutrophil and platelet recovery compared with unrelated donor groups. With a median follow-up of 55 months, 3-year adjusted cumulative incidence of relapse was lower after MMUD compared with MUD (25% vs 33%, P=0.003) but similar between UCB and MUD (30% vs 33%; P=0.48). In multivariate analysis, UCB recipients had lower risks of acute and chronic GVHD compared with adult donor groups (UCB vs MUD: hazard ratio (HR)=0.68, P=0.05; HR=0.35; P<0.001). Adjusted 3-year OS was comparable (43% MUD, 37% MMUD and 41% UCB). These data highlight the observation that patients with lymphoma have acceptable survival after alternative donor transplantation. MMUD and UCB can extend the curative potential of allotransplant to patients who lack suitable HLA matched sibling or MUD.

Hematopoietic cell transplantation for primary plasma cell leukemia: results from the Center for International Blood and Marrow Transplant Research.

There are limited data on hematopoietic cell transplantation (HCT) in primary plasma cell leukemia (pPCL), an aggressive plasma cell disorder. We report outcomes of 147 patients with pPCL receiving autologous (n=97) or allogeneic (n=50) HCT within 18 months after diagnosis between 1995 and 2006. Median age was 56 years and 48 years for autologous HCT and allogeneic HCT, respectively. Progression-free survival (PFS) at 3 years was 34% (95% confidence interval (CI), 23-46%) in the autologous group and 20% (95% CI, 10-34%) in the allogeneic group. Cumulative incidence of relapse at 3 years was 61% (95% CI, 48-72%) in the autologous group and 38% (95% CI, 25-53%) in the allogeneic group. Overall survival (OS) at 3 years was 64% (95% CI, 52-75%) in the autologous group and 39% (95% CI, 26-54%) in the allogeneic group. Non-relapse mortality (NRM) at 3 years was 5% (95% CI, 1-11%) in the autologous group and 41% (95% CI, 28-56%) in the allogeneic group. The encouraging OS after autologous HCT, establishes the safety and feasibility of this consolidative treatment option after initial induction therapy for pPCL. Allogeneic HCT, although associated with a significantly lower relapse rate, carries a much higher risk of NRM and no OS benefit.

Update on desmoid tumors.

Desmoid tumors (DTs) are histologically benign proliferations of stromal cells but may grow locally aggressive. Overall, DTs are rare (0.03% of all neoplasms). A minority of DTs is associated with Gardner syndrome and mutations of the familial adenomatous polyposis (FAP) gene. Most spontaneous DTs are associated with mutations of the beta-catenin gene. This mutation results in the activation of Wnt/catenin signaling. Due to their variable clinical presentation and behavior, no standard approach for DTs can be recommended. In most cases of DTs of the extremities surgical extirpation is indicated, whereas in many other cases, a multimodal and multidisciplinary concept should be followed. In this review article, we discuss the diagnosis, pathogenesis, and treatment options for DTs, including targeted therapy with tyrosine kinase inhibitors.

[Unstable pertrochanteric femur fractures. Failure rate, lag screw sliding and outcome with extra- and intramedullary devices (PCCP, DHS and PFN)]. / Die instabile pertrochantäre Femurfraktur. Komplikationen, Fraktursinterung und Funktion nach extra- und intramedullärer Versorgung (PCCP, DHS und PFN).

AIM OF THE STUDY: The dynamic hip screw (DHS) often shows a high incidence of therapeutic failure and an impared outcome in the treatment of the unstable pertrochanteric femur fracture (31A2). Therefore often an intramedullary device is recommended. In a retrospective clinical study we examined whether the percutaneous compression plate (PCCP, Gotfried) provides advantages following unstable fractures in comparison to DHS and PFN. METHODS: From January 2002 to April 2007 135 patients with unstable pertrochanteric femur fractures underwent internal fixation with the PCCP (n = 46, age 78.3, ASA 2.8), DHS (n = 36, age 75.9, ASA 3.0) or PFN (n = 53, age 77.2, ASA 2.8). Radiological and clinical re-examination of the patients (33 PCCP, 24 DHS, 34 PFN) was performed 17 months later. RESULTS AND DISCUSSION: The PCCP was implanted in less time than the DHS and PFN (59 vs. 80 vs. 79 min, p = 0.004). Radiographic screening time was low (PCCP 143 vs. DHS 146 vs. PFN 280 s, p = 0.001). Re-operations for wound infections and haematomas occurred in 2 % after PCCP, 14 % after DHS and 4 % after PFN (p = 0.058). There was a low re-operation rate for fracture fixation complications in PCCP (9 %), in contrast to DHS (25 %) and PFN (13 %, p = 0.109). Cut-out was seen more in DHS (19 %, PCCP 2 %, PFN 4 %, p = 0.005). Lag screw sliding was high with DHS (PCCP 4 mm vs. DHS 9 mm vs. PFN 6 mm, p = 0.032). There was no correlation between lag screw sliding and outcome. PCCP, DHS and PFN had the same functional results in Merle d'Aubigné and Harris hip scores. CONCLUSIONS: Using the minimally invasive PCCP technique in unstable pertrochanteric femur fractures provides a promising therapy option especially with regard to surgical time, radiographic screening time and failure rate. Lag screw sliding was low. There was no advantage of the intramedullary device PFN.

[Surgical outcome in pertrochanteric femur fracture: the impact of osteoporosis. Comparison between DHS and percutaneous compression plate]. / Operationsergebnisse nach pertrochantärer Femurfraktur: Welchen Einfluss hat die Osteoporose? Vergleich zwischen DHS und perkutaner Kompressionsplatte.

AIM: The dynamic hip screw (DHS) often shows an impared outcome and a high incidence of therapeutic failure in patients with osteoporotic pertrochanteric femur fractures. This is caused predominantly by a fracture collapse and appears often in unstable fractures (31A2, 31A3). In a prospectively documented clinical study, we examined whether or not the percutaneous compression plate (PCCP, Gotfried) offers advantages following osteoporotic fractures. METHOD: From August 2003 to December 2005, 103 patients underwent internal fixation with the DHS (n = 40, age 76.1, ASA 2.9) or with the PCCP (n = 63, age 76.9, ASA 2.8). Proximal femurs were classified with the Singh grading system, which uses six grades of trabecular patterns to describe the degree of osteoporosis. Reexamination of the patients (27 DHS, 43 PCCP) was performed on average 18 months later. RESULTS: The PCCP was implanted into very osteoporotic femurs (Singh 2) in less time than the DHS (47 vs. 79 min). These patients treated with PCCP showed no difference in blood loss, but tended to have better outcomes (Merle d'Aubigné, Harris hip score) than those treated with DHS. Life quality, subjectively measured with the visual analogue score, was significantly better in the PCCP group with high-grade osteoporosis (Singh 2). The outcome after implantation of the PCCP was not correlated to the Singh index in stable or in unstable fractures. Mechanical complications occurred especially in unstable fractures (re-operation rate: DHS 4/18 [22 %], PCCP 3/29 [10 %], p = 0.266), without correlation to the Singh index. Excluding the avoidable complication of loosening of the screw-barrel portion, the re-operation rate for the PCCP was 3 % (cut-out: 1/29, p = 0.042) in unstable fractures. CONCLUSION: Use of the minimally invasive PCCP technique in osteoporotic pertrochanteric femur fractures provides an alternative to the dynamic hip screw, especially with regard to surgical time and outcome. Advantages occurred also in the re-operation rate following fracture fixation complications. The cut-out rate was significantly lower than in the DHS group in unstable fractures.

[Bilateral fracture of the femoral neck following transient osteoporosis in pregnancy]. / Beidseitige Schenkelhalsfraktur bei transienter Osteoporose während der Schwangerschaft.

During pregnancy changes of the bone metabolism can occur. Femoral neck fractures are known as a very rare consequence of transient osteoporosis in pregnancy. In a case report we present the clinical, radiological and histological features of a bilateral fracture of the femoral neck. A 29-year-old woman presented with pain in the right hip, which occurred in the 34 (th) week of pregnancy. The symptoms were initially interpreted as a sacroiliac joint affection and consequently a conservative treatment was initiated. Five days after a Caesarean section a dislocated fracture of the femoral neck was diagnosed on the left side. On the contralateral side the fracture was not dislocated. For therapy this patient underwent a total hip replacement on the left hand side and an internal fixation on the other side. Especially during pregnancy changes of the bone are diagnosed late due to the side effects of radiation. This case report indicates that MR imaging and other non-ionising techniques should be considered if such symptoms persist in spite of therapy.

Graft-versus-host and graft-versus-leukemia reactions: a summary of the Seventh International Symposium held in Garmisch-Partenkirchen, Germany, February 22nd-25th, 2006, Tolerance and Immunity, an update on lymphoid malignancies.

The Seventh International Symposium on graft-versus-host and graft-versus-leukemia reactions was held in Garmisch Partenkirchen (Germany, near Lake Riessersee) between January 22nd and 25th, 2006. A total of more than 100 invited participants (scientists and clinicians working in the area of allogeneic stem cell transplantation) discussed research in the area of lymphoid malignancies. Major topics of the 2006 meeting were lymphocyte biology, experimental systems, lymphoma pathogenesis, cellular therapy in vivo and vitro, idiotype-specific responses and graft-versus-malignancy reactions for lymphomas and multiple myeloma. Further highlights were immune responses to blasts of ALL, haploidentical transplantation, role of natural killer cells, clinical guidelines for allogeneic transplantation and adoptive immunotherapy in chronic lymphocytic leukemia and multiple myeloma, new antibody-mediated strategies. As can be seen in the summaries of the individual presentations, progress was made in the understanding of lymphoma biology and in the clinical application of graft-versus-lymphoma or graft-versus-myeloma effects. Each day was followed by round-table discussions, which summarized new data and challenged established concepts. The discussions resulted in new insights and projects for basic research and clinical transplantation.

Contribution of PET imaging to the initial staging and prognosis of patients with Hodgkin's disease.

BACKGROUND: Positron emission tomographic (PET) scanning utilizing [18F]fluorodeoxyglucose (FDG) is a new method of tumor imaging based on the increased glucose metabolic activity of malignant tumors. In Hodgkin's disease (HD), PET has proven value for the evaluation of residual masses following treatment and for the early diagnosis of relapse. In the initial staging of HD, PET frequently shows a higher stage than conventional methods (upstaging by PET). In the present study, we evaluated the frequency of stage changes by PET in a multicenter setting and determined its prognostic relevance. PATIENTS AND METHODS: A total of 73 patients with newly diagnosed HD were staged with both conventional methods and whole-body PET scanning. All histological types and stages were represented. The median time of follow-up after the initial diagnosis was 25 months (range 1 month to 5 years). The response to treatment was determined by standard clinical and diagnostic criteria. For the purpose of this analysis, data from a PET center associated with a university medical center and a PET center associated with a group oncology practice were combined. RESULTS: A total of 21 patients (28.8%) were upstaged by PET compared with conventional methods. In two cases (2.7%), a lower stage was suggested by PET scanning. With one possible exception, the upstaging had no obvious clinical or biological correlate. Among 12 patients in stage I (A + B) by conventional methods, seven were upstaged by PET (58.3%), four to stage II, one to stage III and two to stage IV. Among 42 patients in stage II, eight were upstaged by PET (19.0%), six to stage III and two to stage IV. Among 12 patients in stage III, six (50%) were upstaged to stage IV by PET. If only early-stage patients and major changes are considered (stages IA-IIB to III or IV), among 49, 10 were upstaged to III or IV, whereas in 39 staging was unchanged following PET. In the former group, three relapsed or were refractory compared with none in the latter group (P<0.006). In advanced stage patients (IIIA or IIIB) a trend toward treatment failure was apparent in patients who were upstaged by PET. CONCLUSIONS: PET scanning is an interesting new modality for the accurate staging of patients with HD and frequently shows a higher stage than conventional methods. PET should be performed at initial diagnosis and should be included in prospective studies of patients with HD. Upstaging by PET may represent a risk factor for a more advanced stage or a biologically more aggressive tumor. Patients with early-stage disease as identified by conventional methods have a significant risk of treatment failure if a more advanced stage is indicated by PET. At present, major stage changes suggested by PET imaging should be confirmed by an independent diagnostic method.

An update on graft-versus-host and graft-versus-leukemia reactions: a summary of the sixth International Symposium held in Schloss Ellmau, Germany, January 22-24, 2004.

The Sixth International Symposium on Graft-versus-Host and Graft-versus Leukemia Reactions was held in Schloss Ellmau (near Garmisch-Partenkirchen, Germany) between January 21 and 24, 2004. A total of 110 invited participants (scientists and clinicians working in the area of allogeneic stem cell transplantation) discussed current topics. Major topics of the 2004 meeting were: clinical results of donor lymphocyte infusions, basic biology, immunogenetics, function and clinical relevance of natural killer cells, haplo-identical stem cell transplantation, immune monitoring and immune modulation. Further highlights were: adoptive immunotherapy, vaccination and antibody-mediated strategies. As can be seen in the summaries of the individual presentations, important advances have occurred in our understanding of GVH and GVL reactions. Each session was followed by an animated discussion, which resulted in new ideas, insights and projects both for basic research and clinical transplantation. This year's symposium ('From Marrow Transplantation to Cell Therapy') was jointly organized by the Ludwigs-Maximilians-University of Munich (Sonderforschungsbereich 455), GSF (National Research Center for Environment and Health) and the EBMT Immunobiology Working Party. The organizers and authors of the conference proceedings would like to extend their gratitude to all participants for sharing their ideas, slides and manuscripts and making this event possible.

Treatment of advanced Hodgkin's disease with COPP/ABV/IMEP versus COPP/ABVD and consolidating radiotherapy: final results of the German Hodgkin's Lymphoma Study Group HD6 trial.

BACKGROUND: The purpose of this study was to compare the efficacy of the hybrid chemotherapeutic regimen COPP/ABV/IMEP (cyclophosphamide-vincristine-procarbazine-prednisone-doxorubicin-bleomycin-vinblastine-ifosfamide-methotrexate-etoposide) (CAI) with that of the standard regimen COPP/ABVD (COPP/ABV, dacarbacine) (CA) in the treatment of advanced-stage Hodgkin's disease (HD). PATIENTS AND METHODS: Between January 1988 and January 1993, 588 eligible patients with HD in stages IIIB and IV were randomly assigned to a treatment or control group. The treatment group received four cycles of CAI over a complete cycle duration of 43 days. The control group received four cycles of CA over 57 days. Both groups then received consolidating radiotherapy. RESULTS: Five hundred and eighty-four patients were suitable for arm comparison. Patients in each group were similar in age, sex, histological subtype and clinical risk factors. Complete remission rates, overall survival and freedom from treatment failure at 7 years were similar for the two groups: 77% versus 78%, 73% versus 73% and 54% versus 56% for CAI and CA, respectively. Differences in acute chemotherapy-related toxicity were significant, however. Prognostic factor analysis confirmed the relevance of the International Prognostic Index and revealed that stage IVB, low hemoglobin, low lymphocyte count, high age and male gender were associated with a poor prognosis CONCLUSION: The rapidly alternating hybrid CAI did not give superior results when compared with the standard regimen CA in advanced-stage HD.

New concepts about graft-versus-host and graft-versus-leukaemia-reactions. A summary of the 5th International Symposium held in Munich, 21 and 22 March 2002.

The Fifth International Symposium on Graft-versus-Host and Graft-versus-Leukemia Reactions was held on 21 and 22 March 2002 in the University Hospital (Klinikum Grosshadern) of the University of Munich. As in previous years, it was dedicated to the encounter of scientists and clinicians involved in hematopoietic cell transplantation. This year's symposium focused on the characterization of stem cells potentially expanding the use of hematopoietic stem cells and on gene therapy. The immunology section dealt with mechanisms of tolerance, and the characterization of minor histocompatibility antigens presented by major histocompatibility molecules. Further important topics were cytokines and dendritic cells. In 1 and 1/2 days of intense work, the invited speakers, chairmen, authors and an active audience experienced an exciting exchange of ideas and collaboration. Again, new impulses were given for basic research and clinical transplantation. The authors would like to express their deep appreciation and thanks to all participants of this symposium.

Monoclonal gammopathy after low-grade MALT lymphoma: evidence for a second neoplasm.

We report the case of a patient with lymphoma of the salivary gland, at first diagnosed as lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) but later found to infiltrate the bone marrow. At diagnosis, the patient had a polyclonal increase of gamma-globulins. Five years after initial diagnosis, the patient presented with monoclonal gammopathy and infiltration of the bone marrow with neoplastic cells. Initially, the patient had received chemotherapy with different protocols (including etoposide, cyclophosphamide, fludarabin, methotrexate, and vincristine), none of which induced a lasting response. Therapy with rituximab (chimeric anti-CD20 monoclonal antibody) finally led to partial remission. Eighteen months after rituximab, progressive lymphoma in the abdomen and a monoclonal gammopathy developed. The bone marrow showed infiltration by lymphoplasmacytoid cells (monoclonal expression of the light-chain type lambda, positive for CD20, heterogeneous expression of CD45). The patient achieved another short clinical response with 4 cycles of the CHOP-protocol, but soon the lymphoma progressed again. Five years and 8 months after the initial diagnosis, the patient died from septicemia and progressive lymphoma. By polymerase chain reaction (PCR) for the IgH gene it was shown that lymphoma cells were initially oligoclonal in the salivary gland and, later, biclonal in the bone marrow. Sequencing of two bands of apparently same length showed that these manifestations of lymphoma were not identical. Taken together, our data show that the initial low-grade oligoclonal MALT lymphoma was no longer present and a more aggressive biclonal lymphoma with plasmacytoid differentiation had developed. The new lymphoma was clonally distinct and produced high amounts of monoclonal IgG lambda by immunoelectrophoresis. The relationship of the second lymphoma to the initial MALT lymphoma is discussed.

[Treatment of osteoid osteoma: percutaneous procedure in comparison with open surgery]. / Behandlung des Osteoidosteoms: Perkutanes Ausbohren im Vergleich zur chirurgischen Resektion.

AIM: In recent years osteoid osteomas have been treated more frequently by means of percutaneous procedures. Several percutaneous techniques have been established. Our study presents the results which were obtained using a percutaneous drill system. In addition, a comparison between the results of the percutaneous procedure and the open surgical therapy is performed. METHOD: The retrospective study included patients with an osteoid osteoma who underwent percutaneous therapy or open surgery between 1992 and 2000. The following variables were addressed: age, gender, duration of complaints, localisation of the tumour, duration of hospital stay, size of the nidus, histology and recurrences. RESULTS: Of the total of 22 patients with an osteoid osteoma, 10 (45 %) were treated percutaneously and 12 (55 %) surgically. With regard to age, gender, and duration of complaints, the two groups were similar. Six (60 %) of the percutaneously treated patients sustained at least one recurrence. On the other hand, only one patient (8 %) of the surgically treated group experienced a recurrence. CONCLUSIONS: In comparison with recent studies presenting success rates in percutaneous treatment of osteoid osteomas between 77 and 100 percent, our own results are worse. One explanation for the low success rate might be the small drill size used.

Prospective study of clinical findings and changes in 56 Trilucent implant explantations.

Between 1995 and 1998 we implanted 88 Trilucent implants in 48 patients. The experience of 56 explantations in 30 patients are presented in this prospective study. Of 48 patients, 32 returned for review after we wrote to them. Twenty-seven elected to have their implants exchanged immediately for a fourth-generation cohesive silicon implant and three decided to have the implants removed and not replaced. In 14 patients it was clinically obvious that the volume of the implant had changed, although not all patients realized this. The absence of capsular contraction was notable (unanimously Baker II), so that most patients were asymptomatic and had to be convinced of the need for explantation. However, perioperatively, 55% of the implants had thickening or color change caused by the peroxidation of the triglyceride content. Typically the implant capsule was adherent to the surrounding tissues, especially pectoralis major. This prolonged operative time (184 min, on average) and hemostasis was a problem. During the study we developed a standardized operative technique, which enabled us to reduce operative times. Special attention had to be paid to the selection of the new implant volume, because many patients had become accustomed to the increase in the size of their breasts caused by the peroxidation of the implant content. Forty-three percent of patients preoperatively expressed the wish to have even bigger breasts than before. Nearly all of our patients at the three-month postoperative follow-up were happier with the new implants than before. It became apparent that after only two to three years there were obvious oxidative changes in the implants in asymptomatic patients. Based on our study result, the recommendations regarding explantation of Trilucent implants seem justified.

Laser blepharoplasty and periorbital laser skin resurfacing.

Standard blepharoplasty was developed in the early 1990s by minute descriptions of new anatomic details and surgical procedures derived from endoscopic surgery and by the introduction of lasers as cutting and ablative instruments. The combination of these innovations with deep frontotemporal and mid-facial lifting has added a new dimension to periorbital rejuvenation. This contribution deals with the role of lasers within the scope of expanded periorbital surgery. Indications and surgical techniques of standard and extended laser-assisted blepharoplasties are described. For upper lid blepharoplasty, the CO(2) laser is compared as a cutting instrument to the radiosurgical microelectrode needle. In performing a lower lid blepharoplasty different options are given to choose a minimal invasive transconjunctival approach in combination with laser skin resurfacing or to perform a standard transcutaneous dissection but using the laser for cutting only. With increasing anatomic and surgical knowledge as well as refinements of instruments, it has become evident that the surgeon must define clear positions when to take advantage of these new procedures. Therefore, pros and cons of standard and laser-assisted blepharoplasties will be discussed.

Different types of human leukemias express the message for TNF-alpha and interleukin-10.

Leukemic cells proliferate under the influence of cytokines. In particular, the colony-stimulating factors stimulate the growth and proliferation of myeloid leukemia cells. Under normal conditions, tumor necrosis factor-alpha (TNF-alpha) is produced by activated monocytes, whereas interleukin- 10 (IL-10) is produced by several cell types like monocytes and lymphocytes. The autocrine production of cytokines by leukemic cells may have a pathogenic role in the progression of leukemia or may be an epiphenomenon. In this study, we investigated the expression of TNF-alpha and IL-10 in human leukemic cells by RT-PCR and by a cytoplasmic protein assay. Most cases of acute myelogenous leukemia (AML) (7/8 cases) and all cases of acute lymphoblastic leukemia (ALL) (n = 2), chronic myelogenous leukemia (CML) (n = 5), both in chronic phase and during blast crisis, expressed the mRNA for TNF-alpha and IL-10. A patient whose blasts were positive for IL-10 and negative for TNF-alpha, had high circulating levels of IL-10 and failed to respond to donor lymphocyte infusions. Using a cytoplasmic protein assay, generally low levels of cytoplasmic TNF-alpha and IL-10 were found which increased in case of TNF-alpha following stimulation with lipopolysaccharide. Taken together, our data show that most leukemic cells express the mRNA for a proinflammatory cytokine (TNF-alpha) and an immunosuppressive cytokine (IL-10). More work is necessary to determine under which conditions these cytokines actually paralyze the immune system and thereby permit the progression of leukemia.

Levels of insulin-like growth factor after stem cell transplantation.

Some cytokines, i.e. tumor necrosis factor-, interleukin-6 and soluble interleukin-2 receptors are associated with complications of stem cell transplantation. Insulin-like growth factors (IGFs) are a family of peptides essential for the proliferation of normal and malignant cells. Recently increased levels of IGFs have been associated with the development of malignant tumors. In this communication we report on 96 measurements of insulin-like growth factor-I (IGF-1), insulin-like growth factor-II (IGF-2), and insulin-like growth factor-binding protein-3 (IGFBP-3) performed in 19 patients following stem cell transplants. Seventeen patients had allogeneic and 2 patients autologous transplants. Most IGF determinations were made at days 0, 7, 14, 21 and 28, some at other time points. The baseline values (day 0) of IGF-1 and IGFBP-3 were not different from controls. IGF-2 values were slightly lower than controls. Following transplantation, a consistent increase of IGF-1 was observed in 9/16 patients at days 7 and 14. Later the values decreased again. IGF-2 and IGFBP-3 did not change significantly after transplantation. No direct correlation could be established with the severity of graft-versus-host disease, levels of interleukin-6 and the time to hematopoietic recovery. A potential relevance of IGFs following stem cell transplantation may be the early diagnosis of liver damage and the development of second malignancies. More studies are necessary to investigate the pathophysiology and the clinical relevance of the increase of IGF-1 following stem cell transplantation.

Advanced head and neck cancer: long-term results of chemo-radiotherapy, complications and induction of second malignancies.

BACKGROUND: Chemo-radiotherapy is superior to radiotherapy alone in the treatment of advanced, inoperable head and neck cancer. The long-term treatment results, the induction of second malignant tumors, and other long-term toxicities are not well defined. PATIENTS AND METHODS: 100 consecutive patients with advanced head and neck cancer who were treated at our center were studied. Treatment results, survival, the occurrence of late complications, and second malignant tumors (SMT) were investigated. 78 patients were treated with a protocol combining cisplatinum, 5-fluorouracil, folinic acid and hyperfractionated irradiation. 22 patients were treated with other chemo-radiotherapy protocols. The relative risk of developing an SMT was compared with that within the normal population. RESULTS: The cumulative total probability of survival was 51.1% at 2 years and 38.7% at 4 years. The probability of relapse-free survival was 39.9% at 2 years and 36.7% at 4 years. A total of 7 patients developed SMT (4 cases of lung cancer, 2 colon cancers, 1 skin cancer). After 6 years, a cumulative risk of SMT of 8.7% was observed. The relative risk of developing an SMT was significantly increased (4.45-fold in males) compared with a normal population. 13 of 38 evaluable patients (34.2%) had severe late complications like fibrosis of soft tissues, nerve lesions, or were dependent on tracheal cannulas. CONCLUSIONS: The treatment results and long-term prognoses in our population of unselected high-risk patients are unsatisfactory, but comparable to those from multicenter studies. About 35% of patients become long-term (> 4 years) survivors. SMT generally occur early, have a poor prognosis and, most likely, are not treatment-related. Approximately 30% of long-term survivors have severe, often incapacitating late effects. The treatment and - if possible - prevention of these late effects is important for the quality of life of patients who survived advanced head and neck cancer.